Search

Parotid sparing adaptive radiotherapy (PSART) is resource intensive to implement. Selection criteria for using ART and its impact on quality of life (QoL) is poorly reported. This has been addressed in our study.Patients planned for curative radiotherapy for Head Neck Cancers were recruited following informed consent in a prospective cohort study. PSART was planned if the mean dose to index parotid(s) increased by 2% from the baseline approved plan. To assess the resource requirements of PSART manpower and time required for treatment planning both for initial as well as PSART was documented. Patient reported QoL using QualiXeQLS and EORTC QLQ C30 and HN35 were obtained pre radiotherapy, and at 3 and 9 months post radiotherapy.Of the ninety patients accrued, 87 were evaluable. 45 (51%) received PSART based on the prespecified criteria. The average time spent in contouring (276 min versus 133 min) and treatment planning (293 min versus 108 min) were almost doubled when PSART was implemented. XeQoL scores at 3 months were significantly worse in those receiving PSART (mean 2.3 vs 1.2, p 0.002). Despite this, xerostomia related QoL recovered to near baseline scores by 9 months after receiving PSART.Implementation of PSART is resource intensive. The proposed cutoff for implementing PSART identifies a higher risk population that have worse xerostomia related quality of life. This study lays the foundation for a randomized trial to determine the efficacy of PSART on xerostomia related QoL.

PURPOSE A COVID-19 lockdown in India posed significant challenges to the continuation of radiotherapy (RT) and systemic therapy services. Although several COVID-19 service guidelines have been promulgated, implementation data are yet unavailable. We performed a comprehensive audit of the implementation of services in a clinical oncology department. METHODS A departmental protocol of priority-based treatment guidance was developed, and a departmental staff rotation policy was implemented. Data were collected for the period of lockdown on outpatient visits, starting, and delivery of RT and systemic therapy. Adherence to protocol was audited, and factors affecting change from pre-COVID standards analyzed by multivariate logistic regression. RESULTS Outpatient consults dropped by 58%. Planned RT starts were implemented in 90%, 100%, 92%, 90%, and 75% of priority level 1-5 patients. Although 17% had a deferred start, the median time to start of adjuvant RT and overall treatment times were maintained. Concurrent chemotherapy was administered in 89% of those eligible. Systemic therapy was administered to 84.5% of planned patients. However, 33% and 57% of curative and palliative patients had modifications in cycle duration or deferrals. The patient’s inability to come was the most common reason for RT or ST deviation. Factors independently associated with a change from pre-COVID practice was priority-level allocation for RT and age and palliative intent for systemic therapy. CONCLUSION Despite significant access limitations, a planned priority-based system of delivery of treatment could be implemented.

PURPOSE There are limited reports of quality metrics in glioblastoma. We audited our adherence to quality indicators as proposed in the PRIME Quality Improvement study. METHODS This is a retrospective audit of patients treated between 2017 and 2020. After postsurgical integrated diagnosis, patients received radiotherapy (RT) with concurrent and adjuvant temozolomide (TMZ). Multiparametric magnetic resonance imaging at predefined times guided management. Numbers with proportions for indices were calculated. Survival was estimated using the Kaplan-Meier method. RESULTS One hundred six patients were consecutively treated. The median age was 55 years (interquartile range of 47-61 years) with a male preponderance (68%). Ninety-six (90.6%) patients underwent subtotal resection, and 10 (9.4%) biopsy alone. Isocitrate dehydrogenase was wild-type in 96 (91%), and O6-methylguanine-DNA methyltransferase was unmethylated in 70 (66.0%) patients. Telomerase reverse transcriptase promoter was mutated in 64 (60.4%), and TP53 was mutated in 22 (20.8%). Concurrent radiation and TMZ were planned for 104 (98.1%), and radiation alone for 2 (1.9%). The median time to concurrent RT-TMZ was 36 days (interquartile range 30-44 days). All patients planned for RT-TMZ completed treatment, but only 81 (76%) completed adjuvant TMZ. Sixty-three (59%) completed six cycles, 18 (17%) received less than six cycles, and 25 (24%) did not receive adjuvant TMZ. At a median follow-up of 24 months (range 21-31 months), the median (95% CI) progression-free survival and overall survival were 11 (95% CI, 9.4 to 13.0) and 20.0 (95% CI, 15 to 26) months, respectively. CONCLUSION Our patients met quality indices in most domains; outcomes are comparable with global results. Metrics will be periodically evaluated to include new standards and assess continuous service appropriateness.

HYPORT adjuvant trial is a randomised phase III open-label noninferiority trial comparing standard moderately hypofractionated 3 week adjuvant radiation therapy in breast cancer with a novel 1-week schedule. The trial was initiated in March 2019 and is open to recruitment with a total sample size of 2100. We report the results of dosimetric quality assurance, acute toxicity and pre planned first interim safety analysis in the first 271 patients.Stage I-III breast cancer planned for adjuvant radiation therapy to the breast/chest-wall (along with regional nodes as indicated) were randomised to receive 40 Gy/15 fractions/3 weeks or 26 Gy/5 fractions/1 week. For simultaneous integrated boost, the patients in the control arm received 8 Gy/15 fractions/3 weeks, while those in the experimental arm received 6 Gy/5 fractions/1 week (to the tumour bed). For sequential boost, the prescribed dose was 12 Gy/4 fractions/4 days in both arms. Compliance to pre specified dosimetric parameters and acute toxicities were evaluated.Data of the first 271 patients was analysed of whom 104 patients received tumour bed boost using SIB. All mandatory dosimetric criteria were met apart from one patient with a higher contralateral breast dose due to optimal internal mammary nodal coverage. Overall three patients (1.1%) experienced grade 3 radiation dermatitis (none received SIB), no other Grade 3 or higher toxicities reported.This acute toxicity interim analysis demonstrates that hypofractionated adjuvant radiotherapy with SIB for patients with breast cancer is feasible, and associated with minimal severe acute toxicities.

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.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.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.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.NCT02941926 (Registered 2016).

'No abstract'

Background Definite concurrent chemoradiation is the standard of care for locally advanced unresectable oesophageal cancers. However, heterogeneity exists in the practice of concurrent chemoradiation approaches. Here we describe the efficacy and toxicities of the standard arm of SCOPE1 protocol implemented at our institute. Methods Treatment records of 36 patients with unresectable oesophageal cancers treated with concurrent chemoradiation between January 2015 and June 2019 were audited. Treatment was based on the standard arm of SCOPE1 protocol (neoadjuvant and concurrent platinum and capecitabine with external beam radiation to a dose of 50 Gy/25 fractions/5 weeks). The electronic hospital information system and oncology information system were queried to obtain information on patient characteristics and treatment delivery patterns. Results Out of 36 patients, 35 had squamous cell carcinomas. 25% of the patients (9/36) were 70 years or older. 66.7% of patients (24/36) had T4 disease, and 16 (44.4%) had N2-N3 nodal disease at presentation. A total of 30 patients (83.3%) could not undergo surgery because of the location and locoregional extent of the disease. The median follow-up of the entire cohort and the surviving patients was 10 months (range 3-51 months) and 13 months (range 4-51 months), respectively. The median overall survival (OS) of the entire cohort was 28 months. The 2-year local progression-free survival and OS were 71.2% (95% CI: 48.5%-85.3%) and 57.4% (95%CI: 29.6%-77.6%), respectively. Commonly observed acute Grade 3 toxicities were dysphagia (22.2%) and thrombocytopenia (19.4%). Conclusion The outcomes of the SCOPE1 protocol have been validated for the first time in a different geographical, racial and ethnic population. Implementation of the standard arm of SCOPE1 protocol is feasible in our setting with acceptable adverse effects and good treatment compliance. Results are comparable to the results of the published trial.

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.

