Editorial for "Real World Safety of Adjuvant Ultra Hypofractionated Radiotherapy in Nonmetastatic Breast Cancer: Acute Cutaneous Toxicity and Aesthetic Outcomes".

Real World Safety of Adjuvant Ultra Hypofractionated Radiotherapy in Nonmetastatic Breast Cancer: Acute Cutaneous Toxicity and Aesthetic Outcomes.

WITHDRAWN: Editorial for "Real World Safety of Adjuvant Ultra Hypofractionated Radiotherapy in Nonmetastatic Breast Cancer: Acute Cutaneous Toxicity and Esthetic Outcomes".

Background: Breast cancer (BC) management in older women requires an individual approach and is becoming increasingly topical given the aging population. Postoperative radiation therapy (RT) is a standard treatment of BC after breast-conserving-surgery in most patients but its relative benefit may be counteracted by potential side-effects, especially in elderly. The aim of this study was to assess acute and long-term radiation-induced toxicities and the impact of comorbidities on outcomes in the older women treated by RT for non-metastatic breast cancer. Materials and Methods: Women aged ≥ 70 years at diagnosis, who received exclusive or postoperative RT for primary non-metastatic breast cancer, including carcinoma in situ, between 2003 and 2009 were retrieved from the Institut Curie registry. We calculated the Charlson Comorbidity Index (CCI) for each patient and collected the cardiovascular risk factors other than age (hypertension, dyslipidemia, smoking status). We analyzed overall survival (OS), progression free survival (PFS) and acute and late toxicities according to the CTCAE (Common Terminology Criteria for Adverse Events) v3.0. Results: A total of 817 patients was included in this study. Median age at diagnosis was 76.6 years [70 – 93.3]. Most patients had HR+ (hormone-receptor positive) HER2- breast cancer (83.9 %). 517 patients (62.7%) had at least one cardiovascular risk factor. With a median follow-up of 6.7 years [0.5 - 13], OS at 5 years was 86.3% CI95%[83.8 - 88.8], and PFS was 84.5% CI95%[81.9 – 87.1]. OS at 5 years was statistically different according to the Charlson index: 90.2% CI95%[87.2 – 93.3] for a CCI of 0, 84.6 % CI95%[80.5 – 88.8] for a CCI of 1, and 78% CI95%[70.5 – 86.2] for a CCI ≥ 2 (p < 0.001, log-rank test), respectively. Similar results were found for PFS (p < 0.001, log-rank test). 22.6% of patients had no toxicity; of those who experienced toxicity, most was limited to grade I or II. Only five cases (0.6%) of radiation – induced pneumonitis were reported after a median time of 16.4 months (grade I, n = 1; grade II, n = 2). One case (0.1%) of myocardial ischemia was described 14.5 months after RT. Women older than 80 years were less likely to have acute dermatitis (OR = 0.62; CI95%[0.45 - 0.85]), long-term breast pain (OR = 0.31; CI95%[0.14 - 0.62]), and long-term breast deformation (OR = 0.63; CI95%[0.42 - 0.93]) compared to patients younger than 80 years. There was no significant association found between other cardiovascular risk factors and toxicities. Conclusion: Radiation therapy for breast cancer in the older women is well-tolerated. An extended follow-up is planned in order to assess toxicities at a longer time horizon. Further studies could be envisaged to assess the quality-of-life during and after RT for breast cancer in the older patient population. Citation Format: Cao KI, Salviat F, Fourquet A, Falcou M-C, Laki F, Beuzeboc P, Savignoni A, Bazire L, Poortmans P, Kirova YM. Tolerability and outcomes of radiation therapy for breast cancer in older women: A retrospective study in 817 patients [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P2-11-20.

Real World Safety of Ultra Hypofractionated Radiotherapy for Breast Cancer: Acute Cutaneous Toxicity and Aesthetic Outcomes in a Tunisian Prospective Study

