Cancer care continuum at a tertiary care centre in India during the Covid-19 pandemic and nationwide lockdown: Healthcare delivery through telemedicine.

Background The Covid-19 pandemic and subsequent lockdown in India caused disruptions in cancer treatment due to the restriction on movement of patients. We aimed to maintain continuity in cancer treatment during the lockdown through teleconsultations. We tried to reach out to our patients using telephonic consultations by establishing a Teleconsult Centre facility run by a team of doctors and patient navigators. Methods We telephonically contacted all patients who had outpatient appointments from 23 March to 30 April 2020 at our centre through the Teleconsult Centre to understand their current circumstances, feasibility of follow-up, local resources and offered best possible alternatives to continue cancer treatment, if required. Results Of the 2686 patients scheduled for follow-up during this period, we could contact 1783 patients in 9 working days. Through teleconsultations, we could defer follow-ups of 1034 patients (57.99%, 95% confidence interval [CI] 55.6%-60.3%), thus reducing the need for patients to travel to the hospital. Change in systemic therapy was made in 75 patients (4.2%, 95% CI 3.3%-5.2%) as per the requirements and available resources. Symptoms suggestive of disease progression were picked up in 12 patients (0.67%, 95% CI 0.35%-1.17%), who were advised to meet local physicians. Conclusion Our study suggests that the majority of patients on follow-up can be managed with teleconsultation in times of crisis. Teleconsultation has the potential of being one of the standard methods of patient follow-up even during periods of normalcy.

Salvage (Re)radiation in Oligometastatic and Oligorecurrent Cervical Cancer.

PURPOSE: In patients with recurrent or metastatic cervical cancer, the median survival time is 13 to 24 months based on the choice of palliative systemic chemotherapy. Evolving evidence suggests that the addition of radiation may lead to improved survival. METHODS AND MATERIALS: Consecutive patients treated with radiation with or without systemic chemotherapy for oligometastatic or oligorecurrent disease within the period from 2017 to 2020 were included. All patients received systemic chemotherapy consultation and radiation to relapsed or metastatic sites. Progression-free survival (PFS) was determined as the period between diagnosis of relapse or metastasis and the last progression of the disease. Overall survival (OS) was defined as the time between the date of diagnosis of relapse or metastasis and follow-up or death. The effect of various prognostic and predictive factors was estimated using the Kaplan-Meier method and log-rank test. RESULTS: Fifty-eight consecutive patients were included. The median time to relapse was 18 months (8-205 months). At the time of first relapse, 34.4% of patients (n = 20) had locoregional relapse, 32.8% (n = 19) had distant nodal metastases, and 32.8% (n = 19) had visceral metastases. The relapse was within previously irradiated portals in 34.5% (n = 20), out of field in 50% (n = 29), and both in 15.5% (n = 9) of patients. Overall, 56% of patients (n = 33) received systemic chemotherapy. The radiation therapy dose in equivalent doses of 2 Gy at the time of retreatment was 44 Gy (31-68 Gy). The median PFS and OS from the date of first relapse were 16 (12-19) and 28 months (2-108), respectively. Grade ≥3 toxicity was observed in 19% of patients. No patient- or treatment-related factor was identified as predictive of OS on univariate analysis. CONCLUSIONS: The use of potentially radical doses of radiation, including reirradiation at locoregional or distant oligorelapse or metastasis, is associated with encouraging PFS and OS in patients with cervical cancer.

Neurocognitive function and survival in children with average-risk medulloblastoma treated with hyperfractionated radiation therapy alone: Long-term mature outcomes of a prospective study.

Background: The purpose of this study was to report long-term neurocognitive and clinical outcomes in children treated for average-risk medulloblastoma with hyperfractionated radiation therapy (HFRT) alone. Methods: Between 2006 and 2010, 20 children with rigorously staged average-risk medulloblastoma were treated on a prospective study with HFRT without upfront adjuvant systemic chemotherapy after written informed consent. HFRT was delivered as twice-daily fractions (1 Gy/fraction, 6-8 hours apart, 5 days/week) to craniospinal axis (36 Gy/36 fractions) plus conformal tumor-bed boost (32 Gy/32 fractions). Neurocognitive function was assessed at baseline and periodically on follow-up using age-appropriate intelligence quotient (IQ) scales. Results: Median age was 8 years (range 5-14 years) with 70% being males. Mean and standard deviation (SD) scores at baseline were 90.5 (SD = 17.08), 88 (SD = 16.82) and 88 (SD = 17.24) for Verbal Quotient (VQ), Performance Quotient (PQ), and Full-Scale IQ (FSIQ) respectively. Mean scores remained stable in the short-to-medium term but declined gradually beyond 5 years with borderline statistical significance for VQ (P = .042), but nonsignificant decline in PQ (P = .259) and FSIQ (P = .108). Average rate of neurocognitive decline was <1 IQ point per year over a 10-year period. Regression analysis stratified by age, gender, and baseline FSIQ failed to demonstrate any significant impact of the tested covariates on longitudinal neurocognitive function. At a median follow-up of 145 months, 10-year Kaplan-Meier estimates of progression-free survival and overall survival were 63.2% and 74.1% respectively. Conclusion: HFRT alone without upfront adjuvant chemotherapy in children with average-risk medulloblastoma is associated with modest decline in neurocognitive functioning with acceptable long-term survival outcomes and may be most appropriate for resource-constrained settings.

