Predictors of Occult Neck Metastasis and Extra Capsular Spread in Early Oral Cancers.

To investigate the incidence of occult neck metastasis and to determine the prognostic factors related to the occurrence of the cervical lymph nodal metastasis and extra capsular extension (ECE) in early oral cavity cancer patients. A retrospective review performed on 100 patients with node negative squamous cell carcinoma of oral cavity who underwent primary treatment between Jan 2015 and Dec 2018. Incidence of occult neck metastasis after the elective neck dissection in our study was 35%. Independent correlates of positive occult neck metastasis were lymphovascular Invasion (P-0.000)[CI 0.004-0.326] and depth of invasion(P-0.009)[CI 0.509-13.428] on univariate analysis and statistically significant factors associated with the incidence of the extracapsular extension were age(P-0.044), lymphovascular invasion(P-0.018)[CI 0.004-0.603] and lymph node ratio(P-0.000)[CI 4.570-158.45] on univariate analysis. Lymphovascular invasion and depth of invasion correlated significantly with occurrence of neck metastasis. Age and LVI were the prognostic factors for extra capsular spread.

Medulloblastoma outcomes in tertiary care set-up in India using contemporary treatment protocols - A retrospective study.

Background: Medulloblastoma is the commonest embryonal brain tumor in children. It has shown improved outcomes with combined modality treatment. We aimed to study patient characteristics and survival outcomes of patients with this disease across two tertiary care centers in India. Methods: We analyzed data of patients with histological diagnosis of medulloblastoma treated from January 2010 to January 2016. Patient characteristics and follow-up data were retrieved from hospital records. Descriptive statistics were used to describe clinical and pathological characteristics. Overall survival (OS) was calculated from date of diagnosis to death due to any cause. Relapse-free survival (RFS) was calculated from date of diagnosis to occurrence of relapse or death. Result: Out of 26 patients treated, 24 were children and 2 were adults. Median age was 10 years (range = 0.8-22 years). Twenty (76.9%) patients were male. Fifteen (57.7%) patients were stratified as high-risk (HR), rest 11 (42.3%) were categorized as average risk (AR). Histopathology showed classical variety in majority of patients except for 4 (15%) cases, 3 with desmoplastic and 1 with anaplastic subtype. Median follow-up was 49.7 months (range= 4.2-102.5 months). Overall, eight (30.8%) patients relapsed and six (23%) deaths occurred. Five (33.3%) patients in HR category and 3 (27.3%) patients in AR group showed relapse. Median RFS and OS were not yet reached. Five-year RFS was 69.2% whereas five-year OS was 76.9%. Conclusion: This study highlighted patient characteristics and treatment outcomes in Indian patients. With adherence to standard treatment, high remission rates and improvement in mortality rates were achieved.

Deviation from delivery of radiation therapy to childhood cancer patients: A retrospective audit.

BACKGROUND: Planning and coordination of the delivery of radiation therapy (RT) can be challenging in resource-limited settings. In this retrospective study, we describe the profile of children undergoing radiation and analyze deviation from some accepted norms. PROCEDURE: Data on all children (<18 years of age) with cancer who completed RT from January 2009 to December 2019 were retrieved. Diagnostic groups with more than five patients were included in the analysis for deviations in RT (time to start [TTS]; total dose delivered [TDD] in gray; and time to complete [TTC]). We investigated reasons for deviation. RESULTS: Two hundred seven children received RT as front-line treatment (68% Indian, 59% male). Most common diagnoses were brain tumors (44%), lymphomas (13%), leukemias, and soft tissue sarcomas (10% each). TTS deviation was seen in 23.6%, TTD in 6.0%, and TTC in 24.7%, while 43.4% had at least one deviation in any of these three parameters. Deviation in TTS varied significantly by location of preceding treatment and by cancer (greatest deviation in sarcomas), with issues around access to health care being the most common reason. Deviation in TTC varied significantly by cancer (greatest deviation in sarcomas and medulloblastoma), with myelotoxicity being the most common reason. CONCLUSIONS: Our study adds to the limited literature on RT quality for children with cancer in resource-limited settings. Certain cancers (sarcomas and medulloblastomas) and patient groups (preceding treatment outside our institute) had the maximum deviation. Barriers to accessing care and myelotoxicity were the two main reasons for this deviation.

