Factors predicting Cosmesis (CA), Late effects (LE) and Patient reported outcome measures (PROM) in high-risk breast cancer (BC) treated with hypo-fractionated radiotherapy (HF-WBI): real world outcomes from a developing country

Factors predicting Cosmesis (CA), Late effects (LE) and Patient reported outcome measures (PROM) in high-risk breast cancer (BC) treated with hypo-fractionated radiotherapy (HF-WBI): real world outcomes from a developing country | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Factors predicting Cosmesis (CA), Late effects (LE) and Patient reported outcome measures (PROM) in high-risk breast cancer (BC) treated with hypo-fractionated radiotherapy (HF-WBI): real world outcomes from a developing country Chandrashekhar Mishra#, Sushma Agrawal#, Punita Lal#, Gyan Chand, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3836655/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Introduction : Literature on cosmesis in large operable (LO) and locally advanced breast cancer (LABC) is sparse, so we investigated the cosmesis, LE and PROM and factors affecting it in this subset. Materials and Methods : BC with upfront BCS or after neoadjuvant chemotherapy (NACT) underwent physical CA, LE and PROM using EORTC, RTOG and BR23 questionnaire respectively. Patient, tumour and treatment related factors were correlated with CA, LE and PROM by univariate and multivariate analysis. Results: 186 women underwent BCS, but only 82 could participate due to Covid. Prevalence of high-risk features were found: >3cm tumour in 37%, 50% node positive, 100% received CT, grade 3 in 57%, Her-2/TNBC in 70%. At a median follow-up of 5 years, we found that 56% patients had adverse global cosmesis. Factors responsible for adverse cosmesis were tumour size [> 3 cm, HR 2.3], node positivity [HR 0.3], receipt of CT [HR 6.5], large resection volumes [HR 4.6], large breast volume [HR 1], supraclavicular RT in 43% [HR 0.7]. Dosimetric factors found significant for adverse cosmesis were breast volume receiving 107% dose (> than 10cc, HR 5) and breast volume receiving 100% dose (> than 120cc, HR 5). The incidence of arm oedema was 6%, shoulder stiffness 20%, brachial plexopathy 4% and factors significant for LE were tumour size > 3cm [HR 9], breast volume receiving 107% [HR 6], and co-morbidity [HR 3]. 69% had poor body image, 35% breast pain, 47% were sexually active. Conclusion: BC with LO/LABC and high-risk features had adverse cosmesis in 56% women. large operable locally advanced breast cancer Brest conservation cosmesis late effects patient reported outcome measures Figures Figure 1 Figure 2 Figure 3 Introduction BCS is the standard of care in early breast cancer and LO disease adequately down-staged with chemotherapy (CT) which is followed by whole breast radiotherapy and boost to the resection cavity. Results from large randomized trials have confirmed that hypo-fractionated whole-breast irradiation (HF-WBI) is safe and efficacious in comparison to conventional fractionation in early-stage breast cancer [1,2]. Moreover, the recent update of the American Society of Radiation Oncology (ASTRO) evidence-based guidelines on radiation therapy for the whole breast confirmed that HF-WBI represents the preferred option for patients with early-stage breast cancer, regardless of age, chemotherapy administration and breast size and recommends minimization of breast volume receiving >105% of the prescription dose [3]. Real world data have confirmed the safety and efficacy of hypo-fractionated RT in early BC and LABC in various studies [4,5]. Cosmesis is an important endpoint of successful implementation of breast conservation. While the reported cosmesis with HF-WBI is good in early BC, there is sparse literature on the cosmesis and late-effects in with LO/LABC. In our country, women more often present with LO/LABC [6]. Though we have reported the safety and efficacy of HF-WBI in LO/LABC, cosmetic outcome and late-effects analysis had not yet been conducted [5]. Hence we conducted a cross-sectional study of women who underwent BCS during a 5 year period with at least 3 years follow-up, to ascertain the CA and LE in arm and shoulder and PROM. Materials and Methods After approval of institute ethics committee (2018-82-IP-EXP), all patients of BC who underwent BCS during the period 2013 to 2017 and who could attend the clinic for cosmesis and LE assessment for arm and shoulder were enrolled in this study. Women underwent upfront BCS in those who were suitable, while large operable and locally advanced tumours underwent BCS after adequate downstaging with standard neoadjuvant chemotherapy. All were treated with HF-WBI whole breast RT and supraclavicular RT (in node positive) by 3DCRT technique to a dose of 40 Gy/15 fractions in 3 weeks followed by boost (10 Gy/4–5 fractions) to tumour bed. IMRT (field in field technique) was used when necessary to improve homogeneity of target volume coverage. All hormone receptor positive patients received either tamoxifen or letrozole according to their menopausal status and trastuzumab was administered to Her-2 neu positive women. Two physicians (SA and CM) together assessed cosmesis (CA) and LE using the EORTC and RTOG scoring system respectively. Patient reported outcome measures (PROM) was collected with EORTC-BR23 questionnaire. Data and statistical analysis The ‘‘quite a bit” and ‘‘very much” categories of all endpoints of CA, LE and PROM were combined into one category (moderate/marked), similarly none and a little were combined into another category (mild) which resulted in a 2-point scale. Logistic regression was used to assess the effect of all the tumour and treatment variables on the risk of cosmesis, late-effects and PROMs. Each factor was first tested alone in a univariate model, and then significant factors were tested in a multivariate analysis to test whether the effects were independent of each other. A value of p = 0.05 was taken as significant. Analysis of PROM using BR23 was used as stated in the questionnaire. The raw scores obtained from the questionnaire were linearly transformed to a 0–100 range. Results Out of 186 patients who underwent BCS followed by HF-WBI (2013-17), only 86 patients could attend OPD for cosmesis and LE assessment due to Covid. Four among these underwent APBI (accelerated partial breast radiation) so they were excluded from the analysis to ensure data of a homogenously treated population. The cause of non-enrollment of 100 patients in this study were: change in contact number (n = 74), recurrent disease (n = 16), refusal to attend clinic due to Covid (n = 10). The median age of the cohort was 47.50 yrs (IQR range,30-76yrs), majority of tumours were T2 (69.5%) and node positive disease (46.3%) (Table 1 ). Since the median tumour size was 3 cm, 30% women received neoadjuvant chemotherapy (NACT) followed by BCS. The type of BCS was lumpectomy (80.5%), oncoplasty (14.6%) and revision lumpectomy (4.9%). 69.5% women underwent axillary dissection and the rest SLNB. All patients received boost,42.7% received SCF-RT whereas axillary RT was given to only 2.4% patients (Table 2 ). Though a large proportion of patients were Her-2 neu positive (44%) only 10% could afford trastuzumab. Table 1 Baseline demographic characteristics of the cohort Parameters N (%) Age (median and IQ range in yrs) 47.50 (30–76) Comorbidity HT/DM 17 (20.7) Right side Left side 37 (45.1) 45 (54.9) Premenopausal Postmenopausal 26 (31.7) 56 (68.3) Quadrant Upper outer Lower outer. Rest 62 (75.6) 12 (14.6) 8 (8.5) T clinical T1 T2 T3 T4 Missing N clinical N0 N1 N2 Missing 2 (2.4) 57 (69.5) 18 (22.0) 3 (3.7) 2 (2.4) 44 (53.7) 25 (30.5) 9 (11) 4 (4.9) Grade : G1/G2/G3 5(6.1)/30(36.6)/47(57.3) Intrinsic subtype Luminal A Luminal B Her2 type TNBC 5 (6) 18(22) 36(44) 23(28) Table 2 Intervention received by the cohort. Parameters N (%) NACT (Yes) NACT (No) Trastuzumab 25 (30.5) 57 (69.5) 8 (9.8%) Surgery of primary Lumpectomy Onco-plasty Revision lumpectomy 66 (80.5) 12(14.6) 4 (4.9) Axillary surgery Axillary dissection SLNB 57 (69.5) 25 (30.5) Vol. of excision 100cc 41 (50) 41 (50) Hormone therapy Tamoxifen/Letrozole No hormone 13 (15.9%) /23 (28.0%) 46 (56.1%) Axillary RT given Axillary RT not given SCF RT given SCF RT not given 2 (2.4) 80 (97.6) 35 (42.7) 47 (57.3) PTV boost vol (IQR 77cc-163cc) 100 cc 29 (36.7) 53 (65.3) Breast Volume (IQR 1300cc-2000cc) Medium (includes small) [ 1600cc] 42 (51.2) 40 (48.8) Volume of breast receiving 100% dose (IQR 83cc-213cc) 120 cc 43 (52.4%) 39 (47.6%) Volume of breast receiving 107% dose (IQR 0cc-16cc) 10 cc 67 (81.7) 15 (18.3) The median volume of excision was 100 cc (IQR 60cc-141cc), median planning target volume of boost (PTV) was 100 cc (IQR 77cc-163cc), median breast volume was 1600 cc (IQR 1300cc-2000cc), median breast volume receiving 100% dose was 120 cc (IQR 83cc-213cc), median breast volume receiving 107% dose was 10cc (IQR 0cc-16cc). 2 categories were created in all the above variables for correlation with CE and LE: ( than 100cc for excision volume and PTV boost), ( than 1800cc for breast volume as no meaningful correlation was found with the median value of 1600 cc), ( than 120cc for breast volume receiving 100% RT dose) and ( than 10cc for 107% dose volume). Women with breast volume 1800 cc as large size. Factors predicting cosmesis At a median follow-up of 60 months, the global cosmetic score of the entire cohort was poor in 56% patients. The other ascertained parameters of CA, LE and PROM are listed in Table 3 . On univariate analysis, as compared to women with good cosmesis, women with adverse global cosmesis had significantly higher resected volume (> 100cc in 67% vs 27%, p-value = 0.000), higher dose heterogeneity (> 10cc in 28% vs 2.8%, p-value = 0.009), large breast volume (70% vs 30%, p = 0.08), higher breast volume receiving 100% RT dose (64% vs 36%, p = 0.08), likelihood of receiving NACT (81% vs 19%, p-value = 0.003) and SCF RT (66% vs 34%, p = 0.09) (Table 4 ,Fig. 2 , Fig. 1 s and 2 s). On multivariate analysis of factors affecting various domains of cosmesis and global cosmesis, menopausal status (HR 3.4 ) , volume of resection (HR 3.8) and volume of breast receiving 107% dose (HR 11) had a significant impact on breast size. Receipt of NACT (HR 8.9) and volume of breast receiving 107% (HR 17.9) had a significant impact on breast shape. Volume of breast receiving 107% (HR 17) had a significant impact on nipple position. Receipt of NACT (HR 4.4) and volume of breast receiving 107% (HR 3.8) had a significant impact on scar appearance. Volume of resection (HR 4.6) and receipt of NACT (HR 4.4) had a significant impact on global cosmetic outcome (Table 5 ). Table 3 Incidence of cosmesis and late-effects as assessed by Patient and Physician Patient assessed variables (BR23) Present n (%) Physician assessed variables Grade1,2 n (%) Grade3,4 n (%) Breast pain 29 (35) Breast Size 50 (60) 33 (40) Breast edema 09 (11) Breast shape 57 (70) 25 (30) Breast sensitivity 12 (15) Nipple position 66 (80) 16 (20) Skin of breast 52 (64) Shape of nipple and areola 66 (80) 16 (20) Altered Body image 56 (69) Skin on breast 66 (80) 16 (20) Interested in sex 38 (46) Scar appearance 50 (60) 33 (40) Sexually active 39 (47) Global cosmetic score 36 (44) 46 (56) Sex enjoyable 37 (45) Skin of breast and shoulder 10 (12%) - Arm edema 12 (15%) Arm edema 6 (7.4%) - Shoulder stiffness 16 (20%) Brachial plexopathy 8 (10%) - Pain shoulder 29 (35%) Shoulder stiffness 16 (20%) - Table 4 Univariate analysis of variables affecting cosmesis Variables Good cosmesis % (n) Poor cosmesis % (n) p-value T1,2 (n = 61) T3,4 (n = 21) 49 (30) 28 (6) 51 (31) 72 (15) 0.09 Resected volume 1 00cc (n = 41) 73 (26) 27 (10) 33 (15) 67 (31) 0.000 Type of Breast Surgery Lumpectomy (n = 66) Oncoplasty (n = 12) Revision surgery (n = 4) 27 (40.9) 9 (75) - 39 (59.1) 3 (25) 4 (100) 0.01 NACT (yes) n = 25 NACT (no) n = 57 19 (5) 54 (31) 81 (20) 46 (26) 0.003 Breast Volume Medium (n = 48) Large (n = 34) 71 (25) 30 (10) 53 (23) 70 (24) 0.08 Breast volume receiving 107% dose 10cc, n = 15 34 2.8 (2) 33 (72) 28 (13) 0.009 Br. volume receiving 100% dose 120cc (n = 39) 49 (21) 36(14) 51(22) 64(25) 0.08 SCF RT (yes) (n = 35) SCF RT (No) (n = 47) 66 (24) 34 (12) 50(23) 50(23) 0.09 Table 5 Logistic regression of significant/near significant variables affecting sub-domains of cosmesis and global cosmesis Variables Breast size p-value, HR(CI) Breast shape p-value, HR(CI) Skin breast p-value, HR(CI) Nipple position p-value, HR(CI) Scar appearance p-value, HR(CI) Global cosmetic score p-value, HR(CI) Premenopausal (R) n = 26 Post-meno, n = 56 0 .08(3.4) (0.8–14) 0.3(2) (0.4–10) 0.9(0) (0) 0.1(10) (0.5–180) 0.3(1.4) (0.4-5) 0.3(0.5) (0.4–1.5) Node negative (R), n = 44 Node positive, n = 38 0.8(1.4) (0.1–4.9) 0.5(0.5) (0.05–4.8) 1(0.1) (0) 0.2(4.6) (0.01–3.8) 0.3(0.5) (0.1-2) 0.06(0.3) (0.09–1.1) Resection vol 1 00cc, n = 41 0.06(3.8) (0.9–16) 0.3(2) (0.4–10) 1(0.1) (0) 0.4(3) (0.2–55) 0.4(1.3) (0.2-5) 0.005(4.6) (1.6–13.6) NACT (yes) n = 25 NACT (no, R), n = 57 0.3(2) (0.4–10) 0.006(8.2) (1.8–36.6) 0.9(0) (0) 0.3(3) (0.2–41) 0.009(4.4) (1.4–13) 0.009(6.5) (1.6–26) Br. volume 107% dose 10cc, n = 15 0.004(11) (2–56) 0.001(18) (3-100) 0.19(6.7) (0.38–118) 0.003(17) (3-109) 0.06(3.8) (0.9–16) 