SALTT study: A retrospective analysis of 111 SAlivary gland tumors of Lung and Tracheobronchial Tree.

INTRODUCTION: Primary pulmonary salivary gland-type tumours (PPSGT) are rare lung neoplasms arising from submucosal seromucinous glands in the central airway. METHODS AND RESULTS: We retrospectively analysed the clinicopathological features of 111 PPSGTs diagnosed at our institute between 2003 and 2021. The mean age at diagnosis was 43.8 years(range 6-78 years) and a male-to-female ratio of 2:1. On imaging, 92 % of cases had centrally located tumours and 37.3 % were early stage. The histopathological types included 70 cases (63 %) of mucoepidermoid carcinoma (MEC), 31 cases (27.7 %) of adenoid cystic carcinoma (ADCC), two cases of myoepithelial carcinoma, one case each of acinic cell carcinoma (ACC), clear cell carcinoma (CCC), epithelial myoepithelial carcinoma (EMC) and 5 others [including adenocarcinoma of minor salivary gland origin(n = 3), carcinoma with sebaceous differentiation(n = 1) and poorly differentiated carcinoma of salivary gland type(n = 1)]. The size of the tumours found in the resection specimens ranged from 1 cm to 13 cm, with an average size of 4.9 cm. High-risk attributes such as lymphovascular invasion (LVI), perineural invasion (PNI), pleural involvement, positive resection margins, and nodal metastasis were identified in 15.3 %, 15.3 %, 13.6 %,15.2 % and 6.7 % of cases, respectively. These attributes were found to be more frequent in ADCC than in MEC. Surgery was the main treatment modality [68/84 (80 %) cases]. ADCC cases had more recurrence and distant metastasis than MEC cases. The 3- year overall-survival (OS) and recurrence-free survival(RFS) were better in patients with age lesser than 60 years(p-value <0.0001), low pT stage (p-value 0.00038) and lower grade of MEC(p-value-0.0067). CONCLUSION: It is crucial to have an acquaintance with the morphologic spectrum and immunophenotypic characteristics of PPSGT to recognize them in this unusual location. In tandem, it is crucial to differentiate them from conventional primary non-small cell lung carcinoma, as the management protocols and prognostic implications differ significantly.

Volumetric and geometric changes in the parotid glands and target volume during image-guided radiotherapy for locally advanced oropharyngeal cancers.

PURPOSE: This study aimed to evaluate the volumetric and geometric changes in the parotid glands and target volume during image-guided radiotherapy (IGRT) for locally advanced oropharyngeal cancers. MATERIALS AND METHODS: Twenty patients receiving radiotherapy using IGRT at a dose of 70 Gy/35 fractions/7 weeks for locally advanced oropharyngeal cancers were accrued. Radiotherapy planning computed tomography (CT) scans were performed at pre-radiotherapy (RT), 20, 40, and 60 Gy for each patient. Volume changes in target and parotids along with shifts of parotids were assessed with respect to pre-RT scan after co-registration. In study scans, GTVp and GTVn were recontoured as per particular CT. CTV and PTV were copied from planning CT to study CT. CTV was edited from anatomical barriers, and PTV was edited only from the skin in the study CT. The parotids were recontoured on each study scan. The center of mass (COM) of C2 vertebral body was considered as the reference to evaluate its shifts. RESULTS: There was a statistically significant percentage regression of ipsilateral and contralateral parotid mean volumes at the rate of 0.85%/0.207 cc and 0.98%/0.26 cc per day, respectively. We observed the mean medial shift of center of mass of ipsilateral parotid of 2.23 mm (p = 0.011) and contralateral parotid of 2.67 mm (p = 0.069) at the end of 60 Gy. GTVp (mean) reduced from 41.87 cc at 0 Gy to 31.13 cc (25.65%) at 60 Gy (p = 0.003), while GTVn (mean) reduced from 19.98 cc at 0 Gy to 10.79 cc (45.99%) at 60 Gy (p = 0.003). There was a statistically significant reduction in CTV and PTV volumes at 60 Gy. CONCLUSION: Statistically significant volumetric and geometric changes occurred during intensity-modulated radiation (IMRT), which were most prominent after 40 Gy and were maximum at 60 Gy. There was a medial shift of parotid glands toward the high-dose region. This study can be useful to devise an adaptive radiotherapy strategy.

Clinical Implementation of "Plan of the Day" Strategy in Definitive Radiation Therapy of Cervical Cancer: Online Adaptation to Address the Challenge of Organ Filling Reproducibility.