Background The Z0011 trial results have shown that axillary lymph node dissection (ALND) can be avoided in cT1-2 patients undergoing breast conservation surgery with 1–2 metastatic sentinel lymph nodes (SLNs). We compared the clinicopathological characteristics of the Z0011 eligible non-screen detected breast cancer patients’ cohort with the Z0011 trial study population. Additionally, we have explored the effect of non-sentinel metastasis on adjuvant treatment decisions and survival. Methods The details of early breast cancer (EBC) patients fulfilling Z0011 eligibility criteria were retrieved from a prospectively maintained database (2013–2017) and electronic medical records. We used Statistical Package for the Social Sciences 25 and Stata V15 for the data analysis. Results 128/194 (66%) sentinel lymph node biopsy positive patients had fulfilled the Z0011 inclusion criteria. Compared to the Z0011 study, our cohort patients were younger, with more aggressive disease (higher T2, Grade 3), had a higher rate of macrometastasis (82.8% versus 58.8%) and non-SLN metastasis (48% versus 27%). The information gained by ALND had changed decisions for chemotherapy in 3% and no change of radiotherapy in Z0011 eligible patients. Further nodal positivity in completion ALND was not significantly associated with overall survival (p = 0.86) and disease-free survival (p = 0.5). Conclusion Z0011 eligible Indian EBC patients are significantly different from the Z0011 study population, with younger age of presentation, higher grade, a higher rate of both SLN macro metastasis and non-SLN positivity. The impact of non-sentinel metastasis on adjuvant treatment decisions and survival is minimal.

Purpose Triple-negative breast cancer (TNBC) has a poor outcome compared to other subtypes, even in those with early disease. Immune checkpoint inhibitors (ICIs) have been approved in metastatic diseases and are being tested as a neoadjuvant strategy also. The response to ICIs is largely determined by the programmed death ligand 1 (PDL1) score, which also acts as a prognostic marker for outcomes. Here, we report the proportion of PDL1 expression in non-metastatic TNBC and its correlation with response to chemotherapy and outcomes. Methods We included all patients who had non-metastatic TNBC treated with neoadjuvant chemotherapy, followed by surgery with/without adjuvant radiotherapy between September 2011 and November 2017. PDL1 testing was carried out on pre-treatment tumour cells with immunohistochemistry (Ventana SP142) and was correlated with pathological response, relapse-free survival (RFS) and overall survival (OS). PDL1 staining was interpreted as negative or positive (more than 1% staining). Results A total of 107 patients were included for analysis with a median age of 47 years (28-65 yrs). The PDL1 expression of more than 1% was seen in 31 (28.97%) patients. After a median follow-up of 55 months (range: 4-93 months), median RFS and OS were not reached. PDL1 expression did not affect the achievement of pathological complete response (pCR). However, PDL1 expression improved OS (p = 0.016) and trend towards RFS (p = 0.05). Patients who achieved pCR had better RFS and OC compared to those who did not. Conclusion Our study shows PDL1 expression in 29% of the cases. PDL1 expression leads to better RFS and OS. Also, pCR improves survival.

Introduction The current study was aimed at quantifying the disparity in geographic access to cancer clinical trials in India. Methods We collated data of cancer clinical trials from the clinical trial registry of India (CTRI) and data on state-wise cancer incidence from the Global Burden of Disease Study. The total sample size for each clinical trial was divided by the trial duration to get the sample size per year. This was then divided by the number of states in which accrual was planned to get the sample size per year per state (SSY). For interventional trials investigating a therapy, the SSY was divided by the number of incident cancers in the state to get the SSY per 1,000 incident cancer cases. The SSY data was then mapped to visualise the geographical disparity.Results We identified 181 ongoing studies, of whom 132 were interventional studies. There was a substantial inter-state disparity - with a median SSY of 1.55 per 1000 incident cancer cases (range 0.00 - 296.81 per 1,000 incident cases) for therapeutic interventional studies. Disparities were starker when cancer site-wise SSY was considered. Even in the state with the highest SSY, only 29.7 % of the newly diagnosed cancer cases have an available slot in a therapeutic cancer clinical trial. Disparities in access were also apparent between academic (range: 0.21 - 226.60) and industry-sponsored trials (range: 0.17 - 70.21).Conclusion There are significant geographic disparities in access to cancer clinical trials in India. Future investigations should evaluate the reasons and mitigation approaches for such disparities.

Context: Stereotactic body radiotherapy (SBRT) is increasingly being used for early-stage lung cancer and lung oligometastases. Aims: To report our experience of setting up lung SBRT and early clinical outcomes. Settings and Design: This was a retrospective, interventional, cohort study. Subjects and Methods: Patients were identified from multidisciplinary tumor board meetings. They underwent four-dimensional computed tomography-based planning. The ROSEL trial protocol, the Radiation Therapy Oncology Group (RTOG) 0236, and the UK-Stereotactic Ablative Body Radiotherapy Consortium guidelines were used for target volume and organs-at-risks (OARs) delineation, dosimetry, and plan quality assessment. Each SBRT plan underwent patient-specific quality assurance (QA). Daily online image guidance using KVCT or MVCT was done to ensure accurate treatment delivery. Statistical Analysis Used: Microsoft Excel 2010 was used for data analysis. Results: Fifteen patients were treated to one or more lung tumors. One patient received helical tomotherapy in view of bilateral lung oligometastases at similar axial levels. All the remaining patients received volumetric modulated arc therapy (VMAT)-based treatment. The prescription dose varied from 40 to 60 Gy in 5–8 fractions with alternate-day treatment. The mean and median lung V20 was 5.24% and 5.16%, respectively (range, 1.66%–9.10%). The mean and median conformity indexes were 1.02 and 1.06, respectively (range, 0.70–1.18). After a median follow-up of 17 months, the locoregional control rate was 93.3%. Conclusions: SBRT was implemented using careful evaluation of OAR dose constraints, dosimetric accuracy and plan quality, patient-specific QA, and online image guidance for accurate treatment delivery. It was safe and effective for early-stage nonsmall cell lung cancer and lung metastases. Prospective data were collected to audit our outcomes.

Tertiary oncology center clinicians are commonly faced with the problem of managing patients with a diagnosis of breast cancer made after lumpectomy in the Primary Health Care (PHC) setting. There are no studies or guidelines that address the further surgical management in this group of patients regarding sentinel lymph node biopsy (SLNB) and need for breast post-operative cavity excision. Prospective observational study was planned to evaluate the feasibility of SLNB and defining the need for definitive breast surgery in patients diagnosed with breast cancer after lumpectomy in PHC. The study was carried out from January 2015 to August 2017 in Tata Medical Center, India, approved by institutional review board (EC/TMC/36/14). Seventy patients who underwent lumpectomy with a definitive histological analysis of breast cancer were included in this study. Each patient had definitive breast surgery and SLNB using subareoral blue dye injection followed by validation axillary dissection. The identification rate (IR) for SLNB was 92% (64/70). The median number of SLNs removed was 2 (IQR 1, 3). There were 2 patients with false negative results resulting in false negative rate (FNR) of 11%. Overall, SLNB procedure has the sensitivity of 89%, NPV of 96%, and accuracy was 97%. Peri-areoral incision of initial surgery was associated with low IR (84%) and high FNR (33%). Final histopathology showed residual invasive cancer in 43% and ductal carcinoma in situ in 14% of patients. Among 21 patients where initial lumpectomy histopathology margin was free of cancer, residual malignancy was found in 57% of patients. Prior excision of lumps for breast cancer does not affect the accuracy of SLNB. Peri-areoral scar may be associated with high FNR and low IR, although further studies are needed to validate this statement. Definitive breast surgery is required for all patients, irrespective of initial lumpectomy histopathological margin status.

Introduction Use of deep inspiration breath hold (DIBH) radiation therapy may reduce long-term cardiac mortality. The resource and time commitments associated with DIBH are impediments to its widespread adoption. We report the dosimetric benefits, workforce requirements, and potential reduction in cardiac mortality when DIBH is used for left-sided breast cancers. Methods and materials Data regarding the time consumed for planning and treating 50 patients with left-sided breast cancer with DIBH and 20 patients treated with free breathing (FB) radiation therapy were compiled prospectively for all personnel (regarding person-hours [PH]). A second plan was generated for all DIBH patients in the FB planning scan, which was then compared with the DIBH plan. Mortality reduction from use of DIBH was calculated using the years of life lost resulting from ischemic heart disease for Indians and the postulated reduction in risk of major cardiac events resulting from reduced cardiac dose. Results The median reduction in mean heart dose between the DIBH and FB plans was 166.7 cGy (interquartile range, 62.7-257.4). An extra 6.76 PH were required when implementing DIBH as compared with FB treatments. Approximately 3.57 PH were necessary per Gy of reduction in mean heart dose. The excess years of life lost from ischemic heart disease if DIBH was not done in was 0.95 per 100 patients, which translates into a saving of 12.8 hours of life saved per PH of work required for implementing DIBH. DIBH was cost effective with cost for implementation of DIBH for all left-sided breast cancers at 2.3 times the annual per capita gross domestic product. Conclusion Although routine implementation of DIBH requires significant resource commitments, it seems to be worthwhile regarding the projected reductions in cardiac mortality.