0.1(5) (0.5–48) Br. volume 100% dose 120cc, n = 39 0.9(1.1) (0.09-12) 0.8(0.7) (0.06–9.3) 1(0) (0) 0.9(0) (0) 0.6(0.3) (0-4.3) 0.6(5) (0-4-9) SCF RT (yes)n = 35 SCF RT (No, R), n = 47 0.06(0.28) (0.07-1) 0.4(0.5) (0.09–2.9) 0.9(0) (0) 0.1(0.1) (0.01-.15) 0.1(0.4) (0.1–1.3) 0.5(0.7) (0.1–1.3) Factors predicting late-effects in arm and shoulder: Assessment of LE by physician revealed skin changes in breast and shoulder in 12% patients, brachial plexopathy in 4%, shoulder stiffness in 20% and arm oedema in 6% while according to PROM shoulder and arm pain was found in 35%, shoulder stiffness in 20% and arm oedema in15%. On multivariate analysis of factors affecting physician assessed LE in arm and shoulder, tumour size had a trend toward significance (HR 9) for arm oedema, volume of breast receiving 107% had a significant impact on brachial plexopathy (HR 6.1) and shoulder stiffness (HR 4). Presence of comorbidity also affected shoulder stiffness (HR 3.9) (Table 6 ). Table 6 Logistic regression of significant /near significant variables affecting late-effects in arm and shoulder. Variables Arm edema P-value,HR(CI) Brachial plexopathy p-value,HR(CI) Shoulder stiffness, P-value,HR(CI) Skin arm, shoulder p-value,HR(CI) Comorbidity (no,R) (n = 65) Comorbidity (yes) (n = 17) 0.3(0.2) (0.02-1) 0.06(0.2) (0.04-1) 0.07 (4.8) (0.6–8.7) 0.13(3) (0.7–13) T 3cm, (n = 23) 0.09(7.2) (0.6–76 ) 0.2(0.3) (0.4–3.7) 0.6 (1.3) (0.3–5.7) 0.4(2.2) (0.3–16) Volume receiving 107% 10cc (n = 15) 0.9 (0) (0) 0.03(6.1) (1.1–33.5) 0 .07(4) (0.8–18) 0.2 (2.8) (0.4–18) Factors predicting PROM Patients reported breast pain in 35%, breast oedema in 11%, breast sensitivity in 15%, change in skin of breast in 64%. Sexual parameters like sexual interest was present in 46%, 47% were sexually active and sex was enjoyable in 45%. The log transformed systemic symptom score was poor in 34% women, arm score was poor in 33%, breast score was poor in 27%, and hair loss was bothersome for 75% women. Body image perception was poor in 69% women, sexual function and enjoyment was poor in 30% and 25% women and 80% of them were bothered about their future. On multivariate analysis of factors affecting symptom and functional scales, postmenopausal status was associated with higher arm score, breast score, hair loss, and sexual function decline. Node positive status was also associated with higher arm score. High breast volume and premenopausal status had a trend towards higher breast score. T size more than 3 cm and receipt of SCF RT shows significantly higher altered body image (Table 7 ,8 Fig. 3 s). Table 7 Logistic regression of significant/near significant variables affecting PROM. Symptom scale (p value, (HR)) Functional scale (p value, (HR)) Variables Systemic score 21 ± 14.6 (0–85) Arm score 15 ± 21 (0–77) Breast score 15 ± 12 (0–66) Hair loss 31 ± 24 (0-100) Body image 80 ± 22 (16–100) Sexual function 75 ± 27 Sexual enjoyment Future 66 ± 22 (0-100) Premenopausal (R) (n = 26) Postmenopausal, (n = 56) 0.1(6.2) 0.03 (4.9) 0.03 (7.3) 0.03 (7.3) 0.5(1.6) 0.02(5.8) 0.02(5.8) 0.5(1.7) T 3cm, (n = 23) 0.5(1.6) 0.18(0.13) 0.5(0.29) 0.5 (0.2) 0.07 (3.2) 0.3(2.5) 0.5(2.5) 0.3(0.3) Node negative (R), (n = 44) Node positive, (n = 38) 0.5(1.8) 0.07 (4.3) 0.35 (2.8) 0.3 (2.2) 0.8(1.2) 0.1(0.2) 0.1(0.2) 0.7(1.3) Breast Volume Medium (R), (n = 42) Large, (n = 40) .09 (3.6) 0.7(0.7) .07 (5.4) 0.07 (7.4) 0.4(0.5) 0.7(1.3) 0.7(1.3) 0.8(0.8) SCF RT (yes) (n = 35) SCF RT (No) (n = 47) 0.9 (0.9) 0.09(0.2) 0.13 (0.17) 0.2(1.8) 0.02(0.1) 0.9(1) 0.9 (1) 0.1(0.3) Discussion One of the important endpoints of successful implementation of breast conservation is cosmesis. The standard of care for cosmesis assessment is clinical assessment, which we were able to conduct in 82 patients during the period November 2020 to September 2021.Since we investigated women with a median follow-up of 5 years, a cross-sectional study is adequate, as any further change in cosmesis is usually not observed after 3 years of RT completion. After invitation with several rounds of phone calls only 46% patients participated in this study and the rest could not be contacted due to change in phone number or non-receipt of calls (40%), due to death (9%), and the reluctance to visit OPD due to Covid. Clinicians are able to assess the breast with a 3-D view whereas this is not possible with standard photographs. Varying thresholds of experience in grading toxicity between clinicians can lead to interobserver variability which we did not face because both the clinicians conducted the CA of the same patient together. We did not indulge in complex methods of cosmetic assessment like BCTOS or use of BCCT software because these cannot be used in the clinic daily even though they are more accurate. Most of the reported cosmesis studies of hypofractionation are in patients with early-stage tumours while our study comprised of patients with high-risk features like T2 or more [95%], node positive [50%], chemotherapy [97%] and SCF RT [43%]. In START B, 70% patients were T1, 72% were node negative and any change in breast appearance (mild or marked) at 5 years recorded using the consensus scores was seen in only 39.3%. The incidence of poor cosmesis by physician assessment was 38% with hypofractionation as compared to 44% with conventional fractionation [ 7 ]. This incidence of poor cosmesis by physician assessment increased to 43% with hypo-fractionated boost as compared to 50% with conventional fractionation boost. In our series all patients received boost and with the presence of high-risk features the incidence of adverse cosmesis was 56%. Similar observations of poor cosmesis have been observed with hypo-fractionated RT in women with high-risk features in 61% [ 8 ]. Administration of CT has been reported to be associated with worse cosmesis [ 9 ]. The EORTC study reported significant association of the risk of moderate to severe fibrosis with administration of CT and or tamoxifen in premenopausal or postmenopausal women respectively. The DBCG group observed excellent to good cosmesis in only 50% patients in a population of patients with predominantly T1 tumours (80%) treated with conventional fractionation, where apart from physician assessment, nipple position was also ascertained with BCCT.core software [ 10 ]. Conventional fractionation has been found to result in poor cosmesis as compared to hypofractionation [ 11 ]. Apart from high-risk features, the surgical factors contributing to high incidence of adverse cosmesis in our patients was large resection volumes (> 100cc) in approximately 50% patients which is a reflection of 37% tumours being more than 3 cm. In a study of CA in 598 early breast cancer, the resection of 70 cc or more of breast tissue was more common among the failed patients than among matched patients with good or excellent cosmesis [ 12 ]. For safe and cosmetically acceptable breast-conserving therapy in patients with large breast cancers, the tumour volume should be reduced preoperatively by NACT, and lost tissue volume should be replaced after wide local excision by oncoplastic techniques. During the period of assessment in the index study, only 12 patients with oncoplastic technique turned up for CA and the cosmetic outcome of these patients was good in 75% patients as compared to good cosmesis in 44% patients who underwent non-oncoplasty surgery. As more oncoplastic techniques are gradually being adopted by our surgeons, the cosmesis rate is likely to improve in near future. The radiotherapy related factors which contributed to poor cosmesis were large breast volume, volume of breast receiving 107% or more dose, and volume of breast receiving 100% / 95% dose. In our series we estimated the surrogate of breast volume (from treatment planning scan) ie the volume encompassed by 50% isodose as mentioned in IMPORT Low [ 13 ]. They reported a median volume of 778 cc, 1114 cc and 1357 cc as cut-off volumes for small, medium and large breast when corelated with cup size. Since our series was a retrospective analysis and we did not have the previous bra cup size of our patients to correlate with breast volumes, we sought to correlate with published data. In our series we adopted the cut-off value of 1800 cc (instead of mean value of 1600cc with which no correlation was found) and got a correlation of adverse cosmesis with increase in breast volume beyond 1800cc. Yarnold et al reported a hazard ratio of 1.8 for poor cosmesis in patients receiving 100% dose to more than 42% volume of breast while we found a HR of 12 [ 14 ]. Similar findings have been reported by Mukesh et al., who found improved dose homogeneity with simple IMRT which translated into superior overall cosmesis and reduction in the risk of skin telangiectasia [ 15 ]. Surprisingly boost PTV volume (> 100cc) did not significantly affect cosmesis in our series as reported by Young Boost trial, where the cosmesis was poor if the boost dose was more than 16 Gy, boost volume was high and photon boost was given [ 16 ]. Nodal positivity mandates RT to SCF with or without axillary RT depending on the risk factors. We observed higher incidence of adverse cosmesis in women who received RT to SCF (HR 0.7). Similar findings have been reported in a study where 89% of patients treated with a tangent pair technique had excellent results at 5 years when treated with tangential beams alone as compared with 69% of patients treated with tangents and SCF RT [ 10 ]. SCF RT has also been found to contribute to poor cosmesis in some studies with hypofractionation [ 17 ]. The other factors which resulted in poor cosmesis were postmenopausal status (60%), upper outer quadrant tumours. Though the literature suggests adverse cosmesis in inner quadrant and central tumours, our series had low numbers of other quadrant tumours (only 25%) [ 16 ]. Amongst the various domains which contributed to global cosmesis, the most significant factors affecting global cosmesis were breast size, shape and nipple position. Breast size is a surrogate of resection volume and hence alteration of this domain is expected to impact global cosmesis, which is what we observed in our series also. Secondly high resection volume will also alter the shape and nipple position so these subdomains also impacted global cosmesis in our series. Regarding late-effects, tumour size more than 3 cm was a significant factor contributing to arm oedema (6%). Sentinel LN procedure led to lower (4.3%) incidence of arm oedema as compared to 9% with axillary clearance. Factors significantly impacting brachial plexopathy and shoulder stiffness were presence of comorbidity and volume of breast receiving 107% dose. The START trial reported an incidence of 8% arm edema, 18% shoulder stiffness with hypofractionation as compared to 6% and 8% with conventional fractionation. The Danish study of early BC treated with conventional fractionation reported that the number of positive axillary nodes > 10 and axillary RT increased the arm oedema rate from 7–28%, arm pain from 13–28%, shoulder stiffness from 0 to 8% [ 18 ]. Their 10year follow-up study stated that 64% patients had one or more subjective loco regional symptoms like pain, swelling of the arm, and decreased shoulder mobility. In our series higher LE in arm and shoulder was observed in those who received SCF RT (26% shoulder stiffness versus 18%) which is comparable to the literature. Patient reported Outcome measures: As an increasing number of successfully treated patients have to deal with the results of local treatment on a daily basis, self-reported cosmetic outcome and satisfaction have become critical endpoints of BCT. Since the BR23 questionaire does not capture data pertaining to cosmesis, a direct ascertainment of patient reported cosmesis is not possible, but an indirect assessment was done from breast score and body image. Though the breast score was poor in 26% women in the index study, their perception of the body image was poor in 69%. There is enough data which states that women who were dissatisfied with their cosmetic results had an impaired body image. Data from START reported 20% incidence of patient reported poor cosmesis with 2 field hypo-fractionated breast RT in early BC. Breast pain can result from injury to muscle and ligaments and is more likely to be transient as compared to persistent neuropathic pain due to damage to the nerve tissue. This affects QOL in survivors and was present in 33% women in the index study. Similarly 40% women had marked symptoms in arm and shoulder and one third had breast symptoms, while incidence of same was 20% and 33% in START trials [ 7 , 19 ]. In the index study, arm score had correlation with positive nodal status (HR 4.3), and breast score with breast volume (> 1600cc) (HR 5.4) and premenopausal status (HR 7.3) which has been reported in literature also [ 11 ]. Sexual dysfunction is common in breast cancer survivors and has been found to be associated with feeling of emotional separation in couples, fear of sexual intercourse, lower emotional functioning, poorer body image or co-morbidities [ 20 , 21 ]. In our series only 70% women were sexually active or found it enjoyable, and this was more adversely affected in premenopausal women. The START and IMPORT trial results reveal