Point-A vs. volume-based brachytherapy for the treatment of cervix cancer: A meta-analysis.

BACKGROUND & PURPOSE: To report disease-free survival (DFS) for volume-based and point-A based brachytherapy (BT) in locally advanced cervical cancer. MATERIALS & METHODS: We conducted a meta-analysis of studies assessing the effects of point-A and volume-based brachytherapy on 3-year DFS. Studies including stage I-IVA cervical cancer patients were included if standard treatment of concomitant chemo-radiotherapy and high-dose- or pulsed dose rate BT was delivered. The primary outcome was 3-year DFS, and secondary outcomes were 3-year local control (LC), 3-year overall survival (OS) and late toxicity. A random-effects subgroup meta-analysis was done. RESULTS: In total, 5499 studies were screened, of which 24 studies with 5488 patients were eligible. There was significant heterogeneity among point-A studies (1538 patients) (I2 = 82%, p < 0.05) relative to volume-based studies (3950 patients) (I2 = 58, p = 0.01). The 3-year DFS for point-A and volume-based studies were 67% (95% CI 60%-73%) and 79% (95% CI 76%-82%) respectively (p = 0.001). Three-year LC for point-A and volume-based studies were 86% (95% CI 81%-90%) and 92% (91%-94%) respectively (p = 0.01). The difference in 3-year OS (72% vs. 79%, p = 0.12) was not statistically significant. The proportion of prospectively enrolled patients was 23% for point-A studies and 33% for volume-based studies. There was no difference in late grade 3 or higher gastrointestinal (3% vs. 4%, p = 0.76) genitourinary toxicities (3% vs. 3% p = 0.45) between the two groups. CONCLUSION: Volume-based BT results in superior 3-year DFS and 3-year LC. In the absence of randomized trials, this meta-analysis provides the best evidence regarding transition to 3D planning.

Long-Term Clinical Outcomes and Sequelae of Therapy in Early-Stage Orbital Mucosa-Associated Lymphoid Tissue Lymphoma.

INTRODUCTION: Orbital mucosa-associated lymphoid tissue (MALT) lymphoma, which are rare and indolent, often present at an early stage. We report the efficacy and safety outcomes of treatment in these patients. METHODS: We analyzed adult patients with stage IE or IIE orbital MALT lymphoma between 1999 and 2017 treated at our institute. We assessed local control (LC) rates, overall survival (OS), relapse-free survival (RFS) using Kaplan Meier method and the incidence of late toxicities. RESULTS: Seventy patients were analyzed for clinical outcomes. The median age at diagnosis was 52 years (IQR-45-62 years). Radiotherapy was offered to 97% of patients and the dose ranged from 36 to 45 Gy. Chemotherapy was administered in 5(7.1%) patients. Relapse occurred in 8 patients (local: 2, distant: 6). At a median follow-up of 101 months (IQR-47-146 months), the median OS and RFS was not reached. 8-year OS, RFS and LC rates were 96.5%, 88.5%, 96.7% respectively. Univariate analysis showed age ≤60 years and lacrimal involvement significantly correlated with better OS (P = .01 and .04, respectively). Cataract was the most common sequelae observed in 31 patients (44.3%). CONCLUSION: Moderate doses of radiotherapy are curative in early-stage orbital MALT lymphoma with favorable clinical outcomes. Lower doses of radiation can reduce the toxicity further, without compromising efficacy.

Prognostic impact of semantic MRI features on survival outcomes in molecularly subtyped medulloblastoma.