Quality Indicators for Sentinel Lymph Node Biopsy in Breast Cancer: Applicability and Clinical Relevance in a Non-screened Population: sentinel lymph node biopsy (SLNB) has replaced axillary lymph node dissection (ALND) as standard of care for management of early breast cancer. This study assessed our SLNB program against 11 published quality indicators (QIs). All breast cancer patients who underwent SLNB in our centre from June 2013–Dec 2015 were included. Clinical, pathological and follow-up data were extracted from the institutional REDCap data system. Analysis was done with SPSS 23. Following validation, 234 patients had SLNB, always performed along with primary surgery. Identification rate was 95.3% and > 1 SLN was identified in 72% of patients. SLNB positivity was 33%, of these, 100% underwent ALND. Overall 91% of QI eligible patients underwent SLNB. No ineligible patients (T4) underwent SLNB. For the patients who had radio colloid, injection criteria were met for 100%. Pathological evaluation and reporting criteria were met for 100% of patients. There were no axillary recurrences in a median follow-up of 2 years. 7.6% patients had SLN negative on frozen section but positive on final histology. 7.2% of patients with clinical negative nodes had pN2 disease in final histopathology report after surgery. Sixty percent of patients who had completion ALND had only positive SLN. This study supports the applicability of published QI of SLNB in a non-screened cohort of early breast cancer patients. Although QI were useful, modification based on patient characteristics and resource availability may be needed. These indicators can be used as audit tools to improve the overall accuracy of the procedure.

Oral squamous cell carcinoma (OSCC) diagnosis through computer vision approach is newly introduced technique in the modern diagnostic era. Mitotic cell count from related tissue histopathological images signifies the proliferative marker of cancer cell has been recognized as an essential phenomenon in diagnosis. This paper aims at developing an automated technique for accomplishing the task of mitotic cell count from related histopathological images. In this regard, a new machine learning based methodology incorporating random forest tree classifier learns over four entropy measures, fractal dimension, and seven Hu's moments based descriptors have been introduced. The performance validation summarizes that proposed methodology can detect mitotic cell efficiently from histopathological images of OSCC with 89% precision, 95% recall or sensitivity, 97.35% specificity, 96.92% accuracy, 96.45% AUC and 92% F-score measure.

Introduction: Approximately 35% of NSCLC patients in East Asia have EGFR mutations. Next-generation sequencing (NGS) provides a comprehensive mutational profile in lung cancer patients. Material and Method: Clinicopathologic characteristics and mutational profiling data was analyzed from nonsmall cell lung carcinoma /Adenocarcinoma over a duration of 42 months (October 2014 to March 2018) using next-generation sequencing Ion Ampliseq Cancer Hotspot panel v2 (Ampliseq, Life Technologies) on the Ion torrent PGM platform. Results: A total of 154 cases were processed during this period. The average number of mutations/case varied from one to four 72.07% (111/154), of these cases had minimum one genetic alteration. The most common mutated gene was TP53 gene (37.6%, n = 58) followed by EGFR (32.4%, n = 50), KRAS (18.18%, n = 28), ERBB2 (3.2%, n = 5), BRAF (1.94%, n = 3). EGFR positivity was more in females (43.3%) and non-smokers (52.08%) in comparison to males (26.7%) and smokers (16.1%). Conclusion: In this paper, we have described the comprehensive mutational profiling of a large cohort of advanced lung adenocarcinoma patients from the eastern part of India. To the best of our knowledge, this is one of the largest studies from the country describing mutations in BRAF, ERBB2, TP53 genes and their clinicopathologic/histopathologic associations in lung cancers.

Background Medical decisions made by oncology clinicians have serious implications, even when made collaboratively with the patient. Clinicians often use the Eastern Clinical Oncology Group (ECOG) performance status (PS) scores to help them make treatment-related decisions. Methods The current study explores the variability of the ECOG score when applied to 12 predetermined specially designed clinical case vignettes presented to a group of oncology clinicians (n = 72). The quantitative analysis included evaluation of variability of ECOG PS scores and exploration of rater and patient-related factors which may influence the final ECOG rating. In-depth interviews were conducted with oncology clinicians to ascertain factors that they felt were important while making treatment-related decisions. Basic and global themes were generated following qualitative data analysis. Results Quantitative results showed that there was poor agreement in ECOG rating between raters. Overall concordance with the gold standard rating ranged between 19.4% and 56.9% for the vignettes. Moreover, patients deemed to have socially desirable qualities (p < 0.004) were rated to have better PS and women patients (p < 0.004) to have worse PS. Clinicians having international work experience had increased concordance with ECOG PS rating. Qualitative results showed that ‘perceived socio-economic background of the patient’, ‘age of the patient’, ‘patient’s and family’s preferences’ and ‘past treatment response’ were the major themes highlighted by respondents that influenced the treatment-related decisions made by clinicians. Conclusion There is considerable variability in ECOG PS determined by clinicians. Decision-making in oncology is complex, multifactorial and is influenced by rater and patient-related factors.

e18659 Background: Surgery followed by chemoradiotherapy with temozolomide (TMZ) is the standard of care for glioblastoma. There are limited reports of quality metrics in glioblastoma. We present an audit of adherence to selected quality indicators proposed in the PRIME Quality Improvement study. Methods: Retrospective audit of quality indices for glioblastoma patients treated between 2017 - 2020. Patients were treated within a standard protocol of postsurgical integrated molecular diagnosis, radiotherapy with concurrent and adjuvant TMZ. Multiparametric MRI at predefined time-points of pre- and post radiation, interim and end of adjuvant TMZ guided management. Demographic, clinical, pathological, imaging, therapy and outcomes data was abstracted. Numbers with proportions for indices were calculated. Survival was estimated using the Kaplan Meier method. Results: Ninety-four glioblastoma patients were treated from 2017 to 2020. Quality metrics are reported (table). Patients in whom adjuvant TMZ could not be started or continued for 6 cycles had progressive disease and salvage chemotherapy was initiated. The 12 month overall and progression free survival was 74.6% (95% CI : 65.4% - 85.1%) and 43.6% (95% CI : 33.8% - 56.3%) respectively. Conclusions: Our patients met quality indices in most domains; outcomes are comparable with global results. These metrics will be periodically evaluated and updated to include newer standards to assess our continued service appropriateness.[Table: see text]

e24037 Background: Anatomical changes during the course of parotid sparing IMRT for head and neck cancer can lead to an increase in the actual dose absorbed by the parotid glands, which may be controlled with the use of interval adaptive replanning. In this prospective assessment of adaptive replanning for parotid dose changes, we explored the feasibility of carrying out adaptive replanning based on predefined objective dosimetric criteria at specified time points. We sought to assess the impact of this measure using a clinically meaningful endpoint of patient reported quality of life outcomes. Methods: 90 patients with head and neck radiotherapy indicated for definitive management or adjuvant therapy who had at least one parotid gland receiving a mean dose (MD) of between 25-30Gy were accrued in the study. The index parotid was delineated on the images acquired on 14th and 19th day and the MD was determined by overlaying the verification image on the planned CT. If the MD had increased by 2% of the initial intended dose, an adaptive plan was attempted with an aim to reduce MD by 2% without compromising PTV coverage; this plan was then used to deliver the remaining treatment. Patients were invited to complete QoL questionnaires: EORTC-QLQC30 with HN35 module, and XeQoL score at baseline, at 3 and 9 months after completion of treatment. Results: 46 out of 90 patients met the threshold for adaptive replanning and were switched to the new plan during treatment. Adaptive replanning was triggered at D14 for 31 patients and D19 for the remaining 15. Need for adaptive replanning was associated with receipt of concurrent chemotherapy and weight loss in the first two weeks of RT. QoL was evaluable for 50 patients at 3 months post treatment. In patients who required adaptive replanning per protocol, Mean XeQoL scores at 3 months showed significantly worse scores for overall scores (1.1 vs 2.3, p 0.001) and for the component individual physical, pain, psychological, and social domains. EORTC QLQ-C30 and HN35 questionnaires at 3 months also demonstrated significantly worse mean symptom scores of the relevant domains of mouth dryness (39 vs 60), stickiness (32 vs 54) and swallowing (39 vs 60) in patients who required adaptive replanning versus those who did not. No significant QoL trends were observable in the 31 patients who were evaluable at 9 months post treatment. The average time required for each step in the planning process was comparable for both the initial planning workflow and adaptive replanning process. Conclusions: The trigger criteria for replanning identified a population of patients who have significantly worsened quality of life due to radiation induced xerostomia. The benefits of adaptive replanning strategies based on weekly evaluation, binary thresholds and standard planning procedures is doubtful Clinical trial information: CTRI/2017/11/010683.

