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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.

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.

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.

Mucinous carcinoma (MC) of the breast is very rare (∼1-7% of all breast cancers), invasive ductal carcinoma. Presence of pools of extracellular mucin is one of the most important histological features for MC. This paper aims at developing a quantitative computer-aided methodology for automated identification of mucin areas and its percentage using tissue histological images. The proposed method includes pre-processing (i.e., colour space transformation and colour normalization), mucin regions segmentation, post-processing, and performance evaluation. The proposed algorithm achieved 97.74% segmentation accuracy in comparison to ground truths. In addition, the percentage of mucin present in the tissue regions is calculated by the mucin index (MI) for grading MC (pure, moderately, minimally mucinous).

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.

Background and objective In this study, we have analysed pretreatment positron-emission tomography/ computed tomography (PET/CT) images of head and neck squamous cell carcinoma (HNSCC) patients. We have used a publicly available dataset for our analysis. The clinical features of the patient, PET quantitative parameters, and textural indices from pretreatment PET-CT images are selected for the study. The main objective of the study is to use classifiers to predict the outcome for HNSCC patients and compare the performance of the model with the conventional statistical model (CoxPH). Methods We have applied a 40% fixed SUV threshold method for tumour delineation. Clinical features of each patient are provided in the dataset, and other features are calculated using LIFEx software. For predicting the outcome, we have implemented three classifiers - Random Forest classifier, Gradient Boosted Decision tree (GBDT) and Decision tree classifier. We have trained each model using 93 data points and test the model performance using 39 data points. The best model - GBDT is chosen based on the performance metrics. Results It is observed that typically three features: MTV (Metabolic tumour Volume), primary tumour site and GLCM_correlation are significant for prediction of survival outcome. For testing cohort, GBDT achieves a balanced accuracy of 88%, where conventional statistical model reported a balanced accuracy of 81.5%. Conclusions The proposed classifier achieves higher accuracy than the state of the art technique. Using this classifier we can estimate the HNSCC patient’s outcome, and depending upon the outcome treatment policy can be selected.

Estrogen and progesterone receptors serve as an important predictive and prognostic biomarkers for breast cancer immunohistological analysis. For breast cancer prognosis, pathologists manually compute the score based on the visual expression and the number of immunopositive and immunonegative nuclei. This manual scoring technique is time-consuming, cumbersome, expensive, error-prone, and susceptible to intra- and interobserver ambiguities. To solve these issues, we proposed a deep neural network (i.e., HscoreNet), which consists of three parts, i.e., encoder, decoder, and scoring layer. A total of 600 (300 ER and 300 PR) regions of interest at 40 × magnification from 100 histologically confirmed slides were used in this study. The size of each region of interest was 2048 × 1536 pixels (width × height). The encoder layer has been used to transform input pixels into a lower-dimensional representation, whereas the decoder reconstructs the output of the encoder through minimization of a cost function. The decoder generates an image that only contains immunopositive and immunonegative nuclei. The output of the decoder is fed to the input of the scoring layer. This layer computes the Histo-score or H-score based on the staining intensity, the color expression, and the number of immunopositive and immunonegative nuclei. Pathologists compute this score to subcategorize the cancer grades and to decide proper treatment procedures. Our proposed approach is affordable, accurate, and fast. We achieved excellent performance, with 95.87% precision and 94.53% classification accuracy. Our proposed approach streamlines the human error-prone and time-consuming process. This methodology can also be used for other types of histology and immunohistology image segmentation and scoring.

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.

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.