PURPOSE: Definitive pelvic intensity modulated radiation therapy (IMRT) in cervical cancer is susceptible to geographic miss due to daily positional and volumetric variations in target and organs at risk. Hence, despite evidence of reduced acute and late treatment-related toxicities, implementation of image-guided IMRT (IG-IMRT) with a reasonable safety margin to encompass organ motion is challenging. METHODS AND MATERIALS: In this prospective, nonrandomized phase 2 study, patients with cervical cancer International Federation of Gynecology and Obstetrics (2009) stage IB2-IIIB between the ages of 18 and 65 years were treated with definitive pelvic chemoradiotherapy with a prespecified organ (bladder and rectum) filling protocol. Reproducibility of organ filling was assessed along with the implementation of daily comprehensive adaptive image-guided radiotherapy (IGRT), with a library of 3 IMRT (volumetric modulated arc therapy) plans with incremental expansions of clinical target volume (CTV) to planning target volume (PTV) (primary) margins (small, 0.7 cm; adequate, 1 cm; and large, 1.5 cm) and a backup motion robust 3-dimensional conformal radiotherapy plan; the appropriate plan is chosen based on pretreatment cone beam computed tomography (CBCT) ("plan of the day" approach). RESULTS: Fifty patients with a median age of 49 years (IQR, 45-56 years) received definitive radiation therapy (45-46 Gy in 23-25 fractions to pelvis, with simultaneous integrated boost to gross nodes in 15 patients) with the aforementioned IGRT protocol. In the analysis of 1171 CBCT images (in 1184 treatment sessions), the mean planning computed tomography (CT) and CBCT bladder volumes were 417 and 373 cc, respectively. Significant interfractional variation in bladder volume was noted with a mean absolute dispersion of 29.5% with respect to planning CT; significant influential random factors were postchemotherapy sessions (P ≤ .001), pre-CBCT protocol duration (P = .001), and grades of chemotherapy induced nausea vomiting (P = .001). Significantly higher variation in bladder filling was noted in patients with older age (P = .014) and larger planning CT bladder volume (P ≤ .001). Time trend analysis of fraction-wise bladder volume revealed an absolute systemic reduction of 16.3% in bladder volume means from the first to the fifth week. Variation in rectal diameter was much less pronounced, with 19.2% mean dispersion and without any significant factors affecting it. Although in 19% and 2% of sessions large IMRT PTV and 3-dimensional conformal radiotherapy were necessary to cover the primary target, respectively, reduction in treated volume was possible in 43% of sessions with small PTV selection instead of standard adequate PTV (36% sessions). Plan of the day selection had a moderate to strong correlation with nonabsolute dispersion of bladder filling (Spearman ρ =0.4; P = .001) and a weak (but significant) correlation with grades of acute toxicities. The planned protocol was well tolerated with no radiation-induced local grade 3 toxicity. CONCLUSIONS: Interfractional variation in organ filling (especially bladder) is inevitable despite fixed pretreatment protocol in definitive settings (intact cervix). Despite the logistical challenges, adaptive IGRT in the form of plan of the day based on incremental CTV-to-PTV margins is a relatively simple and feasible strategy to minimize geometric uncertainties in radical IG-IMRT of cervical cancer.

Intensity-Modulated Radiation Therapy Alone Versus Intensity-Modulated Radiation Therapy and Brachytherapy for Early-Stage Oropharyngeal Cancers: Results From a Randomized Controlled Trial.

PURPOSE: The objective of this study was to compare clinical outcomes of intensity-modulated radiation therapy (IMRT) alone versus IMRT + brachytherapy (BT) in patients with T1-T2N0M0 oropharyngeal squamous cell cancers (OPSCC). METHODS AND MATERIALS: This open-label randomized controlled trial was conducted at Tata Memorial Hospital, Mumbai, India. Patients with stage I and II OPSCC were considered for IMRT to a dose of 50 Gy/25 fractions/5 weeks in phase I followed by randomization (1:1) to further treatment with IMRT (20 Gy/10 fractions/2 weeks) or BT (192Ir high dose rate, 21 Gy/7 fractions/2 fractions per day). The primary endpoint of the trial was the reduction in xerostomia at 6 months evaluated using 99mTc salivary scintigraphy. Severe salivary toxicity (xerostomia) was defined as posttreatment salivary excretion fraction ratio <45%. Secondary endpoints were local control, disease-free survival, and overall survival. RESULTS: Between November 2010 and February 2020, 90 patients were randomized to IMRT (n = 46) alone or IMRT + BT (n = 44). Eleven patients (8 residual/recurrent disease, 2 lost to follow-up, 1 second primary) in the IMRT arm and 9 patients (8 residual/recurrence, 1 lost to follow-up) in the BT arm were not evaluable at 6 months for the primary endpoint. At 6 months, xerostomia rates using salivary scintigraphy were 14% (5/35: 95% CI, 5%-30%) in the BT arm while it was seen in 44% (14/32: 95% CI, 26%-62%) in the IMRT arm (P = .008). Physician-rated Radiation Therapy Oncology Group grade ≥2 xerostomia at any time point was observed in 30% of patients (9/30) in the IMRT arm and 6.7% (2/30) in the BT arm (P = .02). At a median follow-up of 42.5 months, the 3-year local control in the IMRT arm was 56.4% (95% CI, 43%-73%) while it was 66.2% (95% CI, 53%-82%) in the BT arm (P = .24). CONCLUSIONS: The addition of BT to IMRT for T1-T2N0M0 OPSCC results in a significant reduction in xerostomia. This strongly supports the addition of BT to IMRT in suitable cases.