e18025 Background: The current approach to neck treatment in clinical T1-2 oral cancers is to offer elective nodal dissection to all patients, despite the fact that the majority of patients are pathologically node negative. This is due to the poor predictive ability of clinico-radiological assessment and subsequently poorer survival in those in whom neck dissection is omitted based on this. A robust prediction model for pathological nodal status may allow individualized decisions for neck dissection. Our aim was to develop a multiparameter prediction model to identify pathological node-negative status using machine learning. Methods: We identified 497 patients with cT1-2 oral cancer from a single institutional database from 2011-2018 who underwent primary resection and neck dissection. We compared the sensitivity, positive predictive value and accuracy of prediction of pathologically negative neck from clinico-radiological staging alone vs. a model created from multiple parameters including clinical features (clinico-radiological nodal status, ages, sex, subsite of primary lesion) and pathological features of the resected primary tumor (maximum dimension, depth of invasion, lymphovascular invasion, perineural invasion, grade and margins of resection). The multiparameter model was built from a training dataset of the first 400 patients using an ensemble of logistic regression, random forests and support vector machines. A cohort of 97 patients was used for independent validation. Results: In this cohort 232 (47%) were clinico-radiologically node negative, while 307(62%) were pathologically node negative. The sensitivity, positive predictive value and accuracy of the clinico-radiologically assigned nodal status was 56%, 74% and 61%, while that of the multiparameter machine learning model was 87%, 89% and 89% respectively. The area under curve (AUC) of the clinico-radiological prediction was 0.62 whereas that of the multiparameter predictive model was 0.91. In the validation dataset, 58/62 pathologically node negative patients were predicted correctly by the model. The accuracy of the model on the external validation dataset was 82%. Conclusions: The performance of the multiparameter predictive model was considerably superior to clinico-radiological neck staging for prediction of pathological node negative neck. This could be validated on an independent dataset. This could be considered for prospective clinical evaluation of individualized neck dissection.

Human papillomavirus (HPV) associated head and neck squamous cell cancers (HNSCC) have become increasingly common in the West, but the same cannot be said about India. These cancers have a different biology and confer a better prognosis, however, its current role in the management of patients in India is not clearly defined. At the 35th Indian Cooperative Oncology Network conference held in September 2016, a panel of radiation, surgical and medical oncologists, pathologists, and basic scientists from across the country having experience in clinical research with respect to HPV in HNSCC reviewed the available literature from India. All the ideas and facts were thereafter collated in this report. Various topics of controversy in dealing with the diagnosis and management of HPV-associated HNSCC have been highlighted in this report in context to the Indian scenario. Furthermore, the prevalence of the same and its association with tobacco and high-risk sexual behavior has been touched on. Conclusively, a set of recommendations has been proposed by the panel to guide the practicing oncologists of the country while dealing with HPV-associated HNSCC.

Aims To report the acute toxicity and the dosimetric correlates after moderately hypofractionated radiotherapy for localized prostate cancer. Methods A total of 101 patients with localized prostate cancer were treated with image-guided intensity-modulated radiation therapy. Patients were treated to 65 Gy/25 Fr/5 weeks ( n = 18), or 60 Gy/20 Fr/4 weeks ( n = 83). Most (82.2%) had high-risk or pelvic node-positive disease. Acute toxicity was assessed using Radiation Therapy Oncology Group (RTOG) acute morbidity scoring criteria. Dose thresholds for acute rectal and bladder toxicity were identified. Results The incidence of acute grade 2 GI toxicity was 20.8%, and grade 2 genitourinary (GU) toxicity was 6.9%. No Grade 3 to 4 toxicity occurred. Small bowel toxicity was uncommon (Gr 2 = 4%). The 2 Gy equivalent doses (EQD2) to the rectum and bladder (α/β = 3) calculated showed that the absolute doses were more consistent predictors of acute toxicities than the relative volumes. Those with grade 2 or more GI symptoms had significantly higher V EQD2-60 Gy (13.2 vs 9.9 cc, p = 0.007) and V EQD2-50 Gy (20.6 vs 15.4 cc, p = 0.005). Those with grade 2 or more GU symptoms had significantly higher V EQD2-70 Gy (30.4 vs 18.4 cc, p = 0.001) and V EQD2-65 Gy (44.0 vs 28.8 cc, p = 0.001). The optimal cutoff value for predicting grade 2 acute proctitis, for V EQD2-60 Gy was 9.7 cc and for V EQD2-50 Gy was 15.9 cc. For grade 2 GU symptoms, the threshold values were 23.6 cc for V EQD2-70 Gy and 38.1 cc for V EQD2-65 Gy . Conclusions Hypofractionated radiotherapy for prostate cancer is well tolerated and associated with manageable acute side effects. The absolute dose-volume parameters of rectum and bladder predict for acute toxicities.

Neoadjuvant chemotherapy (NACT) for locally advanced breast cancer (LABC), apart from increasing breast conservation rates, also provides an opportunity to assess tumour response to chemotherapy, with Pathological Complete Response (pCR) described as an independent prognostic factor and a surrogate marker for better outcome and survival. Our primary aim was to identify clinical and pathological factors associated with pCR following NACT in patients with LABC treated at our institution. Our secondary aim was to analyze the impact of pCR and associated factors on disease free survival (DFS) and overall survival (OS). A retrospective analysis of LABC patients treated with NACT between Jun 2011 and Dec 2013. Clinical and histological variables were analyzed for association with pCR (no invasive or in situ carcinoma in breast or axillary lymph nodes). Kaplan-Meier curves and Cox regression model was used for survival analysis. All values were twosided, and statistical significance was defined as p