that PROMs could potentially replace either CA or photographs to assess cosmesis since patients rate their subjective satisfaction with an experience of a range of breast changes, whilst clinicians seek objective adverse treatment effects. Since CA are still widely used all over the globe, an alternative viewpoint is that both PROMs and CAs are necessary as they measure differing aspects of disease experience and are complementary. LIMITATIONS The main limitation of our study was only 46% attendance of BCS patients for cosmesis evaluation because of various reasons mentioned earlier. The other limitation of our study was that the BR 23 questionaire does not directly evaluate PR cosmesis, rather variables assessing change in skin appearance, firmness in the area of the affected breast, asymmetry and distortion and shrinkage of breast as used for START trial would have captured adequate information for PR cosmesis. CONCLUSIONS The presence of high-risk features in 50% women in our population resulted in higher incidence of adverse global cosmesis, LE and PROMs. Declarations The authors declare that no funds, grants, or other support were received during the preparation of this manuscript. The authors affirm that human research participants provided informed consent for publication of the images in Figure 1. All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by [Chandrashekhar Mishra], [Sushma Agrawal]. The first draft of the manuscript was written by [Sushma Agrawal] and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript. Data availability: The datasets generated during and/or analysed during the current study are not publicly available due to Institute policy but are available from the corresponding author on reasonable request. Ethics approval: This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Institute Ethics Committee of University B (Date 2.9.20./No2018-82-IP-EXP). Consent to participate : “Informed consent was obtained from all individual participants included in the study.” Competing interests: The authors declare that they have no competing interests. Non-funded study. Author Contribution CM: collected patient data wrote the manuscriptSA: treated patients, contributed to data, and analysed data and wrote the manuscriptPL: treated patients and contributed to data.GC: treated patients and contributed to data.GA: treated patients and contributed to data. References Whelan T, MacKenzie R, Julian J, Levine M, Shelley W, Grimard L, et al. Randomized trial of breast irradiation schedules after lumpectomy for women with lymph node‑negative breast cancer. J Natl Cancer Inst 2002; 94:1143‑50. DOI: 10.1093/jnci/94.15.1143 START Trialists’ Group, Bentzen SM, Agrawal RK, Aird EG, Barrett JM, Barrett‑Lee PJ, et al. The UK standardisation of breast radiotherapy (START) trial B of radiotherapy hypofractionation for treatment of early breast cancer: A randomised trial. Lancet 2008; 371:1098‑107. doi: 10.1016/S0140-6736(08) 60348-7. Smith BD, Bellon JR, Blitzblau R, Freedman G, Haffty B, Hahn C, Halberg F, Hoffman K, Horst K, Moran J, Patton C, Perlmutter J, Warren L, Whelan T, Wright JL, Jagsi R. Radiation therapy for the whole breast: Executive summary of an American Society for Radiation Oncology (ASTRO) evidence-based guideline. Pract Radiat Oncol. 2018 8(3):145-152. DOI: 10.1016/j.prro.2018.01.012 Krug D, Baumann R, Combs SE, Duma MN et al. Moderate hypofractionation remains the standard of care for whole-breast radiotherapy in breast cancer: Considerations regarding FAST and FAST-Forward. Strahlenther Onkol. 2021;197(4):269-280. DOI: 10.1007/s00066-020-01744-3 Rajan Yadav, Punita Lal, Sushma Agarwal, Shagun Misra, Mranalini Verma, K. J. Maria Das, S. K. Senthil Kumar, Anup Kumar, S. K. Mishra, Amit Agarwal, Gaurav Agarwal, Anjali Mishra, Gyan Chand, AK. Verma, Shaleen Kumar. Comparative retrospective analysis of locoregional recurrence in unselected breast cancer patients treated with conventional versus hypo-fractionated radiotherapy at a tertiary cancer center? Journal of Cancer Research and Therapeutics. 2020.16(6):1314-1322. DOI: 10.4103/jcrt.JCRT_389_18 Agarwal G, Ramakant P.Breast Cancer Care in India: The Current Scenario and the Challenges for the Future. Breast Care (Basel).2008 3(1):21-27. doi:10.1159/000115288 Haviland JS, Hopwood P, Mills J, Sydenham M et al. Do patient reported outcome measures agree with clinical and photographic assessments of normal tissue effects after breast radiotherapy? The experience of the standardisation of breast radiotherapy (START) trials in early breast cancer. Clin Oncol 2016.;28:345–53. doi:10.1016/j.clon.2016.01.011. Tabassum Wadasadawala, Shwetabh Sinha, Vani Parmar et al. Comparison of subjective, objective and patient‑reported cosmetic outcomes between accelerated partial breast irradiation and whole breast radiotherapy: a prospective propensity score‑matched pair Analysis. Breast Cancer, 2020; 27 :206–212. doi.org/10.1007/s12282-019-01009-7. Budrukkar AN, Sarin R, Shrivastava SK, Deshpande DD, Dinshaw. Cosmesis, late sequelae and local control after breast-conserving therapy: influence of type of tumour bed boost and adjuvant chemotherapy. Clin Oncol (R Coll Radiol) . 2007;19(8):596-603.DOI: 10.1016/j.clon.2007.06.008 Christina D Lyngholm , Peer M Christiansen, Tine E Damsgaard, Jens Overgaard. Long-term follow-up of late morbidity, cosmetic outcome and body image after breast conserving therapy. A study from the Danish Breast Cancer Cooperative Group (DBCG). Acta Oncol 2013;52(2):259-69. DOI: 10.3109/0284186X.2012.744469 . Reshma Jagsi, MD, Kent A. Griffith, Frank Vicini, et al. Toward Improving Patients’ Experiences of Acute Toxicity From Breast Radiotherapy: Insights From the Analysis of Patient-Reported Outcomes in a Large Multicenter Cohort. J Clin Oncol 2020; 38:4019-4029. Olivotto IA, Rose MA, Osteen RT, et al. Late cosmetic outcome after conservative surgery and radiotherapy: analysis of causes of cosmetic failure. Int J Radiat Oncol Biol Phys. 1989;17:747e753. DOI: 10.1016/0360-3016(89)90061-8 Bhattacharya IS, Haviland JS, Hopwood P et al. Can patient-reported outcomes be used instead of clinician-reported outcomes and photographs as primary endpoints of late normal tissue effects in breast radiotherapy trials? Results from the IMPORT LOW trial. Radiother Oncol. 2019 134:220-230. doi: 10.1016/j.radonc.2019.01.036. Christy Goldsmith, Joanne Haviland, Yat Tsang et al. Large breast size as a risk factor for late adverse effects of breast radiotherapy: Is residual dose inhomogeneity, despite 3D treatment planning and delivery, the main explanation? Radiotherapy and Oncology 100:236-240 doi:10.1016/j.radonc.2010.12.012 Mukesh MB, Qian W, Wah Hak CC, Wilkinson JS, Barnett GC, Moody AM, et al. Breast Intensity-modulated Radiotherapy Trial: Comparison of Clinician versus Patient-reported Outcomes. Clin Oncol (Royal College of Radiologists (Great Britain)) 2016;28:354–64.DOI: 10.1016/j.clon.2016.02.011 Brouwers PJAM, van Werkhoven E, Bartelink H et al. Predictors for poor cosmetic outcome in patients with early stage breast cancer treated with breast conserving therapy: Results of the Young boost trial. Radiother Oncol.2018;128(3):434441. doi:10.1016/j.radonc.2018.06.020. Di Wang, Xiaofeng Yang, Jiabei He et al. The Impact of Regional Nodal Irradiation and Hypo-fractionated Whole Breast Radiation on Long Term Breast Retraction and Poor Cosmetic Outcome in Breast Cancer Survivors. Clinical Breast Cancer. 2020; 2020 Feb;20(1):e75-e81 David Peterson , Pauline T Truong , Sameer Parpia , Ivo A Olivotto. Predictors of adverse cosmetic outcome in the RAPID trial: an exploratory analysis , Int J Radiat Oncol Biol Phys . 2015;91(5):968-76. DOI: 10.1016/j.ijrobp.2014.12.040 Katrine Rye Hauerslevhttps, Anders Husted Madsenb, Jens Overgaard, Tine Engberg Damsgaarda, and Peer Christiansen. Long-term follow-up on shoulder and arm morbidity in patients treated for early breast cancer. Acta Oncologica 2020; 59 (7):851-858.DOI: White J, Joiner MC. Toxicity from radiation in breast cancer. Cancer Treat Res 2006; 128:65-109. DOI:10.1007/0-387-25354-8_5 Anne Bredart S Dolbeault, A Savignoni etal. Prevalence and associated factors of sexual problems after early-stage breast cancer treatment: results of a French exploratory survey. Psycho-oncology 2011:20(8):841-50. doi: 10.1002/pon.1789. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-3836655","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":265525950,"identity":"8d22809c-7f92-41cc-9b31-fa4352e3daba","order_by":0,"name":"Chandrashekhar Mishra#","email":"","orcid":"","institution":"Sanjay Gandhi Post Graduate Institute of Medical Sciences","correspondingAuthor":false,"prefix":"","firstName":"Chandrashekhar","middleName":"","lastName":"Mishra#","suffix":""},{"id":265525951,"identity":"76cd7122-b072-4feb-a4c0-6685ba10c317","order_by":1,"name":"Sushma Agrawal#","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABAUlEQVRIiWNgGAWjYHACNgTzQQUDgwGMI0GUloQzJGtJbCNCi/yM9GePbtTY2W1vP2P4IXHeYXlz9uYDDD8qGBJnNmDXYnAjx9w451hy8pwzOcYSidsOG+7sOZbA2HOGIXE2DlsMJHLYpHPYmJMlGHI3gLQwbriRY8DM2MaQOA+Pw6Rz/tUnS/C/3fwjcc5he4JaGG4kmEnnth22k5DI3SaR2HA4Ea4Fp8POvAFq6TueICHx/ptFwrH05A1njiUc7DkjYYzL+/LtIId9q7aX4E9LvvGhxtp2w/Hmgw9+VNjIzjiAy2UQkAg1shlMHsAbkVBgD6XrCKocBaNgFIyCkQcAIZpfdL1oDugAAAAASUVORK5CYII=","orcid":"","institution":"Sanjay Gandhi Post Graduate Institute of Medical Sciences","correspondingAuthor":true,"prefix":"","firstName":"Sushma","middleName":"","lastName":"Agrawal#","suffix":""},{"id":265525952,"identity":"279c990e-031d-40fc-88dd-1184b642b75e","order_by":2,"name":"Punita Lal#","email":"","orcid":"","institution":"Sanjay Gandhi Post Graduate Institute of Medical Sciences","correspondingAuthor":false,"prefix":"","firstName":"Punita","middleName":"","lastName":"Lal#","suffix":""},{"id":265525953,"identity":"910f1a75-cfbf-4015-aec8-a59eba9f8b25","order_by":3,"name":"Gyan Chand","email":"","orcid":"","institution":"Sanjay Gandhi Post Graduate Institute of Medical Sciences","correspondingAuthor":false,"prefix":"","firstName":"Gyan","middleName":"","lastName":"Chand","suffix":""},{"id":265525954,"identity":"15633d23-f226-4de7-971f-373152d0e58a","order_by":4,"name":"Gaurav Agarwal","email":"","orcid":"","institution":"Sanjay Gandhi Post Graduate Institute of Medical Sciences","correspondingAuthor":false,"prefix":"","firstName":"Gaurav","middleName":"","lastName":"Agarwal","suffix":""}],"badges":[],"createdAt":"2024-01-05 08:14:13","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-3836655/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-3836655/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":49333758,"identity":"f662a35e-7186-47fe-acf2-cee6d1c5c68e","added_by":"auto","created_at":"2024-01-08 20:00:42","extension":"jpeg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":382036,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eAn example of patient with poor cosmesis and marked skin changes.\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"floatimage1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-3836655/v1/c1302130964460b32a13dc26.jpeg"},{"id":49333467,"identity":"56eecdad-b4ca-4ed7-998e-7bc7dcb83316","added_by":"auto","created_at":"2024-01-08 19:52:42","extension":"jpeg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":175102,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eImpact of type of surgery on Global cosmesis\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"floatimage3.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-3836655/v1/712abc55669657ed0038ff90.jpeg"},{"id":49333465,"identity":"d795352f-c716-456a-b8be-2147a1584603","added_by":"auto","created_at":"2024-01-08 19:52:42","extension":"jpeg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":183735,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003ePatient reported outcome scores (BR23).\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"floatimage5.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-3836655/v1/02b735fb6badd7d011ebff79.jpeg"},{"id":49389150,"identity":"439fc5aa-638e-47f2-9850-378e605f0d87","added_by":"auto","created_at":"2024-01-09 21:52:18","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1154407,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3836655/v1/413a9a95-c10d-4372-8333-0bd6c4e96a26.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Factors predicting Cosmesis (CA), Late effects (LE) and Patient reported outcome measures (PROM) in high-risk breast cancer (BC) treated with hypo-fractionated radiotherapy (HF-WBI): real world outcomes from a developing country","fulltext":[{"header":"Introduction","content":"\u003cp\u003eBCS is the standard of care in early breast cancer and LO disease adequately down-staged with chemotherapy (CT) which is followed by whole breast radiotherapy and boost to the resection cavity. Results from large randomized trials have confirmed that hypo-fractionated whole-breast irradiation (HF-WBI) is safe and efficacious in comparison to conventional fractionation in early-stage breast cancer [1,2]. Moreover, the recent update of the American Society of Radiation Oncology (ASTRO) evidence-based guidelines on radiation therapy for the whole breast confirmed that HF-WBI represents the preferred option for patients with early-stage breast cancer, regardless of age, chemotherapy administration and breast size and recommends minimization of breast volume receiving \u0026gt;105% of the prescription dose [3]. Real world data have confirmed the safety and efficacy of hypo-fractionated RT in early BC and LABC in various studies [4,5]. Cosmesis is an important endpoint of successful implementation of breast conservation. While the reported cosmesis with HF-WBI is good in early BC, there is sparse literature on the cosmesis and late-effects in with LO/LABC.