Response assessment of post-treatment head and neck cancers to determine further management using NI-RADS (Neck Imaging Reporting and Data System): a subgroup analysis of a randomized controlled trial.

Objective: Interpreting complex post-treatment changes in head and neck cancer (HNC) is challenging with further added perplexity due to variable interobserver interpretation and hence evolved the NI-RADS lexicon. We evaluated the accuracy of NI-RADS in predicting disease status on 1st post-treatment follow-up CECT in a homogenous cohort of those who received only chemoradiation. Methods: Retrospective analysis of imaging was done for LASHNC patients who received radical chemoradiation in an open-label, investigator-initiated, phase 3 randomized trial (2012-2018) randomly assigned to either radical radiotherapy with concurrent weekly cisplatin (CRT) or CRT with the same schedule plus weekly nimotuzumab (NCRT). 536 patients were accrued, and 74 patients who did not undergo PET/CECT after 8 weeks post-CRT were excluded. After assessing 462 patients for eligibility to allocate NI-RADS at primary and node sites, 435 cases fell in the Primary disease cohort and 412 cases in the Node disease cohort. We evaluated sensitivity, disease prevalence, the positive and negative predictive value of the NI-RADS lexicon, and accuracy, which were expressed as percentages. We also prepared flow charts to determine concordance with allocated NI-RADS category and established accuracy with which it can identify disease status. Results: Out of 435 primary disease cohort, 92%, 55%, 48%,70% were concordant and had 100%, 72%, 70%, 82% accuracy in NI-RADS1 (n=12), NI-RADS2 (n=261), NIRADS3 (n=105), and NI-RADS 4 (n=60) respectively. Out of 412 nodes disease cohort, 95%, 90%, 48%, 70%were concordant and had 92%, 97%, 90%, 67% accuracy in NI-RADS1 (n=57), NI-RADS2 (n=255), NI-RADS3 (n=105) and NI-RADS4 (n=60) respectively. % concordance of PET/CT and CECT across all primary and node disease cohorts revealed that PET/CT was 91% concordant in primary NI-RADS2 as compared to 55% concordance of CECT whereas concordance of CECT was better with 57% in primary NI-RADS3 cohort as compared to PET/CT concordance of 41%. Conclusion: The accuracy with which the NI-RADS lexicon performed in our study at node sites was better than that at the primary site. There is a great scope of research to understand if CECT performs better over clinical disease status in NI-RADS 3 and 4 categories. Further research should be carried out to understand if PET/CECT can be used for close interval follow-up in stage III/IV NI-RADS 2 cases.

Transitioning India to advanced image based adaptive brachytherapy: a national impact analysis of upgrading National Cancer Grid cervix cancer guidelines.

Background: High-dose-rate image guided brachytherapy (IGBT) for cervical cancer leads to improved local control and reduced toxicity and is a critical component of treatment. However, transition to IGBT requires capacity upscaling. An institutional activity mapping and national impact analysis of such a transition were undertaken to understand feasibility. Methods: Between September 2020 and March 2021, activity mapping was conducted in a high-volume centre that triaged cervical cancer patients for brachytherapy into four workflows; A: two-dimensional (2D) X-Ray point A-based intracavitary brachytherapy, B: CT point A-based intracavitary brachytherapy, C: MRI/CT-volume based intracavitary brachytherapy, D: MRI/CT volume-based intracavitary +/- interstitial brachytherapy. Clinical process time mapping was performed, and case scenarios for transition were modelled at the institutional and national levels based on available incidence and infrastructure levels. Treatment capacity changes were calculated, and potential strategies for workflow reorganisation were proposed. Findings: Eighty-four patients were included in the study. The total time taken for the workflows A, B, C, and D were 176 min (57-208), 224 min (74-260), 267 min (101-302), and 348 min (232-383), respectively. The transition from workflow A to D through sequential steps led to 35%, 49%, and 64% loss of treatment capacity in the index institution. Solutions such as 10-hour or 12-hour overlapping shifts increased treatment capacity by 25% and 50% and performing single implants and delivering multiple fractions increased capacity by 100%. Twenty-three Indian states and Union Territories are predicted to be able to transition to advanced workflows. For four Indian states, it may be detrimental considering the current infrastructure level, and eight Indian states lacked brachytherapy access. Further financial investment is required in the latter 12 states for transition to advanced workflows. Interpretation: Our study demonstrates that unplanned transition to IGBT can lead to treatment capacity loss and increase in waiting lists to access treatment. The proposed solutions of workflow reorganisation, using strategies such as single brachytherapy applicator implant and delivering multiple treatment fractions can improve access to treatment for women with cervix cancer in resource-strained and high patient-volume settings. We recommend state-wise solutions for the upscale from conventional 2D workflows to IGBT, subject to the availability of skilled personnel, infrastructure and training. Financial investments may be needed in some states to achieve this goal. Funding: International Atomic Energy Agency (IAEA) supported the salary of VH through project E33042 that focussed on implementation strategies of image guided brachytherapy.