Background: While the incidence of breast cancer in men is up to 100-fold less than in women, it is estimated that in 2020, 2,620 men in the United States will be diagnosed with breast cancer, and 520 will die from this disease. However, male patients are rarely included in breast cancer clinical trials and treatment guidelines for this population are often proposed based on data from female patients. Ribociclib (RIB), an oral, selective cyclin-dependent kinase 4/6 inhibitor, is approved for use in combination with endocrine therapy (ET) in women with HR+, HER2- ABC. Here, we present a subgroup analysis of male patients from the Core Phase of CompLEEment-1 (NCT02941926), a Phase IIIb trial of RIB in combination with letrozole (LET) in patients with HR+, HER2- ABC. In order to reflect a more typical real-world clinical setting, the eligibility criteria for this study allowed for a more diverse and broader patient population than those of previous Phase III trials of RIB + LET. Methods: CompLEEment-1 included women of any menopausal status and men with HR+, HER2- ABC treated with ≤1 line of prior chemotherapy and no prior hormonal therapy for advanced disease. Pts received RIB (600 mg QD, 3 weeks on/1 week off) in combination with LET (2.5 mg QD, continuous). Men and premenopausal women received a luteinizing hormone-releasing hormone agonist (3.6 mg goserelin or 7.5 mg leuprolide, Q28D). This subgroup analysis assessed the primary outcomes (safety and tolerability) and secondary outcomes of time to progression (TTP), overall response rate (ORR), and clinical benefit rate (CBR) in male patients. Results: At the data cutoff date (November 8, 2019), 39 male patients (1.2%; N = 3,246) had been evaluated, with a median duration of exposure to RIB of 19.2 months. Adverse events (AEs) were reported in 38 (97.4%) patients; with all but two experiencing a treatment-related AE. Grade ≥ 3 AEs were reported in 26 (66.7%) patients; serious AEs were reported in 6 patients. There were no treatment-related fatal AEs. The most common all-grade AEs were neutropenia (53.8%), hot flush (33.3%), and diarrhea (25.6%), with the most common grade ≥ 3 AE being neutropenia (41.0%). Overall, 7 patients (17.9%) had ≥ 1 dose reduction of RIB, all of whom had at least 1 due to an AE, and 18 patients (46.2%) permanently discontinued treatment, 4 (10.3%) due to AEs. Median TTP was not estimable (95% CI, 16.8-NE); event-free probability was 61.4% (95% CI, 38.4-77.9) at 30 months. For the 32 patients with measurable disease, ORR was 46.9% (95% CI, 29.1-65.3%) and CBR was 71.9% (95% CI, 53.3-86.3). Conclusions: In this subgroup analysis of male patients - a rare population who are often excluded from clinical trials - efficacy results support the use of RIB + LET in HR+, HER2- ABC in a close to real-world setting. The safety profile associated with RIB + LET was manageable, with very few patients discontinuing treatment due to AEs, consistent with previous Phase III trials of RIB + LET. Citation Format: Mario Campone, Michelino De Laurentiis, Claudio Zamagni, Igor Kudryavcev, Mariëtte Agterof, Ursa Brown-Glaberman, Markéta Pálácova, Sanjoy Chatterjee, Lakshmi Menon-Singh, Jiwen Wu, Katie Zhou, Miguel Martín. Ribociclib + letrozole in male patients with hormone receptor-positive (HR+), human epidermal growth factor receptor-2-negative (HER2−) advanced breast cancer (ABC): Subgroup analysis of the phase IIIb CompLEEment-1 trial [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS14-03.

Nodal metastasis is an important prognostic factor in oral squamous cell carcinoma (OSCC). Detailed topographic study of metastasis can guide surgical and adjuvant radiation treatment protocols.Retrospective analysis of distribution of nodal spread was done by auditing pathology records of 1004 patients who underwent primary surgical management at our center.The median nodal yield was 41 (range of 9-166) nodes, per patient. Metastasis was present in 42.9% patients, of which 52.3% demonstrated extranodal extension. Reclassification by AJCC8 criteria resulted in up-staging in 35.6% patients (pN1, pN2a, pN2b, pN2c, pN3a and pN3b in 13.1%, 3.7%, 6.9%, 0.9%, 0%, 18.1% respectively). Ipsilateral levels Ib and IIa were involved in a quarter of patients each, while IIb, IV and V were involved in 4%, 3% and 1% of patients, respectively. Contralateral nodal metastasis was present in 5.4%. Skip metastases to level IV were 2.2% and 1.2% for tongue and gingivobuccal primaries. Tongue primaries had a lower likelihood of involving level Ib, but higher of level IIa and III, compared to gingivobuccal primaries, and a lower likelihood of extranodal extension. Primary site did not influence nodal metastasis to levels IIb, IV or V, but other factors like lymphovascular invasion, pT stage and margin status had an influence.This large series with high nodal yield, shows low level of metastasis to level IIb, IV and V, which can help modify future guidelines for extent of surgery and avoid targeted adjuvant radiation to specific levels.

1055 Background: Real-world evidence is important as it complements data from randomized controlled trialse report updated results from CompLEEment-1, a Phase IIIb trial evaluating RIB+LET in an expanded population, the largest CDK4/6i trial in ABC to date. Methods: Patients (pts) with HR+, HER2– ABC, ≤ 1 line of prior CT and no prior ET for ABC received RIB+LET. Study design has been reported previously (De Laurentiis, et al. ASCO 2019). Primary endpoints were safety and tolerability. Results: 3,246 pts received ≥ 1 dose of study treatment. Median duration of follow-up was 25.4 months (mos) (15 additional mos since interim analysis [De Laurentiis, et al. ABC5 2019]). Median treatment exposure was 17.8 mos. Baseline characteristics indicated a diverse population, including men (1.2%), premenopausal women (22.2%), and pts aged ≥ 70 years (19.5%); 112 (3.5%) pts had an ECOG PS of 2, 194 (6.0%) pts received prior CT for ABC, and 51 (1.6%) pts had stable CNS lesions. The most common adverse events (AEs) were neutropenia (61.1%), nausea (35.9%), and fatigue (23.4%). Grade 3/4 hematologic abnormalities ( > 5.0 %) were decreased neutrophils (54.8%), leukocytes (25.9%), and lymphocytes (12.6%). Grade 3/4 biochemical abnormalities ( > 5.0 %) were increased ALT (9.1%) and AST (6.7%). An increase of > 60 ms in QTcF interval from baseline occurred in 189 (5.9%) pts, while post-baseline QTcF of > 480 to ≤ 500 ms and > 500 ms occurred in 59 (1.8%) and 42 (1.3%) pts, respectively. Treatment-related AEs led to treatment discontinuation in 418 (12.9%) pts. Of 74 (2.3%) on treatment deaths, 38 (1.2%) were due to breast cancer. Median time to progression was 27.1 mos (95% CI, 25.7-NE), overall response rate was 43.6% (95% CI, 41.5-45.8%), and clinical benefit rate was 69.1% (95% CI, 67.1-71.1%) for pts with measurable disease at baseline. Conclusions: This analysis confirms the safety and efficacy of RIB+LET in a large, diverse cohort of pts with HR+, HER2– ABC (with no previous ET for ABC), closely resembling real-world clinical practice. Safety and efficacy data were consistent with those observed in the MONALEESA trials, supporting the use of RIB+LET in the first-line setting. NCT02941926. Clinical trial information: NCT02941926 .

Radical radiotherapy (RT) with curative intent, with or without chemotherapy, is the standard treatment for inoperable, locally advanced nonsmall cell lung cancer (NSCLC).We retrospectively reviewed the data for all 288 patients who presented with inoperable, locally advanced NSCLC at our institution, between May 2011 and December 2016.RT alone or sequential chemoradiotherapy (SCRT) or concurrent chemoradiotherapy (CCRT) was used for 213 patients. Median age was 64 years (range: 27-88 years). Stage-III was the biggest stage group with 189 (88.7%) patients. Most patients with performance status (PS) 0 or 1 received CCRT, whereas most patients with PS 2 received RT alone (P0.001). CCRT, SCRT, and RT alone were used for 120 (56.3%), 24 (11.3%), and 69 (32.4%) patients, respectively. A third of all patients (32.4%) required either volumetric-modulated arc radiotherapy (VMAT) or tomotherapy. Median follow-up was 16 months. The median progression-free survival and median overall survival (OS) were 11 and 20 months, respectively. One-year OS and 2-year OS were 67.9% and 40.7%, respectively. Patients treated using CCRT lived significantly longer with a median survival of 28 months, compared with 13 months using SCRT and RT alone (P0.001). On multivariate analysis, OS was significantly affected by age, stage group, treatment approach, and response to treatment.RT including CCRT is feasible, safe, and well tolerated in our patient population and results in survival benefits comparable with published literature. CCRT should be considered for all patients with inoperable, locally advanced NSCLC, who are fit and have good PS.