\u003c/p\u003e\n\u003cp\u003eIn our country, women more often present with LO/LABC [6]. Though we have reported the safety and efficacy of HF-WBI in LO/LABC, cosmetic outcome and late-effects analysis had not yet been conducted [5]. Hence we conducted a cross-sectional study of women who underwent BCS during a 5 year period with at least 3 years follow-up, to ascertain the CA and LE in arm and shoulder and PROM.\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cp\u003eAfter approval of institute ethics committee (2018-82-IP-EXP), all patients of BC who underwent BCS during the period 2013 to 2017 and who could attend the clinic for cosmesis and LE assessment for arm and shoulder were enrolled in this study. Women underwent upfront BCS in those who were suitable, while large operable and locally advanced tumours underwent BCS after adequate downstaging with standard neoadjuvant chemotherapy. All were treated with HF-WBI whole breast RT and supraclavicular RT (in node positive) by 3DCRT technique to a dose of 40 Gy/15 fractions in 3 weeks followed by boost (10 Gy/4\u0026ndash;5 fractions) to tumour bed. IMRT (field in field technique) was used when necessary to improve homogeneity of target volume coverage. All hormone receptor positive patients received either tamoxifen or letrozole according to their menopausal status and trastuzumab was administered to Her-2 neu positive women.\u003c/p\u003e\n\u003cp\u003eTwo physicians (SA and CM) together assessed cosmesis (CA) and LE using the EORTC and RTOG scoring system respectively. Patient reported outcome measures (PROM) was collected with EORTC-BR23 questionnaire.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData and statistical analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe \u0026lsquo;\u0026lsquo;quite a bit\u0026rdquo; and \u0026lsquo;\u0026lsquo;very much\u0026rdquo; categories of all endpoints of CA, LE and PROM were combined into one category (moderate/marked), similarly none and a little were combined into another category (mild) which resulted in a 2-point scale. Logistic regression\u0026nbsp;was used to assess the effect of all the tumour and treatment variables on the risk of cosmesis, late-effects and PROMs. Each factor was first tested alone in a univariate model, and then significant factors were tested in a multivariate analysis to test whether the effects were independent of each other. A value of p\u0026thinsp;=\u0026thinsp;0.05 was taken as significant. Analysis of PROM using BR23 was used as stated in the questionnaire. The raw scores obtained from the questionnaire were linearly transformed to a 0\u0026ndash;100 range.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eOut of 186 patients who underwent BCS followed by HF-WBI (2013-17), only 86 patients could attend OPD for cosmesis and LE assessment due to Covid. Four among these underwent APBI (accelerated partial breast radiation) so they were excluded from the analysis to ensure data of a homogenously treated population. The cause of non-enrollment of 100 patients in this study were: change in contact number (n\u0026thinsp;=\u0026thinsp;74), recurrent disease (n\u0026thinsp;=\u0026thinsp;16), refusal to attend clinic due to Covid (n\u0026thinsp;=\u0026thinsp;10). The median age of the cohort was 47.50 yrs (IQR range,30-76yrs), majority of tumours were T2 (69.5%) and node positive disease (46.3%) (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e). Since the median tumour size was 3 cm, 30% women received neoadjuvant chemotherapy (NACT) followed by BCS. The type of BCS was lumpectomy (80.5%), oncoplasty (14.6%) and revision lumpectomy (4.9%). 69.5% women underwent axillary dissection and the rest SLNB. All patients received boost,42.7% received SCF-RT whereas axillary RT was given to only 2.4% patients (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e). Though a large proportion of patients were Her-2 neu positive (44%) only 10% could afford trastuzumab.\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003ctable id=\"Tab1\" border=\"1\"\u003e\u003ccaption\u003e\n\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\n\u003cdiv class=\"CaptionContent\"\u003e\n\u003cp\u003eBaseline demographic characteristics of the cohort\u003c/p\u003e\n\u003c/div\u003e\n\u003c/caption\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eParameters\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eN (%)\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003c/thead\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eAge\u003c/strong\u003e (median and IQ range in yrs)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e47.50 (30\u0026ndash;76)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eComorbidity\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eHT/DM\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e17 (20.7)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eRight side\u003c/p\u003e\n\u003cp\u003eLeft side\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e37 (45.1)\u003c/p\u003e\n\u003cp\u003e45 (54.9)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ePremenopausal\u003c/p\u003e\n\u003cp\u003ePostmenopausal\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e26 (31.7)\u003c/p\u003e\n\u003cp\u003e56 (68.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eQuadrant\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eUpper outer\u003c/p\u003e\n\u003cp\u003eLower outer.\u003c/p\u003e\n\u003cp\u003eRest\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e62 (75.6)\u003c/p\u003e\n\u003cp\u003e12 (14.6)\u003c/p\u003e\n\u003cp\u003e8 (8.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eT clinical\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eT1\u003c/p\u003e\n\u003cp\u003eT2\u003c/p\u003e\n\u003cp\u003eT3\u003c/p\u003e\n\u003cp\u003eT4\u003c/p\u003e\n\u003cp\u003eMissing\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eN clinical\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eN0\u003c/p\u003e\n\u003cp\u003eN1\u003c/p\u003e\n\u003cp\u003eN2\u003c/p\u003e\n\u003cp\u003eMissing\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e2 (2.4)\u003c/p\u003e\n\u003cp\u003e57 (69.5)\u003c/p\u003e\n\u003cp\u003e18 (22.0)\u003c/p\u003e\n\u003cp\u003e3 (3.7)\u003c/p\u003e\n\u003cp\u003e2 (2.4)\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e44 (53.7)\u003c/p\u003e\n\u003cp\u003e25 (30.5)\u003c/p\u003e\n\u003cp\u003e9 (11)\u003c/p\u003e\n\u003cp\u003e4 (4.9)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eGrade\u003c/strong\u003e: G1/G2/G3\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e5(6.1)/30(36.6)/47(57.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eIntrinsic subtype\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eLuminal A\u003c/p\u003e\n\u003cp\u003eLuminal B\u003c/p\u003e\n\u003cp\u003eHer2 type\u003c/p\u003e\n\u003cp\u003eTNBC\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e5 (6)\u003c/p\u003e\n\u003cp\u003e18(22)\u003c/p\u003e\n\u003cp\u003e36(44)\u003c/p\u003e\n\u003cp\u003e23(28)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003c/div\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n\u003ctable id=\"Tab2\" border=\"1\"\u003e\u003ccaption\u003e\n\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\n\u003cdiv class=\"CaptionContent\"\u003e\n\u003cp\u003eIntervention received by the cohort.\u003c/p\u003e\n\u003c/div\u003e\n\u003c/caption\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eParameters\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eN (%)\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eNACT (Yes)\u003c/p\u003e\n\u003cp\u003eNACT (No)\u003c/p\u003e\n\u003cp\u003eTrastuzumab\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003e25 (30.5)\u003c/p\u003e\n\u003cp\u003e57 (69.5)\u003c/p\u003e\n\u003cp\u003e8 (9.8%)\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eSurgery of primary\u003c/p\u003e\n\u003cp\u003eLumpectomy\u003c/p\u003e\n\u003cp\u003eOnco-plasty\u003c/p\u003e\n\u003cp\u003eRevision lumpectomy\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e66 (80.5)\u003c/p\u003e\n\u003cp\u003e12(14.6)\u003c/p\u003e\n\u003cp\u003e4 (4.9)\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003c/thead\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eAxillary surgery\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAxillary dissection\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSLNB\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e57 (69.5)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e25 (30.5)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eVol. of excision\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026lt;\u0026thinsp;100cc\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026gt;\u0026thinsp;100cc\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e41 (50)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e41 (50)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eHormone therapy\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTamoxifen/Letrozole\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eNo hormone\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e13 (15.9%) /23 (28.0%)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e46 (56.1%)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eAxillary RT given\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAxillary RT not given\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSCF RT given\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSCF RT not given\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003e2 (2.4)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e80 (97.6)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e35 (42.7)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e47 (57.3)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003ePTV boost vol (IQR 77cc-163cc)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026lt;\u0026thinsp;100 cc\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026gt;100 cc\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e29 (36.7)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e53 (65.3)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eBreast Volume (IQR 1300cc-2000cc)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMedium (includes small) [\u0026lt;\u0026thinsp;1600cc]\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eLarge (\u0026gt;\u0026thinsp;1600cc]\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e42 (51.2)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e40 (48.8)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eVolume of breast receiving 100% dose (IQR 83cc-213cc)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026lt;\u0026thinsp;120 cc\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026gt;\u0026thinsp;120 cc\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e43 (52.4%)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e39 (47.6%)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eVolume of breast receiving 107% dose (IQR 0cc-16cc)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026lt;\u0026thinsp;10 cc\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026gt;\u0026thinsp;10 cc\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e67 (81.7)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e15 (18.3)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003eThe median volume of excision was 100 cc (IQR 60cc-141cc), median planning target volume of boost (PTV) was 100 cc (IQR 77cc-163cc), median breast volume was 1600 cc (IQR 1300cc-2000cc), median breast volume receiving 100% dose was 120 cc (IQR 83cc-213cc), median breast volume receiving 107% dose was 10cc (IQR 0cc-16cc). 2 categories were created in all the above variables for correlation with CE and LE: (\u0026lt;\u0026thinsp;and \u0026gt;\u0026thinsp;than 100cc for excision volume and PTV boost), (\u0026lt;\u0026thinsp;1800 and \u0026gt;\u0026thinsp;than 1800cc for breast volume as no meaningful correlation was found with the median value of 1600 cc), (\u0026lt;\u0026thinsp;and \u0026gt;\u0026thinsp;than 120cc for breast volume receiving 100% RT dose) and (\u0026lt;\u0026thinsp;and \u0026gt;\u0026thinsp;than 10cc for 107% dose volume). Women with breast volume\u0026thinsp;\u0026lt;\u0026thinsp;1800 cc were considered medium size breast and \u0026gt;\u0026thinsp;1800 cc as large size.