PURPOSE: Imaging features are known to reflect inherent disease biology in various cancers including brain tumors. We report on the prognostic impact of magnetic resonance imaging (MRI) features on survival in patients with medulloblastoma treated between 2007 and 2018 at our institute. METHODS: Sixteen semantic imaging features (with predefined categories) were extracted from pre- and postcontrast T1-weighted and T2-weighted MRI by consensus. Univariate analysis and multivariate Cox regression analysis were performed to assess the correlation of semantic features with relapse-free survival (RFS) and overall survival (OS). RESULTS: The study cohort comprised 171 medulloblastoma patients (median age 9 years) treated with maximal safe resection followed by risk-stratified adjuvant radio(chemo)therapy. A total of 55 patients experienced recurrent/progressive disease (commonly neuraxial metastases) resulting in 44 deaths, including one treatment-related death. At a median follow-up of 45 months (interquartile range 19-65 months), 5­year Kaplan-Meier estimates of RFS and OS were 64% and 71%, respectively. Semantic MRI features such as non-central tumor location on vertical axis, absence of brainstem involvement, ≤ 80% solid tumor area with contrast uptake, heterogenous pattern of contrast enhancement, necrosis, calcification, and T2-weighted heterogeneity were associated with significantly worse RFS and/or OS in univariate analysis. Cox regression analysis identified tumor location on the vertical axis, brainstem involvement, and calcification as independent prognostic factors impacting outcomes. Distinctive MRI features correlated with survival even within individual molecular subgroups of medulloblastoma. CONCLUSION: Distinctive semantic MRI features correlate significantly with survival outcomes in medulloblastoma, also within individual molecular subgroups, reflecting their prognostic impact.

Hydroxychloroquine in the treatment of coronavirus disease 2019: Rapid updated systematic review and meta-analysis.

Coronavirus disease 2019 (COVID-19) caused by the novel severe acute respiratory syndrome coronavirus 2 continues to grow and spread throughout the world since being declared a pandemic. Despite extensive scientific research globally including repurposing of several existing drugs, there is no effective or proven therapy for this enigmatic disease which is still largely managed empirically This systematic review evaluated the role of hydroxychloroquine (HCQ) in the treatment of COVID-19 infection and was conducted using Cochrane methodology for systematic reviews of interventional studies including risk of bias assessment and grading of the quality of evidence. Only prospective clinical trials randomly assigning COVID-19 patients to HCQ plus standard of care therapy (test arm) versus placebo/standard of care (control arm) were included. Data were pooled using the random-effects model and expressed as risk ratio (RR) with 95% confidence interval (CI). A total of 10,492 patients from 19 randomised controlled trials were included. The use of HCQ was not associated with higher rates of clinical improvement (RR = 1.00, 95% CI: 0.96-1.03, p = 0.79) or reduction in all-cause mortality by Day14 (RR = 1.07, 95% CI: 0.97-1.19, p = 0.19) or Day28 (RR = 1.08, 95% CI: 0.99-1.19, p = 0.09) compared to placebo/standard of care. There was no significant difference in serious adverse events between the two arms (RR = 1.01, 95% CI: 0.85-1.19, p = 0.95). There is low-to-moderate certainty evidence that HCQ therapy is generally safe but does not reduce mortality or enhance recovery in patients with COVID-19 infection.

Systematic review and meta-analysis of randomised controlled trials testing the safety and efficacy of convalescent plasma in the treatment of coronavirus disease 2019 (COVID-19): Evidence-base for practise and implications for research.

BACKGROUND: Despite scientific advances, there is no effective medical therapy for coronavirus disease 2019 (COVID-19). This systematic review and meta-analysis aimed to evaluate the safety and efficacy of convalescent plasma therapy in COVID-19. METHODS: This review was carried out in accordance with Cochrane methodology including risk of bias assessment and grading of the quality of evidence. Only prospective clinical trials randomly assigning COVID-19 patients to convalescent plasma plus standard of care therapy (test arm) versus placebo/standard of care (control arm) were included. Two reviewers independently read each preprint/publication and extracted relevant data from individual studies. Data were pooled using the random-effects model and expressed as risk ratio (RR) with 95% confidence interval (CI). RESULTS: A total of 13 206 patients from 12 randomised controlled trials were included. There was no significant difference in clinical improvement rate (RR = 1.00, 95% CI: 0.98-1.02, p = 0.96) or time to clinical improvement (median difference of 1.08 days with 95% CI ranging from -0.15 to +2.30 days) between convalescent plasma versus placebo/standard of care therapy. The use of convalescent plasma was not associated with significantly reduced risk of death (RR = 0.81, 95% CI: 0.65-1.02, p = 0.08). Reassuringly, overall incidence of infusion-related serious adverse events was low (3.25%) and not significantly different (RR = 1.14, 95% CI: 0.93-1.40, p = 0.22) for convalescent plasma transfusion compared to placebo/standard of care therapy. CONCLUSIONS: There is low to moderate certainty evidence that the addition of convalescent plasma to current standard of care therapy is generally safe but, does not result in any significant clinical benefit or reduction of mortality in COVID-19.

Meeting the Global Need for Radiation Therapy in Cervical Cancer-An Overview.

