Ribociclib plus letrozole in male patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer: subgroup analysis of the phase IIIb CompLEEment-1 trial.

PURPOSE: CompLEEment-1 (NCT02941926) is a single-arm, open-label, multicentre phase IIIb study investigating the safety and efficacy of ribociclib plus letrozole (RIB + LET) in a large, diverse cohort who have not received prior endocrine therapy (ET) for advanced disease. We present an exploratory analysis of male patients. METHODS: Eligible patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC), who had no prior ET and ≤ 1 line of prior chemotherapy for advanced disease, received RIB + LET. Male patients also received goserelin or leuprolide. Primary endpoint was safety and tolerability; efficacy was a secondary endpoint. RESULTS: In total, 39/3246 patients were male. Baseline characteristics were similar to the overall population. Male patients experienced fewer treatment-related adverse events (AEs) and treatment-related serious AEs compared with the overall population; fewer male patients had treatment-related AEs leading to discontinuation, adjustment/interruption, or additional therapy. One male patient died as a result of a serious AE that was not considered to be treatment-related. The most common AE was neutropenia; the incidence of grade ≥ 3 neutropenia in males (41.0%) was lower than in the overall population (57.2%). Median follow-up was 25.4 months; median time to progression was not reached in males versus 27.1 months for the overall population. CONCLUSION: The clinical benefit and overall response rates in males were consistent with the overall population. This analysis demonstrates the safety and efficacy of ribociclib in a close-to-real-world setting, supporting the use of RIB + LET in male patients with HR+, HER2- ABC. TRIAL REGISTRATION NUMBER: NCT02941926 (Registered 2016).

Design and Development of a Medical Image Databank for Assisting Studies in Radiomics.

CompreHensive Digital ArchiVe of Cancer Imaging - Radiation Oncology (CHAVI-RO) is a multi-tier WEB-based medical image databank. It supports archiving de-identified radiological and clinical datasets in a relational database. A semantic relational database model is designed to accommodate imaging and treatment data of cancer patients. It aims to provide key datasets to investigate and model the use of radiological imaging data in response to radiation. This domain of research area addresses the modeling and analysis of complete treatment data of oncology patient. A DICOM viewer is integrated for reviewing the uploaded de-identified DICOM dataset. In a prototype system we carried out a pilot study with cancer data of four diseased sites, namely breast, head and neck, brain, and lung cancers. The representative dataset is used to estimate the data size of the patient. A role-based access control module is integrated with the image databank to restrict the user access limit. We also perform different types of load tests to analyze and quantify the performance of the CHAVI databank.

Full population results from the core phase of CompLEEment-1, a phase 3b study of ribociclib plus letrozole as first-line therapy for advanced breast cancer in an expanded population.

PURPOSE: CompLEEment-1 is a phase 3b trial in an expanded patient population with hormone receptor-positive (HR +), human epidermal growth factor receptor-2-negative (HER2-) advanced breast cancer (ABC), the largest current trial of cyclin-dependent kinase 4 and 6 inhibitors in ABC. METHODS: Patients treated with ≤ 1 line of prior chemotherapy and no prior endocrine therapy for ABC received ribociclib 600 mg/day (3-weeks-on/1-week-off) plus letrozole 2.5 mg/day and additionally monthly goserelin/leuprolide in men and pre-/perimenopausal women. Eligibility criteria allowed inclusion of patients with stable CNS metastases and an Eastern Cooperative Oncology Group performance status of 2. Primary objectives were safety and tolerability, and secondary objectives were efficacy and quality of life (QoL). RESULTS: Overall, 3,246 patients were evaluated (median follow-up 25.4 months). Rates of all-grade and grade ≥ 3 treatment-related adverse events (AEs) were 95.2% and 67.5%, respectively. Treatment-related discontinuations due to all grade and grade ≥ 3 AEs occurred in 12.9% and 7.3% of patients, respectively. Rates of all-grade AEs of special interest (AESI) were as follows: neutropenia (74.5%), increased alanine aminotransferase (16.2%), increased aspartate aminotransferase (14.1%), and QTcF prolongation (6.7%); corresponding values for grade ≥ 3 AESI were 57.2%, 7.7%, 5.7%, and 1.0%, respectively. Median time to progression was 27.1 months (95% confidence interval, 25.7 to not reached). Patient QoL was maintained during treatment. CONCLUSION: Safety and efficacy data in this expanded population were consistent with the MONALEESA-2 and MONALEESA-7 trials and support the use of ribociclib plus letrozole in the first-line setting for patients with HR + , HER2- ABC. TRIAL REGISTRATION: linicalTrials.gov NCT02941926.