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFactors predicting cosmesis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAt a median follow-up of 60 months, the global cosmetic score of the entire cohort was poor in 56% patients. The other ascertained parameters of CA, LE and PROM are listed in Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e. On univariate analysis, as compared to women with good cosmesis, women with adverse global cosmesis had significantly higher resected volume (\u0026gt;\u0026thinsp;100cc in 67% vs 27%, p-value\u0026thinsp;=\u0026thinsp;0.000), higher dose heterogeneity (\u0026gt;\u0026thinsp;10cc in 28% vs 2.8%, p-value\u0026thinsp;=\u0026thinsp;0.009), large breast volume (70% vs 30%, p\u0026thinsp;=\u0026thinsp;0.08), higher breast volume receiving 100% RT dose (64% vs 36%, p\u0026thinsp;=\u0026thinsp;0.08), likelihood of receiving NACT (81% vs 19%, p-value\u0026thinsp;=\u0026thinsp;0.003) and SCF RT (66% vs 34%, p\u0026thinsp;=\u0026thinsp;0.09) (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003e,Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e, Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003es and \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003es). On multivariate analysis of factors affecting various domains of cosmesis and global cosmesis, menopausal status (HR 3.4\u003cstrong\u003e)\u003c/strong\u003e, volume of resection (HR 3.8) and volume of breast receiving 107% dose (HR 11) had a significant impact on breast size. Receipt of NACT (HR 8.9) and volume of breast receiving 107% (HR 17.9) had a significant impact on breast shape. Volume of breast receiving 107% (HR 17) had a significant impact on nipple position. Receipt of NACT (HR 4.4) and volume of breast receiving 107% (HR 3.8) had a significant impact on scar appearance. Volume of resection (HR 4.6) and receipt of NACT (HR 4.4) had a significant impact on global cosmetic outcome (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e5\u003c/span\u003e).\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003ctable id=\"Tab3\" border=\"1\"\u003e\u003ccaption\u003e\n\u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\n\u003cdiv class=\"CaptionContent\"\u003e\n\u003cp\u003eIncidence of cosmesis and late-effects as assessed by Patient and Physician\u003c/p\u003e\n\u003c/div\u003e\n\u003c/caption\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003ePatient assessed variables (BR23)\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003ePresent n (%)\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003ePhysician assessed variables\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eGrade1,2\u003c/p\u003e\n\u003cp\u003en (%)\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eGrade3,4\u003c/p\u003e\n\u003cp\u003en (%)\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003c/thead\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eBreast pain\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e29 (35)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eBreast Size\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e50 (60)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e33 (40)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eBreast edema\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e09 (11)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eBreast shape\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e57 (70)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e25 (30)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eBreast sensitivity\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e12 (15)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNipple position\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e66 (80)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e16 (20)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eSkin of breast\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e52 (64)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eShape of nipple and areola\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e66 (80)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e16 (20)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eAltered Body image\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e56 (69)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eSkin on breast\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e66 (80)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e16 (20)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eInterested in sex\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e38 (46)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eScar appearance\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e50 (60)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e33 (40)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eSexually active\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e39 (47)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eGlobal cosmetic score\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e36 (44)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e46 (56)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eSex enjoyable\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e37 (45)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eSkin of breast and shoulder\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e10 (12%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eArm edema\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e12 (15%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eArm edema\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e6 (7.4%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eShoulder stiffness\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e16 (20%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eBrachial plexopathy\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e8 (10%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ePain shoulder\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e29 (35%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eShoulder stiffness\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e16 (20%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003c/div\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n\u003ctable id=\"Tab4\" border=\"1\"\u003e\u003ccaption\u003e\n\u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e\n\u003cdiv class=\"CaptionContent\"\u003e\n\u003cp\u003eUnivariate analysis of variables affecting cosmesis\u003c/p\u003e\n\u003c/div\u003e\n\u003c/caption\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eVariables\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eGood cosmesis\u003c/p\u003e\n\u003cp\u003e% (n)\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003ePoor cosmesis\u003c/p\u003e\n\u003cp\u003e% (n)\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003ep-value\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003c/thead\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eT1,2 (n\u0026thinsp;=\u0026thinsp;61)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eT3,4 (n\u0026thinsp;=\u0026thinsp;21)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e49 (30)\u003c/p\u003e\n\u003cp\u003e28 (6)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e51 (31)\u003c/p\u003e\n\u003cp\u003e72 (15)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.09\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eResected volume\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026thinsp;\u0026lt;\u0026thinsp;100 cc (n\u0026thinsp;=\u0026thinsp;41)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026thinsp;\u0026gt;\u0026thinsp;1 00cc (n\u0026thinsp;=\u0026thinsp;41)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e73 (26)\u003c/p\u003e\n\u003cp\u003e27 (10)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e33 (15)\u003c/p\u003e\n\u003cp\u003e67 (31)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e0.000\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eType of Breast Surgery\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eLumpectomy (n\u0026thinsp;=\u0026thinsp;66)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eOncoplasty (n\u0026thinsp;=\u0026thinsp;12)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eRevision surgery (n\u0026thinsp;=\u0026thinsp;4)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e27 (40.9)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e9 (75)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e-\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e39 (59.1)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e3 (25)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e4 (100)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e0.01\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eNACT (yes) n\u0026thinsp;=\u0026thinsp;25\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eNACT (no) n\u0026thinsp;=\u0026thinsp;57\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e19 (5)\u003c/p\u003e\n\u003cp\u003e54 (31)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e81 (20)\u003c/p\u003e\n\u003cp\u003e46 (26)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.003\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eBreast Volume\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMedium (n\u0026thinsp;=\u0026thinsp;48)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eLarge (n\u0026thinsp;=\u0026thinsp;34)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e71 (25)\u003c/p\u003e\n\u003cp\u003e30 (10)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e53 (23)\u003c/p\u003e\n\u003cp\u003e70 (24)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e0.08\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eBreast volume receiving 107% dose\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026thinsp;\u0026lt;\u0026thinsp;10cc, n\u0026thinsp;=\u0026thinsp;67\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026thinsp;\u0026gt;\u0026thinsp;10cc, n\u0026thinsp;=\u0026thinsp;15\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e34\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2.8 (2)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e33 (72)\u003c/p\u003e\n\u003cp\u003e28 (13)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e0.009\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eBr. volume receiving 100% dose\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026thinsp;\u0026lt;\u0026thinsp;120cc (n\u0026thinsp;=\u0026thinsp;43)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026thinsp;\u0026gt;\u0026thinsp;120cc (n\u0026thinsp;=\u0026thinsp;39)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e49 (21)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e36(14)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e51(22)\u003c/p\u003e\n\u003cp\u003e64(25)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e0.08\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eSCF RT (yes) (n\u0026thinsp;=\u0026thinsp;35)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSCF RT (No) (n\u0026thinsp;=\u0026thinsp;47)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003e66 (24)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e34 (12)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e50(23)\u003c/p\u003e\n\u003cp\u003e50(23)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.09\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003ctable id=\"Tab5\" border=\"1\"\u003e\u003ccaption\u003e\n\u003cdiv class=\"CaptionNumber\"\u003eTable 5\u003c/div\u003e\n\u003cdiv class=\"CaptionContent\"\u003e\n\u003cp\u003eLogistic regression of significant/near significant variables affecting sub-domains of cosmesis and global cosmesis\u003c/p\u003e\n\u003c/div\u003e\n\u003c/caption\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eVariables\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eBreast size\u003c/p\u003e\n\u003cp\u003ep-value, HR(CI)\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eBreast shape\u003c/p\u003e\n\u003cp\u003ep-value, HR(CI)\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eSkin breast\u003c/p\u003e\n\u003cp\u003ep-value,\u003c/p\u003e\n\u003cp\u003eHR(CI)\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eNipple position\u003c/p\u003e\n\u003cp\u003ep-value,\u003c/p\u003e\n\u003cp\u003eHR(CI)\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eScar appearance\u003c/p\u003e\n\u003cp\u003ep-value,\u003c/p\u003e\n\u003cp\u003eHR(CI)\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eGlobal cosmetic score\u003c/p\u003e\n\u003cp\u003ep-value,\u003c/p\u003e\n\u003cp\u003eHR(CI)\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003c/thead\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003ePremenopausal (R) n\u0026thinsp;=\u0026thinsp;26\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePost-meno, n\u0026thinsp;=\u0026thinsp;56\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0\u003cstrong\u003e.08(3.4)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e(0.8\u0026ndash;14)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.3(2)\u003c/p\u003e\n\u003cp\u003e(0.4\u0026ndash;10)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.9(0)\u003c/p\u003e\n\u003cp\u003e(0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.1(10)\u003c/p\u003e\n\u003cp\u003e(0.5\u0026ndash;180)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.3(1.4)\u003c/p\u003e\n\u003cp\u003e(0.4-5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.3(0.5)\u003c/p\u003e\n\u003cp\u003e(0.4\u0026ndash;1.