Computerized tomography-based first order tumor texture features in non-small cell lung carcinoma treated with concurrent chemoradiation: A simplistic and potential surrogate imaging marker for survival.

Objectives: This study examines the role of tumor texture on computed tomography (CT) images as a complement to clinical prognostic factors in predicting survival in patients of non-small cell lung carcinoma (NSCLC) treated with radical chemo-radiation (CRT). Methods: A total of 93 patients with confirmed NSCLC treated with CRT accrued in a study approved by the institutional ethics committee were analyzed for CT-based radiomic features. Pretreatment CT images were used to contour the primary tumor and texture features were computed by the image filtration method to differentially highlight fine to coarse textures. Texture parameters included mean intensity, entropy, kurtosis, standard deviation, and mean positive pixel and skewness. Optimal threshold cut-off values of the above tumor texture features were analyzed. These features were explored as imaging biomarkers to predict survival using Kaplan-Meier and Cox proportional hazard model. Results: Median follow-up of the entire cohort was 23.5 months [Interquartile range, IQR: 14-37] while for alive patients, median follow-up was 31 months (IQR: 23-49), 47 (50.6%) patients had died at the last follow-up. Univariate analysis revealed certain features like age, gender, response to therapy, and texture features like mean and kurtosis in CT images to be significant predictors of survival. In multivariate analysis, age (P = 0.006), gender (P = 0.004), treatment response (P< 0.0001), and two CT texture parameters: mean (P = 0.027) and kurtosis (P= 0.002) were independent prognostic factors of survival. Interpretation and Conclusion: CT-derived tumor heterogeneity (mean and kurtosis) complements clinical factors for predicting survival in NSCLC patients treated with CRT. Tumor radiomics warrants further validation as potential prognostic biomarkers for these patients.

Machine-Learning-Based Radiomics for Classifying Glioma Grade from Magnetic Resonance Images of the Brain.

Grading of gliomas is a piece of critical information related to prognosis and survival. Classifying glioma grade by semantic radiological features is subjective, requires multiple MRI sequences, is quite complex and clinically demanding, and can very often result in erroneous radiological diagnosis. We used a radiomics approach with machine learning classifiers to determine the grade of gliomas. Eighty-three patients with histopathologically proven gliomas underwent MRI of the brain. Whenever available, immunohistochemistry was additionally used to augment the histopathological diagnosis. Segmentation was performed manually on the T2W MR sequence using the TexRad texture analysis softwareTM, Version 3.10. Forty-two radiomics features, which included first-order features and shape features, were derived and compared between high-grade and low-grade gliomas. Features were selected by recursive feature elimination using a random forest algorithm method. The classification performance of the models was measured using accuracy, precision, recall, f1 score, and area under the curve (AUC) of the receiver operating characteristic curve. A 10-fold cross-validation was adopted to separate the training and the test data. The selected features were used to build five classifier models: support vector machine, random forest, gradient boost, naive Bayes, and AdaBoost classifiers. The random forest model performed the best, achieving an AUC of 0.81, an accuracy of 0.83, f1 score of 0.88, a recall of 0.93, and a precision of 0.85 for the test cohort. The results suggest that machine-learning-based radiomics features extracted from multiparametric MRI images can provide a non-invasive method for predicting glioma grades preoperatively. In the present study, we extracted the radiomics features from a single cross-sectional image of the T2W MRI sequence and utilized these features to build a fairly robust model to classify low-grade gliomas from high-grade gliomas (grade 4 gliomas).

Brachytherapy training in India: Results from the GEC-ESTRO-India survey.