AutoIHC-Analyzer: computer-assisted microscopy for automated membrane extraction/scoring in HER2 molecular markers.

Human epidermal growth factor receptor 2 (HER2) is one of the widely used Immunohistochemical (IHC) markers for prognostic evaluation amongst the patient of breast cancer. Accurate quantification of cell membrane is essential for HER2 scoring in therapeutic decision making. In modern laboratory practice, expert pathologist visually assesses the HER2-stained tissue sample under the bright field microscope for cell membrane assessment. This manual assessment is time consuming, tedious and quite often results in interobserver variability. Further, the burden of increasing number of patients is a challenge for the pathologists. To address these challenges, there is an urgent need with a rapid HER2 cell membrane extraction method. The proposed study aims at developing an automated IHC scoring system, termed as AutoIHC-Analyzer, for automated cell membrane extraction followed by HER2 molecular expression assessment from stained tissue images. A series of image processing approaches have been used to automatically extract the stained cells and membrane region, followed by automatic assessment of complete and broken membrane. Finally, a set of features are used to automatically classify the tissue under observation for the quantitative scoring as 0/1+, 2+ and 3+. In a set of surgically extracted cases of HER2-stained tissues, obtained from collaborative hospital for the testing and validation of the proposed approach AutoIHC-Analyzer and publicly available open source ImmunoMembrane software are compared for 90 set of randomly acquired images with the scores by expert pathologist where significant correlation is observed [(r = 0.9448; p < 0.001) and (r = 0.8521; p < 0.001)] respectively. The output shows promising quantification in automated scoring. LAY DESCRIPTION: In cancer prognosis amongst the patient of breast cancer, human epidermal growth factor receptor 2 (HER2) is used as Immunohistochemical (IHC) biomarker. The correct assessment of HER2 leads to the therapeutic decision making. In regular practice, the stained tissue sample is observed under a bright microscope and the expert pathologists score the sample as negative (0/1+), equivocal (2+) and positive (3+) case. The scoring is based on the standard guidelines relating the complete and broken cell membrane as well as intensity of staining in the membrane boundary. Such evaluation is time consuming, tedious and quite often results in interobserver variability. To assist in rapid HER2 cell membrane assessment, the proposed study aims at developing an automated IHC scoring system, termed as AutoIHC-Analyzer, for automated cell membrane extraction followed by HER2 molecular expression assessment from stained tissue images. The input image is preprocessed using modified white patch and CMYK and RGB colour space were used in extracting the haematoxylin (negatively stained cells) and diaminobenzidine (DAB) stain observed in the tumour cell membrane. Segmentation and postprocessing are applied to create the masks for each of the stain channels. The membrane mask is then quantified as complete or broken using skeletonisation and morphological operations. Six set of features were assessed for the classification from a set of 180 training images. These features are: complete to broken membrane ratio, amount of stain using area of Blue and Saturation channels to the image size, DAB to haematoxylin ratio from segmented masks and average R, G and B from five largest blobs in segmented DAB-masked image. These features are then used in training the SVM classifier with Gaussian kernel using 5-fold cross-validation. The accuracy in the training sample is found to be 88.3%. The model is then used for 90 set of unknown test sample images and the final labelling of stained cells and HER2 scores (as 0/1+, 2+ and 3+) are compared with the ground truth, that is expert pathologists' score from the collaborative hospital. The test sample images were also fed to ImmunoMembrane software for a comparative assessment. The results from the proposed AutoIHC-Analyzer and ImmunoMembrane software were compared with the expert pathologists' score where significant agreement using Pearson's correlation coefficient [(r = 0.9448; p < 0.001) and (r = 0.8521; p < 0.001) respectively] is observed. The results from AutoIHC-Analyzer show promising quantitative assessment of HER2 scoring.