Carcinoma of the gingivobuccal complex is one of the most common cancers in India and patients usually present in an advanced stage. There is limited data in literature regarding the factors predicting outcome in pathological T4a patients. In this study, we aimed to study the clinic-pathological factors which may influence treatment outcomes in pT4a patients. This is a retrospective study of 121 patients who underwent surgery for oral squamous cell carcinoma between August 2011 and December 2016, staged pT4a. Overall survival (OS) and disease-free survival (DFS) were analyzed for variables including age, depth of invasion, margin status, differentiation, nodal status, extranodal spread, lymphovascular and perineural spread, and adjuvant treatment. The study cohort comprised 93 males with mean age 60.28 years (S.D. 11.25). Median DFS was 21 months (range 9 to 2374 days) whereas median OS was 24.5 months (range 9 to 2374 days). On univariate analysis, lymphovascular invasion, perineural invasion, cervical nodal metastasis, and extranodal extension had a statistically significant effect on both DFS and OS. On multivariate analysis, age (p = 0.014) and adjuvant radiotherapy (p = 0.010) were the statistically significant factors affecting OS. None of the factors affected DFS on multivariate analysis. Patients staged pT4a with cervical nodal metastasis, extranodal extension, lymphovascular invasion, and perineural invasion have reduced OS and DFS. On multivariate analysis, lower age at presentation and adjuvant radiation improved patient outcome.

Sanjoy Chatterjee,1 Animesh Saha,1 Indu Arun,2 Sonali Susmita Nayak,2 Subir Sinha,3 Sanjit Agrawal,4 Mayur Parihar,5 Rosina Ahmed4 1Department of Radiation Oncology, 2Department of Pathology, 3Department of Medical Statistics, 4Department of Breast Surgery, 5Department of Molecular Pathology, Tata Medical Center, Kolkata, West Bengal, India Background: Following neoadjuvant chemotherapy (NACT) for breast cancer, changes in estrogen receptor (ER), progesterone receptor (PR), HER2 status, and Ki-67 index (IHC4 status) and its correlation with pathological complete response (pCR) or relapse-free survival (RFS) rates could lead to better understanding of tumor management. Patients and methods: Pre- and post-NACT IHC4 status and its changes were analyzed in 156 patients with breast cancer. Associations between pCR, RFS rates to IHC4 status pre- and post-NACT were investigated. Results: pCR was found in 25.3% patients. Both ER and PR positive tumors had the lowest (14.3%) pCR compared to ER and PR negative (29%) or either ER-/PR-positive (38.6%) tumors. PR positivity was significantly associated with less likelihood of pCR (15% versus 34%). The pCR rate was low for luminal A subtype (13.68%) compared to 24.36%, 26.31%, and 33.33% for luminal B, HER2-enriched, and triple-negative subtypes, respectively. There was significant reduction in ER expression and Ki-67 index post-NACT. RFS of patients in whom the hormonal status changed from positive to negative was better compared to those of patients in whom the hormonal status changed from negative to positive. Conclusion: Although changes in IHC4 occurred post-NACT, pre-NACT hazard ratio status prognosticated RFS better. pCR and RFS rates were lower in PR-positive tumors. Keywords: neoadjuvant chemotherapy, IHC4 status changes, survival&nbsp

Purpose This phase III study compared SB3, a trastuzumab (TRZ) biosimilar, with reference TRZ in patients with human epidermal growth factor receptor 2–positive early breast cancer in the neoadjuvant setting ( ClinicalTrials.gov identifier: NCT02149524). Patients and Methods Patients were randomly assigned to receive neoadjuvant SB3 or TRZ for eight cycles concurrently with chemotherapy (four cycles of docetaxel followed by four cycles of fluorouracil, epirubicin, and cyclophosphamide) followed by surgery, and then 10 cycles of adjuvant SB3 or TRZ. The primary objective was comparison of breast pathologic complete response (bpCR) rate in the per-protocol set; equivalence was declared if the 95% CI of the ratio was within 0.785 to 1.546 or the 95% CI of the difference was within ± 13%. Secondary end points included comparisons of total pathologic complete response rate, overall response rate, event-free survival, overall survival, safety, pharmacokinetics, and immunogenicity. Results Eight hundred patients were included in the per-protocol set (SB3, n = 402; TRZ, n = 398). The bpCR rates were 51.7% and 42.0% with SB3 and TRZ, respectively. The adjusted ratio of bpCR was 1.259 (95% CI, 1.085 to 1.460), which was within the predefined equivalence margins. The adjusted difference was 10.70% (95% CI, 4.13% to 17.26%), with the lower limit contained within and the upper limit outside the equivalence margin. The total pathologic complete response rates were 45.8% and 35.8% and the overall response rates were 96.3% and 91.2% with SB3 and TRZ, respectively. Overall, 96.6% and 95.2% of patients experienced one or more adverse event, 10.5% and 10.7% had a serious adverse event, and 0.7% and 0.0% had antidrug antibodies (up to cycle 9) with SB3 and TRZ, respectively. Conclusion Equivalence for efficacy was demonstrated between SB3 and TRZ on the basis of the ratio of bpCR rates. Safety and immunogenicity were comparable.

Objective: Technological advances have enabled clinicians to explore dose escalation strategies in various tumor sites. Intermediate and high risk oropharyngeal cancers have poor 5 year outcomes. This study aimed to assess the feasibility and dosimetric safety of 9% dose escalation in these tumors and compare the dose received by organs at risk (OAR) in escalated plans (67.2 Gy/28 fractions) versus (65 Gy/30 fractions) standard dose plans. Materials and Methods: FDG-PET fused datasets were used to delineate gross, clinical and planning target volumes. Standard dose plans were created using two non IMRT techniques (conventional and field in field plans) whilst the patient was treated using a helical tomotherapy plan. A fourth dose escalation plan was obtained allowing comparison between the 20 plans of oropharyngeal cancer patients. Results: It was feasible to escalate dose to the FDG-PET avid tumor within the set constraints to that of planning target volume and OAR. Comparison of the escalated dose to that of standard plans showed a statistically significant (P < 0.05) sparing of the mastication apparatus (MA) with escalated plans. Dose to the other critical and functional organs were comparable between the four plans. Conclusion: Hypofractionated, slightly accelerated dose escalation in oropharyngeal cancers is likely to be safe and the chance of trismus is not any higher than when standard dose radiotherapy is used. Active measures to reduce dose to the MA achieves acceptable dose volume parameters even at escalated doses.

Background The equivalent efficacy between SB3, a proposed trastuzumab biosimilar, and the trastuzumab reference product (TRZ) in terms of the breast pathologic complete response rate after neoadjuvant therapy in patients with early or locally advanced human epidermal growth factor receptor 2-positive breast cancer was demonstrated in the previous report. Here, we report the final safety, immunogenicity and survival results after neoadjuvant-adjuvant treatment. Patients and methods Patients were randomised 1:1 to receive neoadjuvant SB3 or TRZ for 8 cycles concurrently with chemotherapy (4 cycles of docetaxel followed by 4 cycles of 5-fluorouracil/epirubicin/cyclophosphamide). Patients then underwent surgery, followed by 10 cycles of adjuvant SB3 or TRZ as randomised. End-points included safety, immunogenicity, event-free survival (EFS) and overall survival through the adjuvant period. Results Of 875 patients randomised, 764 (SB3, n = 380; TRZ, n = 384) completed the study. The median follow-up duration was 437 days in the SB3 group and 438 days in the TRZ group. The incidence of treatment-emergent adverse events was comparable between groups (SB3, 97.5%; TRZ, 96.1%) during the overall study period. Up to the end of study, the overall incidence of antidrug antibody was low in both treatment groups (3 patients each). EFS was comparable between groups with a hazard ratio (SB3/TRZ) of 0.94 (95% confidence interval, 0.59–1.51) and EFS rates at 12 months of 93.7% for SB3 and 93.4% for TRZ. Conclusions Final safety, immunogenicity and survival results of this study further support the biosimilarity established between SB3 and TRZ. Trial registration ClinicalTrials.gov ( NCT02149524 ); EudraCT ( 2013-004172-35 ).