INTRODUCTION: Brachytherapy (BT) is integral in treatment of gynecological malignancies and is also an option for many other cancers. Data on training and proficiency levels of early career oncologists is limited. Like other continents a survey was conducted for early career oncologists in India. METHODS AND MATERIALS: An online survey was conducted from November 2019 to February 2020, through Association of Radiation Oncologists of India (AROI) for early career radiation oncologists expected to be within 6 years of training. The survey used a 22 item questionnaire that was also used for European survey. Responses to individual statements were recorded on a 1-5 Likert-type scale. Descriptive statistics were used to describe proportions. RESULTS: One-hundred twenty-four (17%) of 700 recipients responded to the survey. Majority of the respondents (88%) stated that being able to perform BT at the end of their training was important. Two-thirds of the respondents (81/124) had performed >10 intracavitary procedure and 22.5% had performed >10 intracavitary-interstitial implants. Many respondents had not performed nongynecological procedure- breast (64%), prostate(82%), gastro-intestinal (47%). Respondents predicted that in next 10 years, the role of BT is likely to increase. Lack of dedicated curriculum and training was perceived as the greatest barriers to achieving independence in BT (58%). Respondents suggested that BT training should be prioritized during conferences (73%) and online teaching modules (56%), along with development of BT skills labs (65%). CONCLUSION: This survey identified a lack of proficiency in gynecological intracavitary-interstitial brachytherapy and non-gynecological brachytherapy, despite BT training being regarded as highly important. Dedicated programs, including standardized curriculum and assessment need to be developed for training early- career radiation oncologists in BT.

Diagnostic Performance of Response Assessment FDG-PET/CECT in HNSCC Treated With Definitive Radio(chemo)therapy Using NI-RADS.

OBJECTIVE: To assess the diagnostic performance of response assessment 18F-fluorodeoxyglucose positron emission tomography/contrast-enhanced computed tomography (FDG-PET/CECT) following definitive radio(chemo)therapy in head and neck squamous cell carcinoma (HNSCC) using Neck Imaging Reporting and Data System (NI-RADS). STUDY DESIGN: A retrospective analysis from a prospectively maintained dataset. SETTING: Tertiary-care comprehensive cancer center in a low-middle-income country. METHODS: Adults with newly diagnosed, biopsy-proven, nonmetastatic HNSCC treated with definitive radio(chemo)therapy were included. Posttreatment response assessment FDG-PET/CECT scans were retrospectively assigned NI-RADS categories (1-3) for the primary site, neck, and both sites combined. Locoregional recurrence occurring within 2-years was defined as the event of interest. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and overall accuracy were calculated. Locoregional control stratified by NI-RADS categories was computed with the Kaplan-Meier method and compared using the log-rank test. RESULTS: Posttreatment FDG-PET/CECT scans were available in 190 patients constituting the present study cohort. Sensitivity, specificity, PPV, NPV, and overall accuracy of the NI-RADS template for the primary site was 73.5%, 81.4%, 46.3%, 93.4%, and 80.0%, respectively. Similar metrics for the neck were 72.7%, 87.5%, 43.2%, 96.1%, and 85.8%, respectively. Combining primary site and neck, the corresponding metrics of diagnostic accuracy were 84.4%, 69.7%, 46.3%, 93.5%, and 73.2%, respectively. At a median follow-up of 40 months, Kaplan-Meier estimates of 2-year locoregional control were significantly higher for NI-RADS category 1 (94.2%) compared to NI-RADS category 2 (69.4%) and category 3 (20.4%), respectively (stratified log-rank p < .0001). CONCLUSION: FDG-PET/CECT using the NI-RADS template is associated with good diagnostic performance and prognostic utility in HNSCC treated with definitive radio(chemo)therapy.

Prophylactic versus reactive feeding approach in patients undergoing adjuvant radiation therapy for oral cavity squamous cell carcinoma: A propensity score matched-pair analysis.

BACKGROUND: To assess the efficacy of prophylactic versus reactive feeding strategy in oral cavity squamous cell carcinoma (OCSCC) patients receiving adjuvant radiation therapy (RT). METHODS: This was a post hoc analysis of patients of OCSCC enrolled in a randomized trial comparing three adjuvant strategies. In this trial, till 2010, a prophylactic feeding approach was followed for all patients. Since January 2011, a reactive feeding approach was followed. RESULTS: Two hundred and sixty-eight in each cohort (total n = 526) were eligible for analysis after propensity score matching. At 6 weeks post-RT completion, the median weight loss in the prophylactic versus reactive cohort was 5 versus 3 kg, p = 0.002. At all other time points until 1 year, the median weight loss was lesser in reactive than in the prophylactic cohort. CONCLUSIONS: A reactive feeding tube approach should be preferred for OCSCC receiving adjuvant RT.

Clinical management of stage III non-small cell lung cancer in India: An expert consensus statement.