Adjuvant radiation therapy in breast cancer: Recent advances & Indian data.

Breast cancer is the most common cancer among women in India, and adjuvant radiotherapy is an integral part of curative treatment in most patients. The recent decades have witnessed several advances in radiation therapy delivery. Several advances in radiation oncology have been identified which include technological advances, change in fractionation used, use of cardiac-sparing radiotherapy as well as efforts to personalize radiotherapy using accelerated partial breast irradiation or avoidance of radiotherapy in certain subpopulations. Indian data are available in most areas which have been summarized. However, increasing emphasis on research in these areas is needed so that effectiveness and safety in our setting can be established. Advances in breast cancer radiotherapy have resulted in improved outcomes. Data published from India suggest that these improved outcomes can be replicated in patients when appropriate treatment protocols are followed.

Consensus on contentious issues relevant for breast cancer management for the Indian scenario: Statements following a multicentre expert group meeting.

Management of breast cancer is multidisciplinary requiring critical analysis of emerging evidence especially with its appropriateness to local practice. A high level expert committee meeting was held to arrive at a consensus on controversial practical breast cancer management policies for Indian patients. Indian experts (n=39) from government and private centres who were part of the breast cancer multidisciplinary group, participated in the consensus meeting. A set of controversial yet practical questions were circulated among the experts at least two weeks in advance of the consensus meeting. International experts from the UK (n=6) also participated in the scientific discussions to add further light on the topics. The experts voted on the practical acceptable management policy for India. Consensus was defined as overwhelming (90-100% concurrence in voting), moderate (70-89% concurrence), low (50-70% concurrence) and non-consensus (<50% concurrence). Fifty eight questions based on pragmatic management strategies were framed and circulated to 39 participants. An overwhelming consensus was received in 51 of the 58 questions. The group considered the available evidence with a view for its practical applicability in Indian patients. This consensus document may aid in shaping breast cancer care for the breast oncology practitioners as well as the policymakers in the country.

Research Goal-Driven Data Model and Harmonization for De-Identifying Patient Data in Radiomics.

There are various efforts in de-identifying patient's radiation oncology data for their uses in the advancement of research in medicine. Though the task of de-identification needs to be defined in the context of research goals and objectives, existing systems lack the flexibility of modeling data and normalization of names of attributes for accomplishing them. In this work, we describe a de-identification process of radiation and clinical oncology data, which is guided by a data model and a schema of dynamically capturing domain ontology and normalization of terminologies, defined in tune with the research goals in this area. The radiological images are obtained in DICOM format. It consists of diagnostic, radiation therapy (RT) treatment planning, RT verification, and RT response images. During the DICOM de-identification, a few crucial pieces of information are taken about the dataset. The proposed model is generic in organizing information modeling in sync with the de-identification of a patient's clinical information. The treatment and clinical data are provided in the comma-separated values (CSV) format, which follows a predefined data structure. The de-identified data is harmonized throughout the entire process. We have presented four specific case studies on four different types of cancers, namely glioblastoma multiforme, head-neck, breast, and lung. We also present experimental validation on a few patients' data in these four areas. A few aspects are taken care of during de-identification, such as preservation of longitudinal date changes (LDC), incremental de-identification, referential data integrity between the clinical and image data, de-identified data harmonization, and transformation of the data to an underlined database schema.

Redefining adequate margins in oral squamous cell carcinoma: outcomes from close and positive margins.