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eNode negative (R), n\u0026thinsp;=\u0026thinsp;44\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eNode positive, n\u0026thinsp;=\u0026thinsp;38\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.8(1.4)\u003c/p\u003e\n\u003cp\u003e(0.1\u0026ndash;4.9)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.5(0.5)\u003c/p\u003e\n\u003cp\u003e(0.05\u0026ndash;4.8)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1(0.1)\u003c/p\u003e\n\u003cp\u003e(0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.2(4.6)\u003c/p\u003e\n\u003cp\u003e(0.01\u0026ndash;3.8)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.3(0.5)\u003c/p\u003e\n\u003cp\u003e(0.1-2)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003e0.06(0.3)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e(0.09\u0026ndash;1.1)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eResection vol\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026lt;\u0026thinsp;100 cc (R), n\u0026thinsp;=\u0026thinsp;41\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026gt;\u0026thinsp;1 00cc, n\u0026thinsp;=\u0026thinsp;41\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e0.06(3.8)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e(0.9\u0026ndash;16)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e0.3(2)\u003c/p\u003e\n\u003cp\u003e(0.4\u0026ndash;10)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e1(0.1)\u003c/p\u003e\n\u003cp\u003e(0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e0.4(3)\u003c/p\u003e\n\u003cp\u003e(0.2\u0026ndash;55)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e0.4(1.3)\u003c/p\u003e\n\u003cp\u003e(0.2-5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e0.005(4.6)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e(1.6\u0026ndash;13.6)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eNACT (yes) n\u0026thinsp;=\u0026thinsp;25\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eNACT (no, R), n\u0026thinsp;=\u0026thinsp;57\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.3(2)\u003c/p\u003e\n\u003cp\u003e(0.4\u0026ndash;10)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003e0.006(8.2)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e(1.8\u0026ndash;36.6)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.9(0)\u003c/p\u003e\n\u003cp\u003e(0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.3(3)\u003c/p\u003e\n\u003cp\u003e(0.2\u0026ndash;41)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003e0.009(4.4)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e(1.4\u0026ndash;13)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003e0.009(6.5)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e(1.6\u0026ndash;26)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eBr. volume 107% dose\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026thinsp;\u0026lt;\u0026thinsp;10cc, n\u0026thinsp;=\u0026thinsp;67\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026gt;\u0026thinsp;10cc, n\u0026thinsp;=\u0026thinsp;15\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e0.004(11)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e(2\u0026ndash;56)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e0.001(18)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e(3-100)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e0.19(6.7)\u003c/p\u003e\n\u003cp\u003e(0.38\u0026ndash;118)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e0.003(17)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e(3-109)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e0.06(3.8)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e(0.9\u0026ndash;16)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e0.1(5)\u003c/p\u003e\n\u003cp\u003e(0.5\u0026ndash;48)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eBr. volume 100%\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003edose\u0026thinsp;\u0026lt;\u0026thinsp;120cc, n\u0026thinsp;=\u0026thinsp;43\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026thinsp;\u0026gt;\u0026thinsp;120cc, n\u0026thinsp;=\u0026thinsp;39\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003e0.9(1.1)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e(0.09-12)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.8(0.7)\u003c/p\u003e\n\u003cp\u003e(0.06\u0026ndash;9.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1(0)\u003c/p\u003e\n\u003cp\u003e(0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.9(0)\u003c/p\u003e\n\u003cp\u003e(0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.6(0.3)\u003c/p\u003e\n\u003cp\u003e(0-4.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.6(5)\u003c/p\u003e\n\u003cp\u003e(0-4-9)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eSCF RT (yes)n\u0026thinsp;=\u0026thinsp;35\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSCF RT (No, R), n\u0026thinsp;=\u0026thinsp;47\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003e0.06(0.28)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e(0.07-1)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.4(0.5)\u003c/p\u003e\n\u003cp\u003e(0.09\u0026ndash;2.9)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.9(0)\u003c/p\u003e\n\u003cp\u003e(0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.1(0.1)\u003c/p\u003e\n\u003cp\u003e(0.01-.15)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.1(0.4)\u003c/p\u003e\n\u003cp\u003e(0.1\u0026ndash;1.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.5(0.7)\u003c/p\u003e\n\u003cp\u003e(0.1\u0026ndash;1.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec2\" class=\"Section2\"\u003e\n\u003ch2\u003eFactors predicting late-effects in arm and shoulder:\u003c/h2\u003e\n\u003cp\u003eAssessment of LE by physician revealed skin changes in breast and shoulder in 12% patients, brachial plexopathy in 4%, shoulder stiffness in 20% and arm oedema in 6% while according to PROM shoulder and arm pain was found in 35%, shoulder stiffness in 20% and arm oedema in15%. On multivariate analysis of factors affecting physician assessed LE in arm and shoulder, tumour size had a trend toward significance (HR 9) for arm oedema, volume of breast receiving 107% had a significant impact on brachial plexopathy (HR 6.1) and shoulder stiffness (HR 4). Presence of comorbidity also affected shoulder stiffness (HR 3.9) (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e6\u003c/span\u003e).\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003ctable id=\"Tab6\" border=\"1\"\u003e\u003ccaption\u003e\n\u003cdiv class=\"CaptionNumber\"\u003eTable 6\u003c/div\u003e\n\u003cdiv class=\"CaptionContent\"\u003e\n\u003cp\u003eLogistic regression of significant /near significant variables affecting late-effects in arm and shoulder.\u003c/p\u003e\n\u003c/div\u003e\n\u003c/caption\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eVariables\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eArm edema\u003c/p\u003e\n\u003cp\u003eP-value,HR(CI)\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eBrachial plexopathy\u003c/p\u003e\n\u003cp\u003ep-value,HR(CI)\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eShoulder stiffness,\u003c/p\u003e\n\u003cp\u003eP-value,HR(CI)\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eSkin arm, shoulder\u003c/p\u003e\n\u003cp\u003ep-value,HR(CI)\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003c/thead\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eComorbidity (no,R) (n\u0026thinsp;=\u0026thinsp;65)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eComorbidity (yes) (n\u0026thinsp;=\u0026thinsp;17)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.3(0.2)\u003c/p\u003e\n\u003cp\u003e(0.02-1)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003e0.06(0.2)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e(0.04-1)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003e0.07 (4.8)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e(0.6\u0026ndash;8.7)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.13(3)\u003c/p\u003e\n\u003cp\u003e(0.7\u0026ndash;13)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eT\u0026thinsp;\u0026lt;\u0026thinsp;3cm (R) (n\u0026thinsp;=\u0026thinsp;59)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eT\u0026thinsp;\u0026gt;\u0026thinsp;3cm, (n\u0026thinsp;=\u0026thinsp;23)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003e0.09(7.2)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e(0.6\u0026ndash;76\u003c/strong\u003e)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.2(0.3)\u003c/p\u003e\n\u003cp\u003e(0.4\u0026ndash;3.7)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.6 (1.3)\u003c/p\u003e\n\u003cp\u003e(0.3\u0026ndash;5.7)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.4(2.2)\u003c/p\u003e\n\u003cp\u003e(0.3\u0026ndash;16)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eVolume receiving 107%\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026lt;\u0026thinsp;10cc (n\u0026thinsp;=\u0026thinsp;67)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026gt;\u0026thinsp;10cc (n\u0026thinsp;=\u0026thinsp;15)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e0.9 (0)\u003c/p\u003e\n\u003cp\u003e(0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e0.03(6.1)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e(1.1\u0026ndash;33.5)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e0\u003cstrong\u003e.07(4)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e(0.8\u0026ndash;18)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e0.2 (2.8)\u003c/p\u003e\n\u003cp\u003e(0.4\u0026ndash;18)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e\u003cstrong\u003eFactors predicting PROM\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePatients reported breast pain in 35%, breast oedema in 11%, breast sensitivity in 15%, change in skin of breast in 64%. Sexual parameters like sexual interest was present in 46%, 47% were sexually active and sex was enjoyable in 45%. The log transformed systemic symptom score was poor in 34% women, arm score was poor in 33%, breast score was poor in 27%, and hair loss was bothersome for 75% women. Body image perception was poor in 69% women, sexual function and enjoyment was poor in 30% and 25% women and 80% of them were bothered about their future. On multivariate analysis of factors affecting symptom and functional scales, postmenopausal status was associated with higher arm score, breast score, hair loss, and sexual function decline. Node positive status was also associated with higher arm score. High breast volume and premenopausal status had a trend towards higher breast score. T size more than 3 cm and receipt of SCF RT shows significantly higher altered body image (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e7\u003c/span\u003e,8 Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003es).\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003ctable id=\"Tab7\" border=\"1\"\u003e\u003ccaption\u003e\n\u003cdiv class=\"CaptionNumber\"\u003eTable 7\u003c/div\u003e\n\u003cdiv class=\"CaptionContent\"\u003e\n\u003cp\u003eLogistic regression of significant/near significant variables affecting PROM.\u003c/p\u003e\n\u003c/div\u003e\n\u003c/caption\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n\u003cth colspan=\"4\" align=\"left\"\u003e\n\u003cp\u003eSymptom scale (p value, (HR))\u003c/p\u003e\n\u003c/th\u003e\n\u003cth colspan=\"4\" align=\"left\"\u003e\n\u003cp\u003eFunctional scale (p value, (HR))\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eVariables\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eSystemic score\u003c/p\u003e\n\u003cp\u003e21\u0026thinsp;\u0026plusmn;\u0026thinsp;14.6\u003c/p\u003e\n\u003cp\u003e(0\u0026ndash;85)\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eArm score\u003c/p\u003e\n\u003cp\u003e15\u0026thinsp;\u0026plusmn;\u0026thinsp;21\u003c/p\u003e\n\u003cp\u003e(0\u0026ndash;77)\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eBreast score\u003c/p\u003e\n\u003cp\u003e15\u0026thinsp;\u0026plusmn;\u0026thinsp;12\u003c/p\u003e\n\u003cp\u003e(0\u0026ndash;66)\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eHair loss\u003c/p\u003e\n\u003cp\u003e31\u0026thinsp;\u0026plusmn;\u0026thinsp;24\u003c/p\u003e\n\u003cp\u003e(0-100)\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eBody image\u003c/p\u003e\n\u003cp\u003e80\u0026thinsp;\u0026plusmn;\u0026thinsp;22\u003c/p\u003e\n\u003cp\u003e(16\u0026ndash;100)\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eSexual function\u003c/p\u003e\n\u003cp\u003e75\u0026thinsp;\u0026plusmn;\u0026thinsp;27\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eSexual enjoyment\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eFuture\u003c/p\u003e\n\u003cp\u003e66\u0026thinsp;\u0026plusmn;\u0026thinsp;22\u003c/p\u003e\n\u003cp\u003e(0-100)\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003ePremenopausal (R) (n\u0026thinsp;=\u0026thinsp;26)\u003c/p\u003e\n\u003cp\u003ePostmenopausal, (n\u0026thinsp;=\u0026thinsp;56)\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003e0.1(6.2)\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003e0.03 (4.9)\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003e0.03 (7.3)\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003e0.03 (7.3)\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003e0.5(1.6)\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003e0.02(5.8)\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003e0.02(5.8)\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003e0.5(1.7)\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003c/thead\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eT\u0026thinsp;\u0026lt;\u0026thinsp;3cm (R) (n\u0026thinsp;=\u0026thinsp;59)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eT\u0026thinsp;\u0026gt;\u0026thinsp;3cm, (n\u0026thinsp;=\u0026thinsp;23)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.5(1.6)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.18(0.13)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.5(0.29)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.5 (0.2)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003e0.07 (3.2)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.3(2.