Introduction: This study aimed to assess the efficacy, tolerance and impact of comorbidities on outcomes in older women treated by exclusive radiation therapy (RT) for non-metastatic breast cancer (BC). Material and methods: We studied retrospectively female patients older 70 years at diagnosis, treated by exclusive RT for their BC between 2003 and 2013 in our Department. We analysed overall survival (OS), progression free survival (PFS), and specific survival (SS). Comorbidities were evaluated with the Charlson Comorbidity Index (CCI), and toxicities with the CCTCAE v3.0. Results: Between 2003 and 2013, there were 978 patients older than 70 treated for BC in our Hospital, and 817 received RT. Hypofractionated RT was delivered in 90.2% of patients. Of them, 66 patients underwent exclusive RT after refusal of surgery. The median age was 84.8 [71.3-91.7]. The median follow-up was 51.9 months [0.5- 99]. OS, SS and PFS at 5 years were 65.5% CI 95% [54.1-79.3], 86.3% CI 95% [77.2-96.4]), and 58.4% CI 95% [46.9-72.7], respectively. Five-year OS was statistically different according to age younger or older than 85 years: 72.9% CI 95% [58.4-91.1] and 57.1%, IC 95% [40.8-79.8], (p = 0.0026). Similar results were found for 5-year PFS: 64.5% CI 95% [49.5-84.1] and 51.6% CI 95% [35.8-74.5] (p = 0.014). The 5-year OS was also statistically different according to CCI score, respectively 70.8% CI 95% [57.0-87.9] and 59.8% CI 95 % [42.4-84.3] (p = 0.039) for a score of 0 or ≥ 1. Median CCI score was 1. There were 10.6% of the patients who experienced no toxicities; there were 59% who presented grade 1 and 2 radiodermatitis. Late toxicities were mainly fibrosis, observed in 39.4% of the patients, mostly of grade 1 and 2.Conclusion: Exclusive radiation therapy for non-metastatic BC in older women is feasible and well tolerated when adapted techniques are used, but the prognostic is strongly impacted by age and comorbidities. Citation Format: Lorraine Waechter, Kim Cao, Matthieu Carton, Youlia Kirova, Alain Fourquet. Outcomes of exclusive radiation therapy for breast cancer in older women according to age and comorbidity status: An observational retrospective study [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P4-12-12.

Radiation therapy (RT) is a standard treatment for non-metastatic breast cancer and is associated with acute and late toxicities. Intensity-modulated RT (IMRT) may decrease toxicity and is convenient for patients. To assess the efficacy and safety of IMRT in women with early stage breast cancer. Systematic review study; Multi-institutional centers. Seven databases were searched. Randomized controlled trials (RCT) comparing IMRT with any "non-IMRT" strategies were included. Primary outcomes were local control and acute toxicity. Cochrane Handbook was use to plan and conduct the review, and PRISMA 2020 was used to report results. Five RCT involving 2,556 women (n = 1,283 IMRT; n = 1,274 control arm) were included. Baseline characteristics were similar between trials and arms. Local relapse-free survival rates were not different (hazard-ratio [HR] 0.62; 95%confidence interval [CI] -0.38 to 1.62; P > 0.05); however, IMRT reduced the overall acute toxicity (RR 0.69, 95%CI 0.58 to 0.82; P < 0.00001) and acute moist desquamation (risk-ratio [RR] 0.71, 95%CI 0.60 to 0.82; P < 0.00001). Lymphedema and pneumonitis rates, and survival outcomes were not affected by IMRT. The 2-year telangiectasia rate was decreased with IMRT (RR 0.66, 95%CI 0.47 to 0.93; P = 0.02); however, edema, pain, pigmentation, or fibrosis remained unaffected. IMRT did not improve cosmesis. IMRT improved acute toxicity and lowered telangiectasia rates, without affecting oncological and aesthetic outcomes. This review was registered at Cochrane Database of Systematic Reviews 2013, Issue 3. Art. No.: CD010420. https://doi.org/10.1002/14651858.CD010420.

Impact of Collagen Vascular Disease on Radiation-Related Toxicity in Breast Cancer Patients: A Matched Pair Analysis

Background and Purpose: Recent phase 3 clinical trials have evaluated the addition of bevacizumab (B) to standard chemotherapy in the treatment of patients with non-metastatic breast cancer. But few data are available about the tolerance of B with locoregional radiation therapy (RT). The objective was to evaluate the 5 years late toxicities of the concurrent B and RT in non-metastatic breast cancer. Material and methods: This is a multicenter prospective study including non-metastatic breast cancer patients enrolled in phase 3 clinical trials evaluating B with concurrent RT (BEATRICE, BETH, BEVERLY 1, BERVERLY 2) versus RT alone. All patients received neo-adjuvant or adjuvant chemotherapy and normo-fractionated breast or chest wall RT, with or without regional lymph nodes RT. B was administrated as an equivalent of 5 mg/kg every week for 1 year. The safety profile (using the Common Terminology Criteria for Adverse Events version 3.0) was evaluated at 1, 3 and 5 years after the completion of radiotherapy. Results: From October 2007 to January 2012, 151 patients totally included. Median follow-up was 60 months (36-84) and 5 years late toxicities were available for 104 patients (46 with B and RT, 58 with RT alone). Median age was 51 (22-81). 61% of patients received regional lymph nodes RT. The majority of tumor was triple negative (65.6%), tumor size &amp;lt;2cm (50%) and nodal status negative (63.8%). Median total dose of B was 15000 mg (13200 – 18550) and median duration was 11.2 months (11-12.6). No grade ≥3 toxicity was observed. Only 16 patients had grade 1-2 toxicities (8 treated with B and RT, 8 with RT alone): n=4 (3.8%) had grade 1 pain, n=5 (4.8%) had grade 1-2 fibrosis, n=1 (1%) had grade 2 telangiectasia and n=5 (4.8%) had grade 1-2 lymphoedema. No significant difference between the 2 arms was observed. One patient of 46 evaluated had Left Ventricular Ejection Fraction inferior to 50%. At 5 years, overall survival was 93.8%, disease free-survival 89% and locoregional free-survival 93.1 %. Conclusion: Concurrent B and locoregional RT provides acceptable 5-years toxicities in patients with non-metastatic breast cancer. No grade ≥3 toxicity was observed. Citation Format: Clément-Zhao A, Tanguy M-L, Cottu P, De La Lande B, Bontemps P, Lemanski C, Baumann P, Levy C, Peignaux K, Reynaud-Bougnoux A, Gobillion A, Kirova Y. TOxicities of Locoregional Radiotherapy Associated with Bevacizumab in patients with non-metastatic breast cancer (TOLERAB): Final long-term evaluation [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P3-12-06.