PURPOSE: Adequacy of surgical margins impacts outcomes in oral cancer. We sought to determine whether close and positive margins have different outcomes in patients with oral cancer. METHODS: Retrospective data from 612 patients with oral carcinoma were analyzed for the effect of margin status on locoregional recurrence-free survival (LRFS), disease-free survival (DFS) and overall survival (OS). RESULTS: A total of 90 cases (14.7%) had close margins and 26 patients (4.2%) had positive margins. Recurrences were documented in 173 patients (28%), of which 137 (22% of the study sample) were locoregional, and 164 patients (27%) had died. Among patients with close or positive margins, a cutoff of 1 mm optimally separated LRFS (adjusted p = 0.0190) and OS curves (adjusted p = 0.0168) whereas a cutoff of 2 mm was sufficient to significantly separate DFS curves (adjusted p = 0.0281). CONCLUSIONS: Patients with oral carcinoma with positive margins (< 1 mm) had poorer outcomes compared to those with close margins (1-5 mm) in terms of LRFS, DFS and OS. There is a suggestion that a cutoff of < 2 mm might provide slightly more separation for DFS.

De-Identification of Radiomics Data Retaining Longitudinal Temporal Information.

We propose a de-identification system which runs in a standalone mode. The system takes care of the de-identification of radiation oncology patient's clinical and annotated imaging data including RTSTRUCT, RTPLAN, and RTDOSE. The clinical data consists of diagnosis, stages, outcome, and treatment information of the patient. The imaging data could be the diagnostic, therapy planning, and verification images. Archival of the longitudinal radiation oncology verification images like cone beam CT scans along with the initial imaging and clinical data are preserved in the process. During the de-identification, the system keeps the reference of original data identity in encrypted form. These could be useful for the re-identification if necessary.

Near-set Based Mucin Segmentation in Histopathology Images for Detecting Mucinous Carcinoma.

This paper introducesnear-set based segmentation method for extraction and quantification of mucin regions for detecting mucinouscarcinoma (MC which is a sub type of Invasive ductal carcinoma (IDC)). From histology point of view, the presence of mucin is one of the indicators for detection of this carcinoma. In order to detect MC, the proposed method majorly includes pre-processing by colour correction, colour transformation followed by near-set based segmentation and post-processing for delineating only mucin regions from the histological images at 40×. The segmentation step works in two phases such as Learn and Run.In pre-processing step, white balance method is used for colour correction of microscopic images (RGB format). These images are transformed into HSI (Hue, Saturation, and Intensity) colour space and H-plane is extracted in order to get better visual separation of the different histological regions (background, mucin and tissue regions). Thereafter, histogram in H-plane is optimally partitioned to find set representation for each of the regions. In Learn phase, features of typical mucin pixel and unlabeled pixels are learnt in terms of coverage of observed sets in the sample space surrounding the pixel under consideration. On the other hand, in Run phase the unlabeled pixels are clustered as mucin and non-mucin based on its indiscernibilty with ideal mucin, i.e. their feature values differ within a tolerance limit. This experiment is performed for grade-I and grade-II of MC and hence percentage of average segmentation accuracy is achieved within confidence interval of [97.36 97.70] for extracting mucin areas. In addition, computation of percentage of mucin present in a histological image is provided for understanding the alteration of such diagnostic indicator in MC detection.

Challenges in the Assessment of Medullary Bone Invasion in Oral Cavity Cancers and Its Prognostic Significance.