Context: Women undergoing treatment for breast cancer often have psychological morbidity and body image difficulties. The risk factors for increased levels of stigma in women with breast cancer have not been adequately studied. Aims: This study aimed at investigating the associations of high levels of stigma in women with breast cancer. Settings and Design: This cross-sectional study was conducted in a comprehensive cancer center in India and recruited women (n = 134) undergoing surgical treatment for breast cancer. Methods: Body image difficulties, including stigma and affective symptoms, were quantified, alongside disease- and treatment-related variables using standardized questionnaires. Statistical Analysis Used: Univariate analysis followed by multivariate logistic regression was performed to find the risk factors of high levels of stigma related to body image. Results: In the univariate analysis, high levels of stigma were associated with lesser educational attainment (odds ratio [OR] =2.92, confidence interval [CI] 1.25–6.8, P = 0.01), breast conservation surgery (BCS) as opposed to mastectomy (OR = 4.78, CI 2.07–11.03, P < 0.001), having an anxiety disorder (OR = 2.4, CI 1.09–5.33, P = 0.03), and depression (OR = 3.08, CI 1.37–6.89, P < 0.01). On multivariate logistic regression, with stigma as the dependent variable, being less educated (adjusted OR [AOR] 3.08, CI 1.18–8.04, P = 0.02) and opting for BCS (AOR 6.12, CI 2.41–15.5, P < 0.001) were associated with higher stigma. Conclusions: Women with breast cancer should be screened for distress and stigma. Women opting for BCS may still have unmet emotional needs on completion of surgery and should have access to psychological interventions to address stigma, affective symptoms, and body image problems.

Background There is an unmet need to assess efficacy and safety of therapies for ABC in men. The cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitor RIB has been approved for use in combination with LET for the treatment of HR+, HER2– ABC in men and postmenopausal women with no prior therapy for advanced disease. Here we present a subgroup analysis of male pts in CompLEEment-1, an open-label, phase 3b trial evaluating RIB + LET as first-line therapy in a pt population with broad inclusion/exclusion criteria to reflect real-world practice. Methods Pts with HR+, HER2– ABC and no prior hormonal therapy for ABC received RIB (600 mg daily [QD], 3 weeks on/1 week off) + LET (2.5 mg QD, continuous), and concomitant goserelin or leuprolide. Safety and tolerability (primary outcome), overall response rate (ORR), and clinical benefit rate (CBR) were analyzed for male pts in a subgroup analysis. Results There were 39 men in the study. The median follow-up was 10.35 months, and the median duration of exposure to RIB was 8.0 months. Any-grade adverse events (AEs) were reported in 38 pts; 36 AEs were treatment-related. Serious AEs (SAEs) were reported in 4 pts; 1 SAE was related to treatment. No fatal treatment-related SAEs were reported. Most common any-grade AEs (≥ 20%) were neutropenia (n = 14), hot flush (n = 12), diarrhea (n = 10), and fatigue (n = 8). There were 31 pts with at least 1 dose adjustment of RIB; 5 reductions and 27 interruptions were due to AEs. Fourteen pts permanently discontinued treatment: 7 due to progressive disease and 4 due to AEs. ORR in pts with measurable disease was 34.4% (95% confidence interval [CI], 18.6-53.2%), and CBR was 68.8% (95% CI, 50.0-83.9%). Median TTP was not reached. Conclusions This subgroup analysis from CompLEEment-1 supports the safety and efficacy of RIB + LET in men with HR+, HER2– ABC, and adds to the clinical understanding of CDK4/6 inhibitors in men with HR+, HER2– ABC. Clinical trial identification NCT02941926. Editorial acknowledgement Medical editorial assistance was provided by Rob Camp, PhD, of Healthcare Consultancy Group, LLC, and funded by Novartis Pharmaceuticals Corporation. Legal entity responsible for the study Novartis. Funding Novartis Pharmaceuticals. Disclosure M. Campone: Speaker Bureau / Expert testimony: Novartis; Advisory / Consultancy: Lilly. M. De Laurentiis: Honoraria (institution), Advisory / Consultancy: Pfizer; Honoraria (institution), Advisory / Consultancy: Novartis; Honoraria (institution), Advisory / Consultancy: Roche; Honoraria (institution), Advisory / Consultancy: Celgene; Honoraria (institution), Advisory / Consultancy: AstraZeneca. C. Zamagni: Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Advisory / Consultancy: Eisai; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Novartis; Advisory / Consultancy, Research grant / Funding (institution): Pfizer; Advisory / Consultancy: PharmaMar; Advisory / Consultancy, Travel / Accommodation / Expenses: Pierre Fabre; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Roche; Research grant / Funding (institution): Abbvie; Research grant / Funding (institution): Array BioPharma; Research grant / Funding (institution), Travel / Accommodation / Expenses: Celgene; Research grant / Funding (institution): Medivation; Research grant / Funding (institution): Morphotek; Research grant / Funding (institution): Roche/Genentech. M. Agterof: Advisory / Consultancy: Roche. M. Martin: Advisory / Consultancy, Speaker Bureau / Expert testimony: Pfizer; Advisory / Consultancy, Speaker Bureau / Expert testimony: AstraZeneca; Advisory / Consultancy, Speaker Bureau / Expert testimony: Lilly; Advisory / Consultancy: Puma; Advisory / Consultancy: PharmaMar; Advisory / Consultancy, Speaker Bureau / Expert testimony: Novartis; Advisory / Consultancy: Roche-Genentech; Advisory / Consultancy: Taiho Oncology. All other authors have declared no conflicts of interest.

1041 Background: RIBO, an oral, selective inhibitor of CDK4/6 (CDK4/6i), is approved for use in combination with endocrine therapy (ET) in women with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2–) ABC in multiple countries worldwide. Here we report interim safety and efficacy results from CompLEEment-1, a phase 3b trial evaluating RIBO+LET in an expanded patient (pt) population and the largest CDK4/6i trial in ABC to date. Methods: Pts with HR+, HER2– ABC, ≤1 line of prior chemotherapy (CT), and no prior ET for ABC received RIBO+LET. Treatment regimens and study endpoints have been reported previously (De Laurentiis, et al. ASCO 2018. Poster 1056). Results: Overall, 3,246 pts, who received ≥1 dose of study treatment, were evaluated (cut-off date, August 8, 2018). Median duration of RIBO exposure was 8.1 months (min, 0.0; max, 22.4). Demographic and baseline characteristics indicated a diverse population including men (1.2%), premenopausal women (22.2%), and patients aged ≥70 years (19.5%). Pts were well represented in terms of age, race, and disease history; 5.9% of pts received prior CT for ABC. The only non-hematologic any-cause grade ≥3 AEs ≥5% were increased alanine (7.3%) and aspartate (5.3%) aminotransferase. Treatment-related AEs (any grade) led to discontinuation in 11.4% of pts. Of the 51 (1.6%) on-treatment deaths, 26 were due to study indication and 25 to other reasons. The median time to progression was not estimable (NE) (95% confidence interval [CI], 17.1-NE). Overall response rate was 20.5% (95% CI, 19.1%-21.9%) and clinical benefit rate was 66.1% (95% CI, 64.4%-67.7%). Consistent mean change from baseline in Functional Assessment of Cancer Therapy – Breast Cancer questionnaire scores indicated that pts maintained their quality of life throughout treatment. Conclusions: This interim analysis demonstrates the safety, tolerability, and efficacy of RIBO+LET in a large, diverse cohort of pts with HR+, HER2– ABC who had not previously received ET for ABC. Safety results were consistent with those observed in RIBO pivotal studies and no new safety signals were observed. Clinical trial information: NCT02941926.

OBJECTIVE: Intensity modulated radiotherapy (IMRT) is used, where necessary, for bulky or complex-shaped, locally advanced, non-small cell lung cancer (NSCLC). We evaluate our real-world experience with radical radiotherapy including concurrent chemoradiation (CCRT), and analyse the impact of IMRT on survival outcomes in patients with larger volume disease. METHODS: All patients treated between May 2011 and December 2017 were included. Analyses were conducted for factors affecting survival, including large volume disease that was defined as planning target volume (PTV) > 500 cc. RESULTS: In 184 patients with large volume disease, the median overall survival was 19.2 months, compared to 22 months seen with the overall cohort of 251 patients who received radical radiotherapy. PTV and using CCRT were significant predictors for survival. IMRT was used in 93 (50.5%) of 184 patients with large PTV. The patients treated using IMRT had significantly larger disease volume (median PTV = 859 vs 716 cc; p-value = 0.009) and more advanced stage (proportion of Stage IIIB: 56 vs 29%; p-value = 0.003) compared to patients treated with three-dimensional conformal radiotherapy. Yet, the outcomes with IMRT were non-inferior to those treated with 3DCRT. CCRT was used in 103 (56%) patients with large volume disease and resulted in a significantly better median survival of 24.9 months. The proportional benefit from CCRT was also greater than in the overall cohort. CONCLUSION: Despite being used for larger volume and more advanced NSCLC, inverse-planned IMRT resulted in non-inferior survival. ADVANCES IN KNOWLEDGE: IMRT enables the safe use of curative CCRT for large-volume, locally-advanced NSCLC.