Factors Associated With Fatigue in Patients with Breast Cancer Undergoing External Beam Radiation Therapy

A Prospective Single-Arm Study of Daily Online Adaptive Radiation Therapy for Cervical Cancer with Reduced Planning Target Volume Margin: Acute Toxicity and Dosimetric Outcomes.

MD, FRCS, FRCRMeyerstein Institute of Oncology and Academic Department of Surgery, University College London Hospitals NHS Trust,London, UKIn Time magazine’s extensively researched breast cancerissue (June 10, 2002), one particular quote had a specialresonance for us. In the introduction to a remarkablycomprehensive article, Dr Julie Gralow, an Oncologist atthe Fred Hutchinson Cancer Research Centre in Seattle,stated ‘‘We may be far overtreating our patients… We’venow got women being diagnosed with tumours that wouldprobably never have been treated if we didn’t havemammography. They probably would have lived long,natural, healthy lives never knowing they had breastcancer’’ (J Gralow, quoted in [1]).For some years it has been apparent that, for manypatients, powerful treatment by surgery (even when limitedto tumour excision with breast preservation) together witha 6 week programme of radiation therapy may be morethan sufficient. We already know a good deal (althoughnot of course enough) about the profile of a typical breastcancer patient with low risk of local and distant recur-rence: a small, low or moderate grade tumour, surgicallycompletely excised, positive for oestrogen and/or proges-terone receptors, negative for HER2 and with negativeaxillary nodes. Post-menopausal patients clearly have alower incidence of local recurrence; for example, in thelarge study by Bartelink et al [2], patients over the age of60 years had a rate of local recurrence following 50 Gywhole breast radiation of only 4% (without an additionalboost), the rate reducing still further to 2.5% with anadditional 16 Gy given by electron beam therapy. Forpatients aged 41 to 50 years, the rates were 9.5% and 5.8%,respectively (median follow-up 5.1 years). What’s more, anever increasing number of patients now present with smalltumours (,1 cm) identified on mammographic screening,of whom approximately three-quarters will have oestrogenreceptor (ER)/progesterone receptor (PR) positive tumours,for which targeted hormone therapy with tamoxifen offerssustained long-term benefit for both local and distantrelapse [3, 4]. Using a well tolerated oral aromataseinhibitor such as Anastrazole reduces the risk still further(for both local and distant relapse), also, incidentally,reducing by three-quarters the risk of development of acontralateral primary breast cancer [5].For all these reasons, we strongly support Gralow’sview. Even in younger women known to be at higher riskof relapse, including those with axillary node-positivedisease, the use of systemic adjuvant cytotoxics sharplyreduces the risk of recurrence [3, 4, 6]. For hormonereceptor-positive patients, i.e. the large majority, adjuvanthormone therapy as well as surgical or medical oophor-ectomy all add further benefit [2–4, 6].What is the consequence of Gralow’s observation? Inthe past, it has been regarded as mere flight of fancy toimagine that we can identify patients at such low risk ofrecurrence that a less intensive form of treatment thanlocal surgical excision followed by whole breast irradiationcould be regarded as ‘‘adequate’’. In this sense, thisgeneral policy remains little different in principle from theequally compelling (in its day) policy of radical, then lessdamaging forms of mastectomy – although admittedly,using local excision, breast preservation and post-operativeradiotherapy is generally regarded as more ‘‘humane’’ eventhough attempts at demonstrating an improved quality oflife have been largely elusive [7]. None the less, theevolving history of local treatment for early breast cancerhas centred on an ever increasing recognition of theimportance of breast conservation for body image andcosmesis, an essential requirement for most women. Thishas largely been achieved by the increasing acceptance ofbreast-conserving surgery with post-operative radiotherapy[8]. Yet despite this ready acceptance, recent data from theworld’s largest ever randomized breast cancer study, withexcellent quality control and a high level of expertise,confirm a mastectomy rate approaching 50% [ATACTrialists Group, unpublished data].We believe that the time has come to move on further.For many patients, particularly those presenting over theage of 50 years with small, low grade, ER positive, axillarynode negative tumours, it is surely right to question thenecessity of a lengthy and sometimes damaging course ofradiation therapy. Radiation oncologists who are totallysatisfied with their often excellent cosmetic results and lowrelapse rates following standard treatment should bearin mind the work of the Oxford-based Early BreastCancer Trialists’ Collaborative Group, namely that despitea lower breast cancer cause-specific death rate in irradiatedpatients, the increased mortality for other non-cancercauses wipes out this advantage [9]. The assumption thatthe excess non-cancer-related deaths in this large meta-analysis were due essentially to reliance on older outmodedradiation techniques may be correct – but it remains anassumption only, and considerable additional data attestto the cardiac, pulmonary and neurological dangers ofwhole breast irradiation [10–12]. Moreover, the use ofanthracycline-based chemotherapy regimens apparentlyincreases some of these risks still further [13].