Non-small cell lung cancer (NSCLC) is considered the most common type of lung cancer (>80% of all lung cancers); patients are often diagnosed at advanced stages of the disease. The management of NSCLC is considered challenging owing to variations in size, an extension of the tumors, involvement patterns, and classification. Although adequate literature and guidelines are available on the management of NSCLC in several countries, an Indian perspective on stage III NSCLC management is lacking. We used the modified Delphi approach to form consensus statements. A thorough literature search was done. The authors then convened and deliberated over published literature, available guidelines, and clinical judgment. Recommendation statements were formed for different clinical scenarios. These statements were sent as a form of survey to other oncologists, and their responses were recorded and mentioned. Evidence-based statements were formed for diagnosing and managing stage III NSCLC. These recommendation statements cover various aspects-surgical, radiation, and medical treatment in various clinical scenarios including adjuvant, neoadjuvant, and consolidation therapies.

Image-guidance triggered adaptive radiation therapy in head and neck squamous cell carcinoma: single-institution experience and implications for clinical practice.

PURPOSE: To report frequency and timing of adaptive radiotherapy (ART) and assess patient, disease, and treatment-related characteristics potentially triggering the need for such adaptive replanning in head and neck squamous cell carcinoma (HNSCC). METHODS: Medical records of HNSCC patients treated with definitive intensity modulated radiation therapy (IMRT) with or without concurrent systemic chemotherapy were reviewed retrospectively to identify patients undergoing image-guidance triggered adaptive replanning. Clinico-demographic characteristics of patients undergoing ART were compared with patients treated without adaptation using the chi-square test. RESULTS: Two hundred patients with squamous cell cancers of the oropharynx, larynx, or hypopharynx treated with definitive IMRT between 2014 to 2019 comprised the study cohort. Twenty-seven (13.5%) patients underwent adaptive replanning during treatment at a median of 17 fractions (inter-quartile range 14-24 fractions). There were no significant differences in the baseline patient (age, gender), disease (site of primary, staging/grouping), and treatment-related characteristics (dose-fractionation, chemotherapy usage) in patients undergoing ART compared to those treated without adaptation. Weight loss during IMRT emerged as a significant factor predicting the need for ART; patients having ≥10% weight loss from baseline were more likely to undergo treatment adaptation compared to patients with <10% weight loss (p = 0.0002). There was variable impact of ART on dose-volume statistics of organs-at-risk such parotid glands and spinal cord. CONCLUSION: Image-guidance triggered ART for HNSCC is not associated with significant improvement in OAR dosimetry. However, weight loss during definitive IMRT can be a potentially useful trigger for identifying patients who are most likely to benefit from such adaptive replanning.

Early outcomes of abbreviated multi-fractionated brachytherapy schedule for cervix cancer during COVID-19 pandemic.

PURPOSE: Brachytherapy (BT) for cervix cancer was listed as a level I priority and reduced number of implants and multiple fractions were recommended during COVID-19 pandemic. We present early clinical outcome of this approach. METHODS AND MATERIALS: Patients treated with (chemo)radiotherapy and BT with single implant and multiple fractions BT were included. Treatment protocol included 3-5 fractions of 5-8.5 Gy with an aim to achieve point A dose of 70 Gy EQD210Gy (or HRCTV dose of >80 Gy EQD210Gy) in those undergoing intracavitary (IC) and HRCTV dose >85 Gy EQD2 10Gy in patients undergoing Intracavitary-Interstitial (IC/IS) whereas maintaining bladder (B2cc), rectum (R2cc), sigmoid (S 2cc) doses of 90, 75, and 75 Gy EQD23Gy. Time to event analysis was used to report oncological endpoints. Toxicity was reported using crude proportions. RESULTS: From April 2020 to March, 2021, 64 patients with stage IB2-IV received single implant and multi-fraction BT after external radiation of 45 Gy/25 fractions/5 weeks. Only 76.7% (n = 49) received concurrent chemotherapy. Median overall treatment time (OTT) was 56 days (38-131 days). Overall, 62.5% (n = 40) patients received IC and 37.5% (n = 24) received IC+IS. The median HRCTV was 34.7 cc (IQR 25-41). Median (IQR) point A dose, HRCTV D90, B2cc, R2cc, and S2cc for those undergoing IC was 74 Gy (71-78), 80 Gy (73-84), 86 Gy (82-89), 70 Gy (65-74), 65 Gy (59-73) respectively. For the IC+IS cohort, HRCTV D90, B2cc, R2cc, and S2cc was 84 Gy (78-89 Gy), 89 Gy (86-92), 70 Gy (67-74), 68 Gy (59-76). At a median follow-up of 16 months (5-27) the 2-year local control, pelvic control, cause specific and overall survival was 88%, 85.3%, 92.2%, and 81.3% respectively. Late gastrointestinal and genitourinary grade ≥III toxicities were 14% and 1.5% each. CONCLUSIONS: Abbreviated BT outcomes are encouraging for oncological outcomes despite delays in overall treatment time and omission of chemotherapy. Further mature follow up is needed.