Salivary ductal carcinomas (SDCs) are extremely rare and aggressive malignancies, accounting for approximately 6% of all salivary gland malignancies. One distinct feature is their resemblance to ductal carcinomas of breast. A significant percentage of SDCs overexpress Her2 and the use of targeted therapy with trastuzumab can be considered in these patients. We report a rare case of long term disease control with trastuzumab in Her2 positive metastatic parotid ductal carcinoma. Our case also highlights that isolated brain metastasis should be managed aggressively to allow optimal local control when systemic disease is under remission with trastuzumab. We have also reviewed the published literature on the use of trastuzumab in SDCs.

Aims Nutritional compromise is common during high dose radiotherapy (RT) or chemoradiotherapy (CRT) for head and neck cancers. We aimed to identify the factors that determine nutritional outcome for head and neck cancer patients during radiotherapy. Methods Data from 103 patients with head and neck cancer treated with highly conformal radiotherapy to doses of 60 Gy or more in 30–33 fractions in the adjuvant or definitive setting was analyzed. All patients received complex 3D conformal radiotherapy (3DCRT) or intensity modulated radiotherapy (IMRT). Patients received regular nutritional counseling and need-based interventions. Their weight was recorded at the beginning and end of radiotherapy. Using univariate and multivariate models we tested possible predictors of weight loss of >5% and NG tube requirement. Results The mean weight loss was 3.8%. The incidence of weight loss >5% was 37.9% and NG tube placement was 24.3%. The factors significantly associated with >5% weight loss in the univariate analysis were tumor site (oro-hypopharyngeal vs. others), definitive vs. adjuvant RT; prescription dose of >60 Gy vs. 60 Gy; CRT vs. RT alone; prescription dose planning target volume (PTV) volume >235 cc and total PTV volume >615 cc. Age, sex, T stage, N stage and modality (3DCRT/IMRT) were not significant. In multivariate analysis, the total PTV volume, prescription dose PTV volume and use of chemotherapy were significant after controlling for other factors. Patients could be risk stratified based on the use of CRT and large PTV volumes. Patients with none, one or both factors had a likelihood of >5% weight loss of 0%, 30.3%, and 56.9% ( p p = 0.007). Conclusions It is possible to predict weight loss and NG tube requirements from disease and treatment related factors. PTV volumes are important predictors of nutritional compromise. Risk stratification may enable more focused counseling and identification of patients who require preventive interventions.

Contrast-enhanced computed tomography (CECT) is the current standard for delineating tumours of the head and neck for radiotherapy. Although metabolic imaging with positron emission tomography (PET) has been used in recent years, the studies were non-confirmatory in establishing its routine role in radiotherapy planning in the modern era. This study explored the difference in gross tumour volume and clinical target volume definitions for the primary and nodal volumes when FDG PET/CT was used as compared with CECT in oropharyngeal cancer cases.Twenty patients with oropharyngeal cancers had a PET/CT scan in the treatment position after consent. Target volumes were defined on CECT scans by a consultant clinical oncologist who was blind to the PET scans. After obtaining inputs from a radiologist, another set of target volumes were outlined on the PET/CT data set. The gross and clinical target volumes as defined on the two data sets were then analysed. The hypothesis of more accurate target delineation, preventing geographical miss and comparative overlap volumes between CECT and PET/CT, was explored. The study also analysed the volumes of intersection and analysed whether there was any TNM stage migration when PET/CT was used as compared with CECT for planning.In 17 of 20 patients, the TNM stage was not altered when adding FDG PET information to CT. PET information prevented geographical miss in two patients and identified distant metastases in one case. PET/CT gross tumour volumes were smaller than CECT volumes (mean ± standard deviation: 25.16 cm(3) ± 35.8 versus 36.56 cm(3) ± 44.14; P0.015) for the primary tumour. Interestingly, our study showed no significant differences in gross tumour volume for T1/T2 disease, although differences in gross tumour volumes for advanced disease (T3/T4) were significant. The nodal target volumes (mean ± standard deviation: CECT versus PET/CT 32.48 cm(3) ± 36.63 versus 32.21 cm(3) ± 37.09; P0.86) were not statistically different. Similarity and discordance coefficients were calculated and are reported.PET/CT as compared with CECT could provide more clinically relevant information and prevent geographical miss when used for radiotherapy planning for advanced oropharyngeal tumours. Also, PET/CT provided a smaller better-defined target volume when compared with CECT. PET/CT-based volumes could therefore be used for treatment planning and targeted dose painting in oropharyngeal cancers.

Background: Sentinel lymph node (SLN) biopsy accurately stages the axilla, but is time consuming and resource intensive. Nomograms and scoring systems have been developed, based on clinical and pathologic data available before surgery, to attempt to predict the likelihood of lymph node metastasis before surgery. As the management of the axilla in patients with low nodal burden changes, it is also important to predict whether there will be further axillary disease in patients with a positive SLN. Aim: To explore the risk factors for SLN and non-SLN metastasis in Indian women with breast cancer, by analysis of clinical and pathologic data. To assess the validity and clinical utility of two MSKCC nomograms that predicts axillary lymph node status for Western patients. Methods: Clinical data, and pathologic data available from core biopsy, for a consecutive series of women having SLNB was analyzed, and was plotted on two MSKCC nomograms. Univariate analysis was done by χ2 and Fischer exact tests and multivariate analysis was done by logistic regression method. A receiver-operating characteristic (ROC) curve was drawn and predictive accuracy was assessed by calculating the area under the ROC curve (AUC). Results: 34% (89 out of 256) of our patients had SLN positivity. When correlated with SLN metastasis by univariate analysis, LVI (χ2 = 80, P ≤ 0.001), PNI (χ2 = 13.36, P ≤ 0.001), ER+ (χ2 = 6.85, P = 0.009), PR+ (χ2 = 7.1, P = 0.008) and age ( P = 0.03) were significant. However, multivariate analysis showed that age (OR=1.04, P = 0.007) and LVI (OR=0.07, P ≤ 0.001) were identified as independent predictors for SLN metastasis. The area under the ROC curve was 0.772 and it fairly correlated with MSKCC nomogram. Patients with MSKCC scores lower than 38% had a frequency of SLN metastasis of 7.7% (5/65) and this cut-off could be used as a guide for not doing frozen section analysis in this subgroup. Further axillary dissection showed 41% (38 out of 92) had non-sentinel nodes positive. When correlated with non-SLN metastasis by univariate analysis, LVI (χ2 = 8.8, P = 0.003), PNI (χ2 = 6.85, P = 0.009), and extracapsular extension (χ2 = 4.18, P = 0.04) were significant. Number of SLN negative ( P = 0.01), SLN ratio (number of SLN positive/total number of SLN removed) ( P = 0.01) and size of SLN metastasis ( P = 0.002) were significant. However, multivariate analysis showed that only size of SLN metastasis (OR=0.845, P = 0.02) was identified as independent predictor for non-SLN metastasis. The area under the ROC curve was 0.66 and it poorly correlated with MSKCC nomogram. Conclusion: The MSKCC nomogram can provide a fairly accurate prediction of the probability of SLN metastasis, but is not for non-SLN metastasis. An institutional nomogram for non-SLN metastasis, including additional factors such as size of SLN metastasis, may improve prediction.

e13104Background: Serial monitoring of CA 15-3 levels can be used as a marker of disease activity in MBC. But the utility over and above image based monitoring remains controversial. We analyzed if...

e13128Background: Contrary to earlier published data using manual IHC methods, we had reported Triple negative breast cancer (TNBC) rates of 11-15% as in western literature. Here we report the demo...

e12613Background: Trials of breast surgery in metastatic breast cancer (MBC) have failed to improve outcomes. RT to the breast could provide local palliation with a hypothetical benefit to progress...