Real-World Experience of Immunotherapy from India in Recurrent Squamous Cell Carcinoma of Head and Neck Cancer.

Background Recurrent metastatic head and neck squamous cell carcinoma (HNSCC) patients carry a poor prognosis and have limited therapeutic options. In the randomized phase-3 trial CheckMate 141, nivolumab showed benefit in overall survival (OS) with manageable toxicity. Nivolumab is available for clinical practice since 2017 in India. The aim of this study is to evaluate the efficacy and safety of nivolumab in real-world settings in India. Materials and Methods This is a retrospective, single-center study on the use of nivolumab with advanced or metastatic HNSCC in India. Eligible patients had histologically confirmed, recurrent squamous cell carcinoma of the head and neck (including metastatic disease) of the oral cavity, pharynx, or larynx that was not amenable to curative treatment, tumor progression, or recurrence after the administration of platinum-containing chemotherapy administered as adjuvant therapy or in the context of primary or recurrent disease. We assessed demographics, safety (the Common Terminology Criteria for Adverse Events Version 4.0), response evaluation (the Response Evaluation Criteria in Solid Tumors Version 1.1), progression-free survival (PFS), and OS. Results Among patients with platinum-refractory, recurrent HNSCC, and treatment with nivolumab resulted in median PFS of 2 months and median OS of 5 months, which is inferior to what was seen in CheckMate 141. Fifteen of 20 patients (75%) had progressive disease, 3 (15%) showed a partial response, and 2 (10%) had stable disease. Conclusion Nivolumab was well tolerated in our study with fewer toxic effects, and an inferior median survival was reached as compared with CheckMate 141 in platinum refractory, recurrent HNSCC patients treated with nivolumab because 90% of patients in our study received nivolumab as second-line therapy after progression. Our study encourages the use of nivolumab in this population.

Impact of COVID-19 on cancer care in India: a cohort study.

BACKGROUND: The COVID-19 pandemic has disrupted health-care systems, leading to concerns about its subsequent impact on non-COVID disease conditions. The diagnosis and management of cancer is time sensitive and is likely to be substantially affected by these disruptions. We aimed to assess the impact of the COVID-19 pandemic on cancer care in India. METHODS: We did an ambidirectional cohort study at 41 cancer centres across India that were members of the National Cancer Grid of India to compare provision of oncology services between March 1 and May 31, 2020, with the same time period in 2019. We collected data on new patient registrations, number of patients visiting outpatient clinics, hospital admissions, day care admissions for chemotherapy, minor and major surgeries, patients accessing radiotherapy, diagnostic tests done (pathology reports, CT scans, MRI scans), and palliative care referrals. We also obtained estimates from participating centres on cancer screening, research, and educational activities (teaching of postgraduate students and trainees). We calculated proportional reductions in the provision of oncology services in 2020, compared with 2019. FINDINGS: Between March 1 and May 31, 2020, the number of new patients registered decreased from 112 270 to 51 760 (54% reduction), patients who had follow-up visits decreased from 634 745 to 340 984 (46% reduction), hospital admissions decreased from 88 801 to 56 885 (36% reduction), outpatient chemotherapy decreased from 173634 to 109 107 (37% reduction), the number of major surgeries decreased from 17 120 to 8677 (49% reduction), minor surgeries from 18 004 to 8630 (52% reduction), patients accessing radiotherapy from 51 142 to 39 365 (23% reduction), pathological diagnostic tests from 398 373 to 246 616 (38% reduction), number of radiological diagnostic tests from 93 449 to 53 560 (43% reduction), and palliative care referrals from 19 474 to 13 890 (29% reduction). These reductions were even more marked between April and May, 2020. Cancer screening was stopped completely or was functioning at less than 25% of usual capacity at more than 70% of centres during these months. Reductions in the provision of oncology services were higher for centres in tier 1 cities (larger cities) than tier 2 and 3 cities (smaller cities). INTERPRETATION: The COVID-19 pandemic has had considerable impact on the delivery of oncology services in India. The long-term impact of cessation of cancer screening and delayed hospital visits on cancer stage migration and outcomes are likely to be substantial. FUNDING: None. TRANSLATION: For the Hindi translation of the abstract see Supplementary Materials section.

Adapting Management of Sarcomas in COVID-19: An Evidence-Based Review.