BACKGROUND: As per AJCC 8th edition TNM staging system, bone invasion is a poor prognostic marker that upstages oral cavity squamous carcinoma (OSCC) to pT4a. Cortical erosion alone of bone or tooth socket by a gingival primary is not sufficient to upstage a tumour. The differentiation of cortical erosion from invasion through the cortical bone into the medulla is often challenging, limiting accurate staging. This review aims to assess the difficulties in differentiating cortical erosion from medullary invasion and evaluate the prognostic significance of different patterns of bone involvement. METHODS: A retrospective review of OSCC with primary curative surgery and bone resection treated at a single-center over 10 years, was performed to assess the prognostic significance of bone invasion. Hematoxylin-eosin stained slides of a subset of cases were re-reviewed in a planned manner to assess difficulties in precise categorization (no invasion/erosion/cortical invasion and medullary invasion), evaluate interobserver agreement, and correlate with clinical outcome. RESULTS: Five hundred and ninety patients were included, with a median follow-up of 28 months. On univariate analysis, the 3-year local, nodal and distant metastasis control were not significantly different in the 3 groups of no invasion, erosion, and invasion (p = 0.43, 0.47, and 0.47, respectively). Overall survival (OS) at 3 years was 78.1% and disease-free-survival(DFS) was 63.7% in the entire cohort. On univariate analysis, there was significant difference in OS and DFS based on these groups. This did not translate into independent prognostic benefit on multivariable analysis (p = 0.75 and 0.19, respectively). The independent prognostic factors were margin positivity, tumor differentiation, perineural invasion and pathological nodal involvement. Planned re-review of a subset of 202 cases resulted in a change in bone involvement category in 26/202 cases, which was mainly due to difficulty in assessing cortico-medullary junction near the tooth socket and bone fragmentation. The assessment showed moderate to near complete agreement (kappa 0.59-0.82) between 2 observers. CONCLUSION: Our study shows that bone involvement is not an independent prognostic marker and there is no specific correlation of medullary invasion with outcome over those that showed cortical erosion. Several factors contribute to difficulties and interobserver variability in assessing bone involvement.

Are oral cancers effectively palliated with radiotherapy? Outcomes of treatment with a modified QUAD SHOT regimen.

BACKGROUND: This study assessed a palliative radiotherapy regimen using daily radiation over 4 days for three courses in inoperable head and neck cancers, emphasizing oral primary cancers. METHODS: Retrospective data of 116 patients treated with a daily dose of 3.6-3.7 Gy in four fractions over 4 days to a total of three courses, with a 2-week gap after every course, were analyzed for survival outcomes. A subgroup analysis was done for oral cancer. RESULTS: Ninety-nine (85%) completed three courses. Overall subjective response rate was 77%. Median overall survival and progression-free survival were 12 months (95% confidence interval [CI]: 8-20) and 8 months (95% CI: 6-10), with numerically higher overall survival in oral cancer. The treatment was well tolerated, with no on-treatment hospitalization or grade 3-4 toxicities. CONCLUSION: The modified QUAD SHOT regimen is practical for palliation in head and neck cancers.

Enhancing quality assurance in radiotherapy for gynaecological cancers: implementation of an on-demand peer review process.

OBJECTIVES: Ensuring high-quality radiotherapy requires peer-reviewing target volumes. The Royal College of Radiologists recommends peer review specifically for individual target volumes in cases of gynaecological cancers. This study presents the outcomes of implementing an on-demand peer review system for gynaecological cancers within our institute. METHODS: The peer review process was planned for gynaecological cancer cases intended for curative radiotherapy. After junior clinical oncologists (COs) completed the segmentation, two senior COs specializing in gynaecological cancers conducted the peer review. All peer review outcomes were recorded prospectively. The audit process compliance, the proportion of patients requiring major and minor modifications in target volumes, the direction of changes, and the factors influencing these changes were reported. RESULTS: A total of 230 patients were eligible, and out of these, 204 (88.3%) patients underwent at least one peer review. Among the patients, 108 required major modifications in their target volumes. P-charts revealed a stabilization in the need for major modifications at the end of three months, indicating that 38.2% and 28% of patients still required major modifications for the nodal and primary CTV, respectively. Multivariable analysis demonstrated that major modifications were associated with the use of extended field radiotherapy and radical radiation in non-cervical primary cases. CONCLUSIONS: An on-demand peer review system was feasible and resulted in clinically meaningful, major modifications in the target volumes for 53% of patients. ADVANCES IN KNOWLEDGE: Gynaecological cancers require ongoing peer review to ensure quality of care in radiotherapy. A flexible on-demand system not only ensures that patient treatment start is not delayed but also has an important educational role for junior trainees.