Cervical cancer is the fourth most frequently diagnosed cancer and the fourth leading cause of cancer death in women. The discrepancy in cervical cancer incidence and mortality between developed and developing nations has become increasingly apparent with 84% of the incidence and 88% of the mortality of cervical cancer occurring in low income countries. Access to comprehensive cancer care is a challenge and in particular the radiotherapy facilities. The radiotherapy infrastructure requirement is grossly inadequate with only 30% of the needs available and is even worst in LIC's with only 3% facilities. Additionally, lack of brachytherapy facilities and expertise in LIC's and LMIC's compounds the issue further. Even with continued HPV vaccination programs, there will still be a substantial burden of cervical cancer patients for treatment. Introspection and review in international and national policies, augmentation of (i) infrastructure - affordable & sustainable, (ii) manpower and rigorous training in accessible regions would be vital. International and National collaborative efforts among global organizations and societies, periodic peer reviews, resource stratified treatment guidelines and research, and health education would contribute further to women health. The amalgamation of palliative and hospice care services and radiotherapy facilities seamlessly would be a major step for comprehensive management of cervical cancer patients.

Optimal adjuvant therapy in elderly glioblastoma: results from a systematic review and network meta-analysis.

BACKGROUND: There exists lack of consensus worldwide regarding the most optimal adjuvant therapy regimen in elderly patients with newly-diagnosed glioblastoma (GBM). PURPOSE: To identify the most optimal adjuvant therapy regimen in elderly GBM patients through systematic review and network meta-analysis. METHODS: Prospective trials randomly assigning elderly GBM patients post-operatively to any adjuvant therapy regimen were included. The primary outcome measure was overall survival. Numbers of events, patients at-risk, and censored patients for survival were estimated from Kaplan-Meier survival curves in the interval of 0-12 months. The total person-time at risk and the mortality × 100 person-months was also estimated. The relative ranking probability of each treatment and rankograms were used to estimate the hierarchy of each intervention in terms of overall survival. The mean rank values and the surface under the cumulative ranking (SUCRA) curves were also calculated. RESULTS: A systematic literature search identified 1278 abstracts, that were screened to retrieve full-text manuscripts of potentially eligible articles. After detailed assessment, data from 1569 patients in 7 randomized controlled trials (RCTs) treated with one of following regimens was extracted and analyzed: normofractionated radiotherapy (RT) delivered over 5.5-6 weeks; moderately hypofractionated RT (2-3 weeks) either alone or in combination with temozolomide or bevacizumab; extremely hypofractionated RT (1-week); temozolomide monotherapy; and best supportive care alone. In terms of overall survival, moderately hypofractionated RT (3-weeks) with concurrent and adjuvant temozolomide emerged as the best and second-best adjuvant therapy option with 81% probability and 99.1% probability respectively. Using SUCRA, the surface area for moderately hypofractionated RT (3-weeks) with concurrent and adjuvant temozolomide reached almost 100%, confirming it as the best intervention. As expected, best supportive care alone was ranked as the worst treatment strategy. CONCLUSION: Moderately hypofractionated RT (3-weeks) with concurrent and adjuvant temozolomide is the most optimal and preferred adjuvant therapeutic regimen in elderly GBM.

Pattern of Gustatory Impairment and its Recovery after Head and Neck Irradiation.

INTRODUCTION: The majority of patients receiving concurrent chemoradiotherapy frequently complain of changes in their taste perception, and other distressing symptoms affecting their quality of life. This study was undertaken to determine the pattern of gustatory impairment and its recovery in irradiated head and neck cancer patients in India. MATERIALS AND METHODS: Thirty patients undergoing radical head and neck irradiation were enrolled and assessed for the four basic taste quality (sweet, salt, sour and bitter) by a forced three-choice stimulus drop technique measuring their taste recognition thresholds at baseline, weekly during radiation therapy (RT) and every month for 6 months following completion of RT. RESULTS: The maximum taste loss for any taste quality developed after the third week of RT. Irrespective of the taste quality, the majority of patients developed their maximum taste loss in the fourth to sixth week. The maximum taste loss was highest (100%) for the bitter taste and least (40.7%) for the sweet taste. Taste recovery for sweet, salt and sour taste qualities started from the first month onwards, but not for bitter taste. All taste qualities were severely affected in patients with primary involvement of the oral cavity and oropharynx as compared with nasopharynx, hypopharynx and laryngeal tumors. CONCLUSIONS: Taste dysfunction is a frequently ignored adverse effect of head and neck cancer treatment, seriously affecting the patient's quality of life. Clinicians must make patients aware of this specific gustatory dysfunction and its pattern of recovery. Future efforts should be directed towards minimizing this dysfunction, specifically in tumors arising from the oral cavity and oropharynx.

Malignant peripheral nerve sheath tumor of the anterior mediastinum: a rare presentation.

Malignant peripheral nerve sheath tumor (MPNST) is a rare tumor that accounts for 5% of all thoracic neoplasm usually located in the posterior mediastinum and is generally associated with a poor outcome. We present a case of MPNST of the anterior mediastinum presenting in a rare location leading to diagnostic dilemmas and treated primarily by surgical resection.