With the novel coronavirus disease (COVID-19) being declared a global pandemic by the World Health Organization, the Indian healthcare sector is at the forefront to deliver optimal care. Patients with cancer especially are at serious risk for increased chances of morbidity and mortality due to their immunocompromised state. Currently there is a paucity of definitive guidelines for the management of sarcomas during the pandemic in a resource-constrained and diverse population setting like India. Health care professionals from various specialties involved in the management of sarcomas have collaborated to discuss various aspects of evidence-based sarcoma management during the COVID-19 pandemic. This article provides structured recommendations for HCP to adapt to the situation, optimize treatment protocols with judicious use of all resources while providing evidence-based treatment for sarcoma patients.

Dosimetric Comparison of Different Planning Techniques in Left-sided Whole-Breast Irradiation: A Planning Study.

PURPOSE: This planning study compared the various dosimetric parameters of different types of intensity-modulated radiotherapy (IMRT) and volumetric-modulated arc therapy (VMAT) techniques for left-sided breast cancer radiotherapy. MATERIALS AND METHODS: Treatment of 22 left-sided breast cases was planned using two IMRT and VMAT techniques for the prescription of 40 Gy in 15 fractions. For tangential IMRT (Tan_IMRT), five beams were placed as conventional tangential beams. For equally spaced IMRT (Equi_IMRT), six beams were placed equidistantly at 40° interval from 300° to 140°. For tangential VMAT (Tan_VMAT), two arcs were used with the avoidance sector in such a way that the beam covered like tangential fields. For full-arc VMAT (Full_VMAT), similar arcs as Tan_VMAT were used, without avoidance sector. All treatment plans were generated using Eclipse planning system for TrueBeam STx linear accelerator. For planning target volume (PTV), dose parameters including D95%, D99%, V105% homogeneity index (HI), and conformity index (CI) were analyzed. Different dose parameters for the left lung, heart, left anterior descending artery (LAD), right lung, and right breast were also analyzed. In addition, low-dose spillage in the normal tissues and the number of monitor units (MUs) required for the treatment were compared. RESULTS: IMRT technique exhibited superior D95% and D99% for PTV compared with VMAT techniques. VMAT plans provided more V105% (6%) compared with that of IMRT plans (approximately 1%). HI was better in IMRT plans (Tan_IMRT, 0.085 ± 0.015; Equi_IMRT, 0.094 ± 0.011) than in VMAT plans. CI was better in VMAT plans. The mean lung dose (7.7 Gy ± 1.788 Gy) and V5Gy (34.99% ± 6.799%) were better achieved in Tan_IMRT plan than other plans. Right lung, heart, and right breast sparing were better achieved in Tan_IMRT plan. Moreover, low-dose spillage was very less in the Tan_IMRT compared with all other techniques. CONCLUSION: Dosimetric comparison in this study showed that tangential IMRT technique is superior in terms of target coverage, sparing of lung, heart, and right breast, and low-dose spillage control in the left-sided breast-only radiotherapy.

Harnessing the Immunomodulatory Effects of Radiation in Urinary Bladder Cancer.

The use of local radiation to elicit distant tumor response was proposed long back. The abscopal effect is regression of non-irradiated metastatic lesions at the distant site and there is an enormous therapeutic effect of immunomodulation. Radiation causes cancer cells to release antigens which mount an immune response, but this response is short lasting because cancer cells evade recognition by different mechanisms. Programmed Death Ligand-1 (PDL-1) pathway has been extensively studied. Combining immunotherapy and radiotherapy may result in long-term remissions especially for stage 4 cancer. Here we present a case of high grade urothelial carcinoma that progressed after four cycles of chemotherapy and after giving palliative radiation to urinary bladder he was started on nivolumab. First scan done after radiation and six cycles of nivolumab showed complete response. The patient continues to be in remission for the last 17 months from the start of radiation and immunotherapy that was started sequentially. Overall survival till date is 25 months.

Significance of perineural invasion in locally advanced bucco alveolar complex carcinomas treated with surgery and postoperative radiation ± concurrent chemotherapy.