Moderately hypofractionated radiation therapy for breast cancer: A Brazilian cohort study

Outcomes of postoperative radiation therapy for breast cancer in older women according to age and comorbidity status: An observational retrospective study in 752 patients.

Purpose/Objectives Few data are available regarding the safety of the concurrent combination of bevacizumab with adjuvant radiotherapy (RT) in breast cancer, especially in terms of late toxicity. The aim of this study was to determine early and late loco-regional toxicities among patients with non-metastatic breast cancer treated with this combination. Materials/Methods In our prospective and descriptive study, we analyzed loco-regional toxicities of adjuvant RT in patients with non-metastatic breast cancer receiving either concurrent bevacizumab or not in the randomized trial BEATRICE. Early and late toxicities were assessed by the Common Terminology Criteria for Adverse Events (v3.0). Evaluation was done during RT and 12 months after the end of RT. All patients provided written informed consent before enrollment. Statistical analysis was performed to analyze toxicity between the two groups. Results From September 2007 to July 2009, we included 84 patients from the randomized trial BEATRICE which evaluate the efficacy and safety of the addition of bevacizumab to standard adjuvant therapy in patients with triple negative breast cancer; 39 women received an adjuvant RT with concurrent bevacizumab and 45 women received an adjuvant RT alone. Evaluation at 12 months was available for all the patients. All patients had a triple negative non-metastatic breast cancer and had an adjuvant chemotherapy then RT. Among patients receiving concurrent bevacizumab with RT, a total of 35 patients (90%) achieved a whole breast irradiation (median dose: 50 Gy) with a boost in the surgical bed (median dose: 16 Gy) and 4 patients (10%) had a post mastectomy RT (median dose 50 Gy); lymph node RT was performed in 19 patients (49%) with internal mammary chain RT in 12 patients (31%). Mean time of bevacizumab treatment was 11.7 months [2.1-12.6] and mean total dose of bevacizumab was 15000 mg [3330-28080]. Among patients receiving RT alone, 38 patients (84%) achieved a whole breast irradiation (median dose: 50 Gy) with a boost in the surgical bed (median dose: 16 Gy) and 7 patients (16%) had a post mastectomy RT (median dose 50 Gy); lymph node RT was performed in 21 patients (47%) with internal mammary chain RT in 14 patients (31%). Radiation treatment parameters were not significantly different between the two groups. Incidence of acute grade 3 dermatitis was 10% in patients receiving bevacizumab associated with RT and 6% in patients receiving RT alone without significant difference. One year after the end of RT, the most common late toxicities in the group receiving bevacizumab and RT were grade 1-2 pain (18%), grade 1-2 fibrosis (8%), grade 1-2 arm lymphedema (8%) and grade 1-2 telangiectasia (6%).There was no significant difference in pain, radiation fibrosis, telangiectasia, arm lymphedema and dyspnea between the two groups. No patient experienced grade 3-4 toxicity in the two groups. Conclusions Our results indicate that concurrent bevacizumab with loco-regional RT provide acceptable early and late toxicities after one year in patients with non-metastatic breast cancer. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P5-14-11.

Initial Experience With 3-dimensional Topographic Applicator Brachytherapy for Treatment of Nonmelanoma Skin Cancers on the Nose and Ear