18F-fluorodeoxyglucose PET-CT-guided pelvic chemoradiation therapy using helical tomotherapy for locally advanced carcinoma cervix without para-aortic nodal disease: Clinical and patient-reported outcomes from a prospective phase 2 study.

INTRODUCTION: Locally advanced carcinoma cervix (LACC) is a heterogeneous disease with variable combinations of primary tumour extensions with or without nodal involvement. Metabolic information from 18 fluro-deoxyglucose positron emission tomography combined with contrast-enhanced computerized tomography (FDG PET-CT) may potentially augment treatment decision-making for LACC. This study ascertained FDG-PET CT influence on chemoradiation therapy (CTRT) decisions in LACC. We report oncologic and patient-reported outcome measures (PROMs). METHODS: FDG PET-CT scans were reviewed independently by two nuclear medicine specialists and two radiation oncologists. Pelvic CTRT plan digressions were documented and therapy was adapted accordingly. Pelvis radiation (50 Gy/25#/5 weeks) using tomotherapy with weekly cisplatin was used in node-negative disease. Dose-escalated simultaneous integrated boost (SIB) 60 Gy/25#/5 weeks was delivered to involved pelvic nodes. All received brachytherapy. Post-treatment PET-CT scans were at 6 months. Functional assessment of cancer therapy scores were calculated at baseline, treatment completion, 3 months, 1 year and 3 years. RESULTS: Between November 2015 and January 2018, 85 patients were screened, and 77 consented. Extrapelvic disease was seen in 12 (16%) patients (9 para-aortic nodes, 2 distant metastases and 1 synchronous carcinoma breast); 60 patients were included in the final analysis. Decision changes were seen in 10/77 (13%) screened, 8/60 (13%) included and 32 (53.3%) received SIB. Post-treatment, 27 (45%) had grade 2 GI/GU/GYN toxicity, one (2%) had grade 3 GI and five (8.3%) had grade 3 neutropenia. At median overall survival of 54.2 months (95% CI 52.8-58.3), 5-year local failure, pelvic nodal and para-aortic nodal-free survival were 86.8% (95% CI 78.0-96.6), 85.2% (95% CI 76.1-95.3) and 85.2% (95% CI 76.2-95.4). Functional assessment of cancer therapy trial outcome index (FACT TOI) improved by 10.43 at 3 months with no further decline. Grade 3 toxicity was noted for abdominal pain in one (1.7%), cystitis in four (6.7%) and lymphoedema in one (1.7%) at 5 years. CONCLUSION: PET-CT resulted in major decision changes in 13%. PET-adapted CTRT was associated with acceptable toxicity, encouraging long-term survival and improvement in PROMS.

Protocol for the development of a core outcome set and reporting guidelines for locoregional treatment in neoadjuvant systemic breast cancer treatment trials: the PRECEDENT project.

INTRODUCTION: Neoadjuvant systemic anticancer therapy (neoSACT) is increasingly used in the treatment of early breast cancer. Response to therapy is prognostic and allows locoregional and adjuvant systemic treatments to be tailored to minimise morbidity and optimise oncological outcomes and quality of life. Accurate information about locoregional treatments following neoSACT is vital to allow the translation of downstaging benefits into practice and facilitate meaningful interpretation of oncological outcomes, particularly locoregional recurrence. Reporting of locoregional treatments in neoSACT studies, however, is currently poor. The development of a core outcome set (COS) and reporting guidelines is one strategy by which this may be improved. METHODS AND ANALYSIS: A COS for reporting locoregional treatment (surgery and radiotherapy) in neoSACT trials will be developed in accordance with Core Outcome Measures in Effectiveness Trials (COMET) and Core Outcome Set-Standards for Development guidelines. Reporting guidance will be developed concurrently.The project will have three phases: (1) generation of a long list of relevant outcome domains and reporting items from a systematic review of published neoSACT studies and interviews with key stakeholders. Identified items and domains will be categorised and formatted into Delphi consensus questionnaire items. (2) At least two rounds of an international online Delphi survey in which at least 250 key stakeholders (surgeons/oncologists/radiologists/pathologists/trialists/methodologists) will score the importance of reporting each outcome. (3) A consensus meeting with key stakeholders to discuss and agree the final COS and reporting guidance. ETHICS AND DISSEMINATION: Ethical approval for the consensus process will be obtained from the Queen's University Belfast Faculty Ethics Committee. The COS/reporting guidelines will be presented at international meetings and published in peer-reviewed journals. Dissemination materials will be produced in collaboration with our steering group and patient advocates so the results can be shared widely. REGISTRATION: The study has been prospectively registered on the COMET website (https://www.comet-initiative.org/Studies/Details/2854).