BACKGROUND: The purpose of this study was to evaluate prognostic factors, locoregional control, and survival in locally advanced bucco-alveolar complex cancers. METHODS: A retrospective review of 83 patients treated between January 2009 and December 2012 with bucco-alveolar complex cancers was conducted. All patients had surgery and adjuvant radiotherapy with intensity-modulated radiotherapy (IMRT) with/without concurrent chemotherapy. Survival analysis was performed using Kaplan-Meier and multivariable Cox regression model. RESULTS: On univariate and multivariate analysis, perineural invasion (PNI) was found to be an independent adverse risk factor. Patients with PNI-positive disease had significantly worse 2-year disease-free survival (DFS), locoregional failure free survival, and overall survival (OS) as compared to patients with PNI-negative disease (P < 0. 001, 0.001 and < 0. 001) respectively. CONCLUSION: Compared with patients with PNI-negative disease, patients with PNI-positive disease had much worse outcome despite aggressive adjuvant treatment. It warrants escalation of therapy and modification in radiation portals to cover neural pathways in patients with PNI-positive disease.

A comparison between four immobilization systems for pelvic radiation therapy using CBCT and paired kilovoltage portals based image-guided radiotherapy.

INTRODUCTION: We commonly use 6- and 4-clamped thermoplastic molds (TMs) for rigid immobilization during pelvic radiotherapy (RT), sometimes a vacuum cushion (VC) is also used as leg support with TM. Our objective was to report the setup margins (SMs) associated with the different systems, to analyze whether any of these systems is superior, and to analyze whether any of them showed better reproducibility in any particular direction. MATERIALS AND METHODS: Retrospective analysis was done by dividing the patients into four groups: 6-clamp with VC (6CVC), 6-clamp without VC (6CNC), 4-clamp with VC (4CVC), and 4-clamp without VC (4CNC). A repeat offline review was done for all patients and errors were tabulated. Statistical methods were then applied. RESULTS: Total 24 patients had 413 image-guided RT (IGRT) sessions, 312 were cone beam computed tomography scan (CBCT) scans and 101 were paired kilovoltage portals (kVp). There was no statistically significant difference between 6CVC and 6CNC. However, while comparing 4CVC and 4CNC, a statistically significant difference was seen in all directions. VC improved precision in vertical and lateral direction mainly, while the 6-clamped TM improved reproducibility in longitudinal direction. CONCLUSIONS: SM was low for all the four immobilization systems studied. There is no added benefit of using a VC with 6-clamped TM for pelvic RT. Use of a VC is recommended with 4-clamped TM to improve overall reproducibility. 6-clamped TM helps keep the errors low.

Prognostic factors and outcome analysis of submandibular gland cancer: a clinical audit.

PURPOSE: To retrospectively review a long-term, single-institution experience of subjects with submandibular gland malignancies treated with definitive locoregional therapy with an aim to identify clinicopathologic variables that correlate with outcomes. MATERIALS AND METHODS: A comprehensive chart review of 47 patients presenting to the institute from 1993 to 2005 with a histologic diagnosis of submandibular salivary gland cancer was performed to extract demographic data, clinicopathological characteristics, and treatment details. Clinical and pathologic factors were correlated with locoregional control, distant metastases free survival, and disease-free survival using log-rank test and Cox proportional hazards model for univariate and multivariate analysis, respectively. RESULTS: With a median follow-up of 29 months (interquartile range, 13 to 64 months), the actuarial 5-year locoregional control, distant metastasis-free survival, and disease-free survivals of the entire cohort were 80.5%, 86.1%, and 71.8%, respectively. Overall stage grouping (P = .008), perineural invasion (P = .04), and radiotherapy dose (P = .033) were significant predictors of locoregional control. Overall stage grouping (P = .014) and T stage (P = .05) also affected disease-free survival. Extraglandular involvement showed a trend toward poorer outcome. CONCLUSIONS: Submandibular gland cancer is a rare disease with histologic diversity and variable clinical behavior. Overall stage grouping and perineural invasion remain the most significant predictors of outcome. Adequate doses of adjuvant radiotherapy improve locoregional control in high-risk patients.

Treatment planning of epithelial ovarian cancers using helical tomotherapy.