Practice Patterns and Perspectives on Stereotactic Body Radiation Therapy for the Metastatic Spine From Lower- and Middle-Income Countries.

PURPOSE: We wanted to understand the current practice patterns and stereotactic body radiation therapy (SBRT) utilization for spine metastases in lower- and middle-income countries (LMICs). METHODS: A questionnaire was designed to identify the current practice patterns of treating spine metastases, uptake of spine SBRT in routine care, dose fractionations commonly used, and the perceived benefits and toxicities of using ablative doses. Individuals registering for a spine SBRT workshop were requested to answer the questionnaire. RESULTS: We received 395 responses from radiation oncologists (ROs) working in 12 different LMICs. The majority of respondents were from an academic institute (57.5%). Two hundred seventy-four respondents further identified themselves from the government/public sector (44.89%), corporate/private sector (47.89%), not-for-profit organization (5.4%), or public-private partnership (5.4%). The respondents indicated that 8.43%, 27.46%, 41.73%, and 10.04% of the spine metastases patients are treated using clinical marking, X-ray-based, 3D conformal radiation therapy, and SBRT, respectively. A third of the respondents did not have any experience of spine SBRT; those with high-volume practice were predominantly from an academic institute. The majority of respondents would use spine SBRT to reduce pain severity (71.9%) and achieve durable pain control (61.01%) in the setting of oligometastases (92.73%) and reirradiation (56.69%). Respondents preferred 3- to 5-fraction regimens (64.9%) over 1-2 fractions (33.68%). The top three reasons for not using spine SBRT were resource constraints (50%), lack of machine (37.11%), and lack of training (27.34%). CONCLUSION: There is heterogeneity in spine SBRT practice and utilization between academic and nonacademic institutes. Resource and infrastructure constraints along with lack of training are limiting the use of SBRT among ROs from LMICs. Collaborative studies from LMICs will help in resolving unique challenges posed by resource constraints.

Concurrent chemoradiotherapy with cisplatin given once-a-week versus every-three weekly in head and neck squamous cell carcinoma: Non-inferior, equivalent, or superior?

Cisplatin-based concurrent chemoradiotherapy is the contemporary standard-of-care in curative-intent management of loco-regionally advanced head and neck squamous cell carcinoma. The most optimal dose-schedule of concurrent cisplatin remains debatable with widespread variability in clinical practice. High-quality evidence in favour of cisplatin-based chemoradiotherapy is largely based on high-dose cisplatin given as 100 mg/m2 every three-weekly for up to three cycles. However, such dosing is typically associated with high rates of significant acute hematological and renal toxicity prompting the need for alternative lesser toxic dose-schedules. Compliance to three doses of three-weekly high-dose cisplatin is reportedly suboptimal with nearly 40% of patients unable to receive the third cycle thereby achieving cumulative cisplatin dose of 200 mg/m2 which is generally regarded sufficient for beneficial anti-tumor effect. The most common alternative schedule is low-dose (20-50 mg/m2) cisplatin once-weekly during radiotherapy. Such low-dose weekly regimens have undergone less rigorous prospective evaluation versus RT alone but continue to be widely used in co-operative group trials and routine clinical practice. In the last decade, several small prospective randomized controlled trials have reported significantly lesser toxicity and comparable disease-related outcomes with low-dose weekly cisplatin. However, two recent randomized controlled trials have re-ignited the debate globally due to their contradictory results, inferences, and conclusions. Through this commentary, we critically appraise and summarize the existing evidence-base to inform contemporary clinical practice and guide future research. There is increasingly emerging evidence that chemoradiotherapy with once-weekly cisplatin is non-inferior to three-weekly cisplatin for disease-related outcomes in curative-intent management of loco-regionally advanced head and neck cancer.

Access to Radiation Therapy: From Local to Global and Equality to Equity.