Definitive chemoradiation for oropharyngeal squamous carcinomas: Outcomes with intensity-modulated radiation therapy using simultaneous integrated boost, in a majorly p16 negative cohort.

BACKGROUND: The literature on modern-era outcomes of oropharyngeal squamous carcinoma (OPSCC) in India is limited. MATERIALS AND METHODS: We analyzed records of consecutive patients with OPSCC treated using a curative SIB IMRT regimen of 66 Gy/30#/6 weeks. RESULTS: One hundred fifteen patients from July 2011 to December 2018 were analyzed. Twenty of 69 patients tested positive for p16. In p16 positive patients, the K-M probability of being disease free and alive at 2 years, with at least one follow-up 3 months after treatment, was 83% (median not reached) compared with 48% if p16 was unknown/negative. Patients staged as IVB p16 negative had a 2-year DFS of 25%. Patients unfit for cisplatin and consequently received other agents had 2-year DFS estimated at 20%. CONCLUSIONS: Intensity-modulated radiation therapy (IMRT) with simultaneous integrated boost (SIB) and concurrent chemotherapy was feasible, with toxicity and disease control comparable to available literature. AJCC Stage IVB p16 negative disease had notably poor outcome.

Oncologic safety of breast conservation following NACT in women with locally advanced breast cancer.

Introduction: Breast conservation surgery (BCS) is the accepted standard of treatment for early breast cancer, with evidence from randomized controlled and population-based studies. The oncological outcome of BCS in locally advanced breast cancer (LABC) is mainly available from retrospective series with a small sample size and a shorter follow-up duration. Methods: A retrospective observational study of 411 non-metastatic LABC patients who received neoadjuvant chemotherapy (NACT) followed by surgery from 2011 to 2016. We retrieved the data from a prospectively maintained database and electronic medical records. Survival data were analyzed by Kaplan-Meier curves and Cox regression using Statistical Package for the Social Sciences 25 and STATA 14. Results: 146/411 (35.5%) women had BCS with a margin positivity rate of 3.42%. With a median follow-up of 64 months (IQR 61, 66), the local relapse rate was 8.9% in BCS and 8.3% after mastectomy. The estimated 5-year locoregional recurrence-free survival (LRFS), recurrence-free survival (RFS), distant disease-free survival (DDFS) and overall survival (OS) rates of BCS were 86.9%, 63.9%, 71% and 79.3%, and 90.1%, 57.9%, 58.3% and 71.5% in the mastectomy group. On univariate analysis, BCS showed superior survival outcomes compared to mastectomy (unadjusted HR (95% CI) for RFS: 0.70 (0.50-1), DDFS: 0.57 (0.39-0.84), OS: 0.58 (0.36-0.93)). After adjusting for age, cT stage, cN stage, poorer chemotherapy response (ypT0/is, N0) and radiotherapy, BCS and mastectomy groups were found comparable in terms of LRFS (HR: 1.1, 0.53-2.3), DDFS (HR: 0.67, 0.45-1.01), RFS (HR: 0.80, 0.55-1.17) and OS (HR: 0.69, 0.41-1.14). Conclusion: BCS is technically feasible in LABC patients. LABC patients who respond well to NACT can be offered BCS without compromising survival outcomes.