Whole Abdomen Radiotherapy (WAR) for epithelial ovarian cancer though effective has been used sparingly due to inadequate target coverage and poor sparing of Organ At Risk (OAR) leading to significantly higher toxicities. Newer radiation techniques have shown potential for significant improvement in the therapeutic ratio. The purpose of this study was to evaluate Helical Tomotherapy(HT) for WAR. The objective parameters were to obtain uniform and adequate target coverage with maximum OAR sparing. HT plans were generated for five patients with field-width of 5.0/2.5 cm, modulation factor of 3.5/3.0, and a pitch of 0.3. A dose of 25 Gy in 25 fractions was prescribed to the abdomen with a simultaneous boost of 45 Gy in 25 fractions to the pelvis. Dose-volume parameters and various indices were analyzed and compared. Mean volume (standard-deviation) of abdominal and pelvic PTV (planning target volume) was 6630 +/-450 cm3 and 1235 +/-98 cm3 respectively. Mean length of PTV in cranio-caudal direction was 41+/-4 cm. Volume receiving 95% and 107% of the prescription dose, (V95% and V107%) was 95.6+/-2.7% and 2.6+/-0.5% for abdominal-PTV, and 95.7+/-2.4% and 0% for pelvic-PTV respectively. Homogeneity and Conformity indices were 17.5+/-1.7, 1.2+/-0.03 for abdominal PTV, and 5.2+/-0.7, 1.1+/-0.02 for pelvic-PTV respectively. Median dose received by the kidneys, liver and bone marrow were 9.6+/-1.2 Gy, 17+/-2.7 Gy and 22+/-1.4 Gy respectively. HT achieves an excellent coverage of WAR target with simultaneous pelvic boost and better organ (kidneys and liver) sparing. HT for WAR has the potential as consolidative therapy which is being evaluated further in a phase II cohort study in epithelial ovarian cancers.

Skin dose measurements using MOSFET and TLD for head and neck patients treated with tomotherapy.

The purpose of this work was to estimate skin dose for the patients treated with tomotherapy using metal oxide semiconductor field-effect transistors (MOSFETs) and thermoluminescent dosimeters (TLDs). In vivo measurements were performed for two head and neck patients treated with tomotherapy and compared to TLD measurements. The measurements were subsequently carried out for five days to estimate the inter-fraction deviations in MOSFET measurements. The variation between skin dose measured with MOSFET and TLD for first patient was 2.2%. Similarly, the variation of 2.3% was observed between skin dose measured with MOSFET and TLD for second patient. The tomotherapy treatment planning system overestimated the skin dose as much as by 10-12% when compared to both MOSFET and TLD. However, the MOSFET measured patient skin doses also had good reproducibility, with inter-fraction deviations ranging from 1% to 1.4%. MOSFETs may be used as a viable dosimeter for measuring skin dose in areas where the treatment planning system may not be accurate.

Flap reconstruction and interstitial brachytherapy in nonextremity soft tissue sarcoma.

Radiotherapy is an integral component of management of high-grade soft tissue sarcomas. Interstitial brachytherapy is used to deliver a boost or radical dose with several advantages over external beam radiotherapy. There has always been a concern to use brachytherapy with flap reconstruction of skin defects after wide excision. We preset our initial experience with interstitial brachytherapy in two patients of recurrent high-grade non-extremity sarcomas treated with surgical excision and soft tissue reconstruction of surgical defect.

Intraoperative high-dose-rate 192Ir radical implant in early breast cancer: a quality assurance and dosimetry study.

PURPOSE: To evaluate the variability in catheter length, geometry, and dosimetric parameters of radical intraoperative high-dose-rate breasts implant during 7-11 days. METHODS AND MATERIALS: Simulator X-rays, CT scans, and dosimetric studies were repeated on alternate days in 14 consecutive patients treated with radical intraoperative two- or three-plane nylon catheter high-dose-rate implant (34 Gy in 10 fractions within 5 days). RESULTS: Significant variation was found in catheter length, but no major change was noted in implant geometry, homogeneity, or inhomogeneity indexes. A variation in length of >5 mm in one or more catheters was seen in all patients and >10 mm in 11 patients at any time during the implant. Of the 171 catheters in 14 patients, 100 (58%) and 38 (22%) showed a variation of >5 mm or >10 mm, respectively. The variation of >10 mm was reduced from 32% of catheters in the first 5 patients to 17% in the subsequent 9 patients (p = 0.028). Rigid catheter fixation might reduce length variation but may cause skin necrosis if the expanding cavity indents the skin for a long period against the fixation device. A dose homogeneity index of 0.90 (range 0.85-0.92) and dose nonuniformity ratio of 0.20 (range 0.12-0.25) were satisfactory. CONCLUSION: The catheter fixation and exit catheter length should be measured daily and if the implant is in situ for more than a few days, orthogonal X-rays and, if indicated, dosimetry should be repeated at least once.