The discipline of radiation oncology is the most resource-intensive component of comprehensive cancer care because of significant initial investments required for machines, the requirement of dedicated construction, a multifaceted workforce, and recurring maintenance costs. This review focuses on the challenges associated with accessible and affordable radiation therapy (RT) across the globe and the possible solutions to improve the current scenario. Most common cancers globally, including breast, prostate, head and neck, and cervical cancers, have a RT utilization rate of > 50%. The estimated annual incidence of cancer is 19,292,789 for 2020, with > 70% occurring in low-income countries and low-middle-income countries. There are approximately 14,000 teletherapy machines globally. However, the distribution of these machines is distinctly nonuniform, with low-income countries and low-middle-income countries having access to < 10% of the global teletherapy machines. The Directory of Radiotherapy Centres enlists 3,318 brachytherapy facilities. Most countries with a high incidence of cervical cancer have a deficit in brachytherapy facilities, although formal estimates for the same are not available. The deficit in simulators, radiation oncologists, and medical physicists is even more challenging to quantify; however, the inequitable distribution is indisputable. Measures to ensure equitable access to RT include identifying problems specific to region/country, adopting indigenous technology, encouraging public-private partnership, relaxing custom duties on RT equipment, global/cross-country collaboration, and quality human resources training. Innovative research focusing on the most prevalent cancers aiming to make RT utilization more cost-effective while maintaining efficacy will further bridge the gap.

Small cell carcinoma of the oesophagus: experience of an Indian Tertiary Cancer Centre.

Introduction: Small cell carcinoma of the oesophagus (SCCE) is a rare and aggressive tumour with no established standard treatment. Methods: This is a retrospective study of adult patients with histologically proven SCCE registered between February 2011 and March 2020 at Tata Memorial Hospital in Mumbai. Results: There were 56 patients, with 29 (51.8%) having limited-stage disease (LD) and 27 (48.2%) having extensive-stage disease (ED). The median age was 58 (interquartile range = 51-65) years; 57.1% were men; and 40% were smokers. Among LD-SCCE patients, 23 underwent local therapy, i.e., radiation (19, 65.5%) and surgery (4, 13.8%), and 27 received chemotherapy in neoadjuvant (23, 79.3%), concurrent (18, 62.1%) and adjuvant (4, 13.8%) settings. Totally, 19 ED-SCCE patients (70.4%) received chemotherapy. Prophylactic cranial irradiation (PCI) was delivered to 11 (37.9%) and 7 (25.9%) patients with LD-SCCE and ED-SCCE, respectively. Significant grade 3 or more chemotoxicities in patients with LD-SCCE and ED-SCCE included febrile neutropenia in 33.3% and 23.5%, anaemia in 9.5% and 17.6%, and dyselectrolytemia in 14.3% and 11.8%, respectively. The median overall survival (OS) in LD-SCCE and ED-SCCE was 22.9 (95% CI = 1.8-44.1) months and 11.8 (95% CI = 7.3-16.4) months, respectively. Age <60 years (p = 0.004) and tumour epicentre in the lower third oesophagus (p = 0.002) were independent good prognostic factors for OS in LD-SCCE and ED-SCCE patients, respectively. The incidence of brain metastasis was low, at both presentation (1/27, 3.7%) and relapse (5/56, 8.9%). Conclusion: Although the survival of LD-SCCE is better than ED-SCCE, it is still under 2 years. Brain metastases are uncommon and the role of PCI is uncertain.

Impact of the First Wave of COVID-19 Pandemic on Radiotherapy Practice at Tata Memorial Centre, Mumbai: A Longitudinal Cohort Study.

PURPOSE: Delivery of cancer care during the pandemic required adopting various changes in the standard management. We analyzed the impact of the first wave of the COVID-19 pandemic on radiation oncology treatment practices at Tata Memorial Hospital in India. MATERIALS AND METHODS: From March 1 to October 31, 2020, all consecutive patients who attended the radiation oncology department for radiotherapy treatment were included in this study. Electronic medical records, patient files, and telephonic consult were used to collect patient's data including changes in the standard treatment practice, COVID-19 testing and its results, and subsequent impact on radiotherapy treatment. Comparison was done with the same period data of 2019 for the number of the caseload, radiotherapy regimen, referral rates, and noncompliance rates. RESULTS: Our study included 4,256 patients with a median age of 52 years (interquartile range 41-61 years). There was a significant drop in the new-patient registrations (approximately 63%), radiotherapy consultations (44.9%), and referrals to other centers (27.8%). The reduction in the caseload was highest for genitourinary cases (-58.5%) and the lowest for breast cases (-11.5%) when compared with the 2019 cohort. Among those treated with radical intent, the noncompliance rate was 15%. Hypofractionation was the commonly adopted regimen across all sites. Compared with 2019, the maximum reduction in the average fractions per patient was seen in the breast cancer cases (-8.2 fraction), followed by genitourinary cases (-4.9 fraction). Of the 27.8% of patients tested for COVID-19, 13.4% turned positive and 3.4% died due to the disease. CONCLUSION: The COVID-19 pandemic adversely affected the number of radiotherapy consultations and treatments at our institute. However, our department offered uninterrupted services despite grave challenges. Hypofractionated regimen was used across disease sites to minimize patient visits and allow planned treatment completion. Radiotherapy was delivered safely, and patients experienced low rates of COVID positivity during radiotherapy and even lower mortality.