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.5(2.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.3(0.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eNode negative (R), (n\u0026thinsp;=\u0026thinsp;44)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eNode positive, (n\u0026thinsp;=\u0026thinsp;38)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.5(1.8)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003e0.07 (4.3)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.35 (2.8)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.3 (2.2)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.8(1.2)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.1(0.2)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.1(0.2)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.7(1.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eBreast Volume\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMedium (R), (n\u0026thinsp;=\u0026thinsp;42)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eLarge, (n\u0026thinsp;=\u0026thinsp;40)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e.09 (3.6)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.7(0.7)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003e.07 (5.4)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003e0.07 (7.4)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.4(0.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.7(1.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.7(1.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.8(0.8)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eSCF RT (yes) (n\u0026thinsp;=\u0026thinsp;35)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSCF RT (No) (n\u0026thinsp;=\u0026thinsp;47)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.9 (0.9)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e\u003cstrong\u003e0.09(0.2)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.13 (0.17)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.2(1.8)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e\u003cstrong\u003e0.02(0.1)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.9(1)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.9 (1)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.1(0.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003c/div\u003e\n\u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eOne of the important endpoints of successful implementation of breast conservation is cosmesis. The standard of care for cosmesis assessment is clinical assessment, which we were able to conduct in 82 patients during the period November 2020 to September 2021.Since we investigated women with a median follow-up of 5 years, a cross-sectional study is adequate, as any further change in cosmesis is usually not observed after 3 years of RT completion. After invitation with several rounds of phone calls only 46% patients participated in this study and the rest could not be contacted due to change in phone number or non-receipt of calls (40%), due to death (9%), and the reluctance to visit OPD due to Covid.\u003c/p\u003e \u003cp\u003eClinicians are able to assess the breast with a 3-D view whereas this is not possible with standard photographs. Varying thresholds of experience in grading toxicity between clinicians can lead to interobserver variability which we did not face because both the clinicians conducted the CA of the same patient together. We did not indulge in complex methods of cosmetic assessment like BCTOS or use of BCCT software because these cannot be used in the clinic daily even though they are more accurate.\u003c/p\u003e \u003cp\u003eMost of the reported cosmesis studies of hypofractionation are in patients with early-stage tumours while our study comprised of patients with high-risk features like T2 or more [95%], node positive [50%], chemotherapy [97%] and SCF RT [43%]. In START B, 70% patients were T1, 72% were node negative and any change in breast appearance (mild or marked) at 5 years recorded using the consensus scores was seen in only 39.3%. The incidence of poor cosmesis by physician assessment was 38% with hypofractionation as compared to 44% with conventional fractionation [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. This incidence of poor cosmesis by physician assessment increased to 43% with hypo-fractionated boost as compared to 50% with conventional fractionation boost. In our series all patients received boost and with the presence of high-risk features the incidence of adverse cosmesis was 56%. Similar observations of poor cosmesis have been observed with hypo-fractionated RT in women with high-risk features in 61% [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Administration of CT has been reported to be associated with worse cosmesis [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. The EORTC study reported significant association of the risk of moderate to severe fibrosis with administration of CT and or tamoxifen in premenopausal or postmenopausal women respectively. The DBCG group observed excellent to good cosmesis in only 50% patients in a population of patients with predominantly T1 tumours (80%) treated with conventional fractionation, where apart from physician assessment, nipple position was also ascertained with BCCT.core software [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Conventional fractionation has been found to result in poor cosmesis as compared to hypofractionation [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eApart from high-risk features, the surgical factors contributing to high incidence of adverse cosmesis in our patients was large resection volumes (\u0026gt;\u0026thinsp;100cc) in approximately 50% patients which is a reflection of 37% tumours being more than 3 cm. In a study of CA in 598 early breast cancer, the resection of 70 cc or more of breast tissue was more common among the failed patients than among matched patients with good or excellent cosmesis [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. For safe and cosmetically acceptable breast-conserving therapy in patients with large breast cancers, the tumour volume should be reduced preoperatively by NACT, and lost tissue volume should be replaced after wide local excision by oncoplastic techniques. During the period of assessment in the index study, only 12 patients with oncoplastic technique turned up for CA and the cosmetic outcome of these patients was good in 75% patients as compared to good cosmesis in 44% patients who underwent non-oncoplasty surgery. As more oncoplastic techniques are gradually being adopted by our surgeons, the cosmesis rate is likely to improve in near future.\u003c/p\u003e \u003cp\u003eThe radiotherapy related factors which contributed to poor cosmesis were large breast volume, volume of breast receiving 107% or more dose, and volume of breast receiving 100% / 95% dose. In our series we estimated the surrogate of breast volume (from treatment planning scan) ie the volume encompassed by 50% isodose as mentioned in IMPORT Low [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. They reported a median volume of 778 cc, 1114 cc and 1357 cc as cut-off volumes for small, medium and large breast when corelated with cup size. Since our series was a retrospective analysis and we did not have the previous bra cup size of our patients to correlate with breast volumes, we sought to correlate with published data. In our series we adopted the cut-off value of 1800 cc (instead of mean value of 1600cc with which no correlation was found) and got a correlation of adverse cosmesis with increase in breast volume beyond 1800cc. Yarnold et al reported a hazard ratio of 1.8 for poor cosmesis in patients receiving 100% dose to more than 42% volume of breast while we found a HR of 12 [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Similar findings have been reported by Mukesh et al., who found improved dose homogeneity with simple IMRT which translated into superior overall cosmesis and reduction in the risk of skin telangiectasia [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Surprisingly boost PTV volume (\u0026gt;\u0026thinsp;100cc) did not significantly affect cosmesis in our series as reported by Young Boost trial, where the cosmesis was poor if the boost dose was more than 16 Gy, boost volume was high and photon boost was given [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. Nodal positivity mandates RT to SCF with or without axillary RT depending on the risk factors. We observed higher incidence of adverse cosmesis in women who received RT to SCF (HR 0.7). Similar findings have been reported in a study where 89% of patients treated with a tangent pair technique had excellent results at 5 years when treated with tangential beams alone as compared with 69% of patients treated with tangents and SCF RT [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. SCF RT has also been found to contribute to poor cosmesis in some studies with hypofractionation [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe other factors which resulted in poor cosmesis were postmenopausal status (60%), upper outer quadrant tumours. Though the literature suggests adverse cosmesis in inner quadrant and central tumours, our series had low numbers of other quadrant tumours (only 25%) [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eAmongst the various domains which contributed to global cosmesis, the most significant factors affecting global cosmesis were breast size, shape and nipple position. Breast size is a surrogate of resection volume and hence alteration of this domain is expected to impact global cosmesis, which is what we observed in our series also. Secondly high resection volume will also alter the shape and nipple position so these subdomains also impacted global cosmesis in our series.\u003c/p\u003e \u003cp\u003eRegarding late-effects, tumour size more than 3 cm was a significant factor contributing to arm oedema (6%). Sentinel LN procedure led to lower (4.3%) incidence of arm oedema as compared to 9% with axillary clearance. Factors significantly impacting brachial plexopathy and shoulder stiffness were presence of comorbidity and volume of breast receiving 107% dose. The START trial reported an incidence of 8% arm edema, 18% shoulder stiffness with hypofractionation as compared to 6% and 8% with conventional fractionation. The Danish study of early BC treated with conventional fractionation reported that the number of positive axillary nodes\u0026thinsp;\u0026gt;\u0026thinsp;10 and axillary RT increased the arm oedema rate from 7\u0026ndash;28%, arm pain from 13\u0026ndash;28%, shoulder stiffness from 0 to 8% [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. Their 10year follow-up study stated that 64% patients had one or more subjective loco regional symptoms like pain, swelling of the arm, and decreased shoulder mobility. In our series higher LE in arm and shoulder was observed in those who received SCF RT (26% shoulder stiffness versus 18%) which is comparable to the literature.\u003c/p\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003ePatient reported Outcome measures:\u003c/h2\u003e \u003cp\u003eAs an increasing number of successfully treated patients have to deal with the results of local treatment on a daily basis, self-reported cosmetic outcome and satisfaction have become critical endpoints of BCT. Since the BR23 questionaire does not capture data pertaining to cosmesis, a direct ascertainment of patient reported cosmesis is not possible, but an indirect assessment was done from breast score and body image. Though the breast score was poor in 26% women in the index study, their perception of the body image was poor in 69%. There is enough data which states that women who were dissatisfied with their cosmetic results had an impaired body image. Data from START reported 20% incidence of patient reported poor cosmesis with 2 field hypo-fractionated breast RT in early BC. Breast pain can result from injury to muscle and ligaments and is more likely to be transient as compared to persistent neuropathic pain due to damage to the nerve tissue. This affects QOL in survivors and was present in 33% women in the index study. Similarly 40% women had marked symptoms in arm and shoulder and one third had breast symptoms, while incidence of same was 20% and 33% in START trials [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. In the index study, arm score had correlation with positive nodal status (HR 4.3), and breast score with breast volume (\u0026gt;\u0026thinsp;1600cc) (HR 5.4) and premenopausal status (HR 7.3) which has been reported in literature also [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eSexual dysfunction is common in breast cancer survivors and has been found to be associated with feeling of emotional separation in couples, fear of sexual intercourse, lower emotional functioning, poorer body image or co-morbidities [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. In our series only 70% women were sexually active or found it enjoyable, and this was more adversely affected in premenopausal women.\u003c/p\u003e \u003cp\u003eThe START and IMPORT trial results reveal that PROMs could potentially replace either CA or photographs to assess cosmesis since patients rate their subjective satisfaction with an experience of a range of breast changes, whilst clinicians seek objective adverse treatment effects. Since CA are still widely used all over the globe, an alternative viewpoint is that both PROMs and CAs are necessary as they measure differing aspects of disease experience and are complementary.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eLIMITATIONS\u003c/h2\u003e \u003cp\u003eThe main limitation of our study was only 46% attendance of BCS patients for cosmesis evaluation because of various reasons mentioned earlier. The other limitation of our study was that the BR 23 questionaire does not directly evaluate PR cosmesis, rather variables assessing change in skin appearance, firmness in the area of the affected breast, asymmetry and distortion and shrinkage of breast as used for START trial would have captured adequate information for PR cosmesis.\u003c/p\u003e \u003c/div\u003e"},{"header":"CONCLUSIONS","content":"\u003cp\u003eThe presence of high-risk features in 50% women in our population resulted in higher incidence of adverse global cosmesis, LE and PROMs.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eThe authors declare that no funds, grants, or other support were received during the preparation of this manuscript.\u003c/p\u003e\n\u003cp\u003eThe authors affirm that human research participants provided informed consent for publication of the images in Figure 1.\u003c/p\u003e\n\u003cp\u003eAll authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by [Chandrashekhar Mishra], [Sushma Agrawal]. The first draft of the manuscript was written by [Sushma Agrawal] and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets generated during and/or analysed during the current study are not publicly available due to Institute policy but are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Institute Ethics Committee of University B (Date 2.9.20./No2018-82-IP-EXP).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent to participate\u003c/strong\u003e:\u003c/p\u003e\n\u003cp\u003e\u0026ldquo;Informed consent was obtained from all individual participants included in the study.\u0026rdquo;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003eNon-funded study.\u003c/p\u003e\n\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eCM: collected patient data wrote the manuscriptSA: treated patients, contributed to data, and analysed data and wrote the manuscriptPL: treated patients and contributed to data.GC: treated patients and contributed to data.GA: treated patients and contributed to data.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eWhelan T, MacKenzie R, Julian J, Levine M, Shelley W, Grimard L, et al. Randomized trial of breast irradiation schedules after lumpectomy for women with lymph node‑negative breast cancer. J Natl Cancer Inst 2002; 94:1143‑50. DOI: 10.1093/jnci/94.15.1143 \u003c/li\u003e\n\u003cli\u003eSTART Trialists\u0026rsquo; Group, Bentzen SM, Agrawal RK, Aird EG, Barrett JM, Barrett‑Lee PJ, et al. The UK standardisation of breast radiotherapy (START) trial B of radiotherapy hypofractionation for treatment of early breast cancer: A randomised trial. Lancet 2008; 371:1098‑107. doi: 10.1016/S0140-6736(08) 60348-7.\u003c/li\u003e\n\u003cli\u003eSmith BD, Bellon JR, Blitzblau R, Freedman G, Haffty B, Hahn C, Halberg F, Hoffman K, Horst K, Moran J, Patton C, Perlmutter J, Warren L, Whelan T, Wright JL, Jagsi R. Radiation therapy for the whole breast: Executive summary of an American Society for Radiation Oncology (ASTRO) evidence-based guideline. Pract Radiat Oncol. 2018 8(3):145-152. DOI: 10.1016/j.prro.2018.01.012 \u003c/li\u003e\n\u003cli\u003eKrug D, Baumann R, Combs SE, Duma MN et al. Moderate hypofractionation remains the standard of care for whole-breast radiotherapy in breast cancer: Considerations regarding FAST and FAST-Forward. Strahlenther Onkol. 2021;197(4):269-280. DOI: 10.1007/s00066-020-01744-3 \u003c/li\u003e\n\u003cli\u003eRajan Yadav, Punita Lal, Sushma Agarwal, Shagun Misra, Mranalini Verma, K. J. Maria Das, S. K. Senthil Kumar, Anup Kumar, S. K. Mishra, Amit Agarwal, Gaurav Agarwal, Anjali Mishra, Gyan Chand, AK. Verma, Shaleen Kumar. Comparative retrospective analysis of locoregional recurrence in unselected breast cancer patients treated with conventional versus hypo-fractionated radiotherapy at a tertiary cancer center? Journal of Cancer Research and Therapeutics. 2020.16(6):1314-1322. DOI: 10.4103/jcrt.JCRT_389_18 \u003c/li\u003e\n\u003cli\u003eAgarwal G, Ramakant P.Breast Cancer Care in India: The Current Scenario and the Challenges for the Future. Breast Care (Basel).2008 3(1):21-27. doi:10.1159/000115288\u003c/li\u003e\n\u003cli\u003eHaviland JS, Hopwood P, Mills J, Sydenham M et al. Do patient reported outcome measures agree with clinical and photographic assessments of normal tissue effects after breast radiotherapy? The experience of the standardisation of breast radiotherapy (START) trials in early breast cancer. Clin Oncol 2016.;28:345\u0026ndash;53. doi:10.1016/j.clon.2016.01.011.\u003c/li\u003e\n\u003cli\u003eTabassum Wadasadawala, Shwetabh Sinha, Vani Parmar et al. Comparison of subjective, objective and patient‑reported cosmetic outcomes between accelerated partial breast irradiation and whole breast radiotherapy: a prospective propensity score‑matched pair Analysis. Breast Cancer, 2020; \u003cstrong\u003e27\u003c/strong\u003e:206\u0026ndash;212. doi.org/10.1007/s12282-019-01009-7.\u003c/li\u003e\n\u003cli\u003eBudrukkar AN, Sarin R, Shrivastava SK, Deshpande DD, Dinshaw. Cosmesis, late sequelae and local control after breast-conserving therapy: influence of type of tumour bed boost and adjuvant chemotherapy. Clin Oncol (R Coll Radiol) . 2007;19(8):596-603.DOI: 10.1016/j.clon.2007.06.008 \u003c/li\u003e\n\u003cli\u003eChristina D Lyngholm\u003csup\u003e \u003c/sup\u003e, Peer M Christiansen, Tine E Damsgaard, Jens Overgaard. Long-term follow-up of late morbidity, cosmetic outcome and body image after breast conserving therapy. A study from the Danish Breast Cancer Cooperative Group (DBCG). Acta Oncol 2013;52(2):259-69. DOI: 10.3109/0284186X.2012.744469 .\u003c/li\u003e\n\u003cli\u003eReshma Jagsi, MD, Kent A. Griffith, Frank Vicini, et al. Toward Improving Patients\u0026rsquo; Experiences of Acute Toxicity From Breast Radiotherapy: Insights From the Analysis of Patient-Reported Outcomes in a Large Multicenter Cohort. J Clin Oncol 2020; 38:4019-4029.\u003c/li\u003e\n\u003cli\u003eOlivotto IA, Rose MA, Osteen RT, et al. Late cosmetic outcome after conservative surgery and radiotherapy: analysis of causes of cosmetic failure. Int J Radiat Oncol Biol Phys. 1989;17:747e753. DOI: 10.1016/0360-3016(89)90061-8 \u003c/li\u003e\n\u003cli\u003eBhattacharya IS, Haviland JS, Hopwood P et al. Can patient-reported outcomes be used instead of clinician-reported outcomes and photographs as primary endpoints of late normal tissue effects in breast radiotherapy trials? Results from the IMPORT LOW trial. Radiother Oncol. 2019 134:220-230. doi: 10.1016/j.radonc.2019.01.036.\u003c/li\u003e\n\u003cli\u003eChristy Goldsmith, Joanne Haviland, Yat Tsang et al. Large breast size as a risk factor for late adverse effects of breast radiotherapy: Is residual dose inhomogeneity, despite 3D treatment planning and delivery, the main explanation? Radiotherapy and Oncology 100:236-240 doi:10.1016/j.radonc.2010.12.012\u003c/li\u003e\n\u003cli\u003eMukesh MB, Qian W, Wah Hak CC, Wilkinson JS, Barnett GC, Moody AM, et al. Breast Intensity-modulated Radiotherapy Trial: Comparison of Clinician versus Patient-reported Outcomes. Clin Oncol (Royal College of Radiologists (Great Britain)) 2016;28:354\u0026ndash;64.DOI: 10.1016/j.clon.2016.02.011 \u003c/li\u003e\n\u003cli\u003eBrouwers PJAM, van Werkhoven E, Bartelink H et al. Predictors for poor cosmetic outcome in patients with early stage breast cancer treated with breast conserving therapy: Results of the Young boost trial. Radiother Oncol.2018;128(3):434441. doi:10.1016/j.radonc.2018.06.020. \u003c/li\u003e\n\u003cli\u003eDi Wang, Xiaofeng Yang, Jiabei He et al. The Impact of Regional Nodal Irradiation and Hypo-fractionated Whole Breast Radiation on Long Term Breast Retraction and Poor Cosmetic Outcome in Breast Cancer Survivors. Clinical Breast Cancer. 2020; 2020 Feb;20(1):e75-e81\u003c/li\u003e\n\u003cli\u003eDavid Peterson\u003csup\u003e \u003c/sup\u003e, Pauline T Truong\u003csup\u003e \u003c/sup\u003e\u003csup\u003e \u003c/sup\u003e, Sameer Parpia\u003csup\u003e \u003c/sup\u003e, Ivo A Olivotto. Predictors of adverse cosmetic outcome in the RAPID trial: an exploratory analysis , Int J Radiat Oncol Biol Phys . 2015;91(5):968-76. DOI: 10.1016/j.ijrobp.2014.12.040 \u003c/li\u003e\n\u003cli\u003eKatrine Rye Hauerslevhttps, Anders Husted Madsenb, Jens Overgaard, Tine Engberg Damsgaarda, and Peer Christiansen. Long-term follow-up on shoulder and arm morbidity in patients treated for early breast cancer. Acta Oncologica 2020; 59 (7):851-858.DOI: \u003c/li\u003e\n\u003cli\u003eWhite J, Joiner MC. Toxicity from radiation in breast cancer. Cancer Treat Res 2006; 128:65-109. DOI:10.1007/0-387-25354-8_5 \u003c/li\u003e\n\u003cli\u003eAnne Bredart S Dolbeault, A Savignoni etal. Prevalence and associated factors of sexual problems after early-stage breast cancer treatment: results of a French exploratory survey. Psycho-oncology 2011:20(8):841-50. doi: 10.1002/pon.1789.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"large operable, locally advanced breast cancer, Brest conservation, cosmesis, late effects, patient reported outcome measures","lastPublishedDoi":"10.21203/rs.3.rs-3836655/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3836655/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eIntroduction\u003c/strong\u003e:\u003c/p\u003e\n\u003cp\u003eLiterature on cosmesis in large operable (LO) and locally advanced breast cancer (LABC) is sparse, so we investigated the cosmesis, LE and PROM and factors affecting it in this subset.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMaterials and Methods\u003c/strong\u003e:\u003c/p\u003e\n\u003cp\u003eBC with upfront BCS or after neoadjuvant chemotherapy (NACT) underwent physical CA, LE and PROM using EORTC, RTOG and BR23 questionnaire respectively. Patient, tumour and treatment related factors were correlated with CA, LE and PROM by univariate and multivariate analysis.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e186 women underwent BCS, but only 82 could participate due to Covid. Prevalence of high-risk features were found: \u0026gt;3cm tumour in 37%, 50% node positive, 100% received CT, grade 3 in 57%, Her-2/TNBC in 70%. At a median follow-up of 5 years, we found that 56% patients had adverse global cosmesis. Factors responsible for adverse cosmesis were tumour size [\u0026gt; 3 cm, HR 2.3], node positivity [HR 0.3], receipt of CT [HR 6.5], large resection volumes [HR 4.6], large breast volume [HR 1], supraclavicular RT in 43% [HR 0.7]. Dosimetric factors found significant for adverse cosmesis were breast volume receiving 107% dose (\u0026gt; than 10cc, HR 5) and breast volume receiving 100% dose (\u0026gt; than 120cc, HR 5). The incidence of arm oedema was 6%, shoulder stiffness 20%, brachial plexopathy 4% and factors significant for LE were tumour size \u0026gt; 3cm [HR 9], breast volume receiving 107% [HR 6], and co-morbidity [HR 3]. 69% had poor body image, 35% breast pain, 47% were sexually active.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eBC with LO/LABC and high-risk features had adverse cosmesis in 56% women.\u003c/p\u003e","manuscriptTitle":"Factors predicting Cosmesis (CA), Late effects (LE) and Patient reported outcome measures (PROM) in high-risk breast cancer (BC) treated with hypo-fractionated radiotherapy (HF-WBI): real world outcomes from a developing country","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-01-08 19:52:37","doi":"10.21203/rs.3.rs-3836655/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"5897f2cb-b7ce-4c63-854a-047b8297e3a2","owner":[],"postedDate":"January 8th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-01-09T21:44:10+00:00","versionOfRecord":[],"versionCreatedAt":"2024-01-08 19:52:37","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-3836655","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3836655","identity":"rs-3836655","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}