The Growing Burden of Cancer in Adolescent and Young Adults in Asia: A Call to Action.

Recent estimates suggest that the lower middle income countries in Asia carry the heaviest burden of cancer among adolescents and young adults (AYAs) (defined as age 15-39 years). A larger proportion of the population in Asia is aged 15-39 compared with the developed countries. This age group is different from the pediatric or the adult group in terms of physical, social, psychological, and financial needs. Cancer incidence, disability, survivorship needs, financial toxicity, psychosocial issues, and so on are underestimated in this group, and available literature is scarce. Global data show an increasing trend of adult-onset cancers such as colorectal, breast, pancreas, and lung in the AYA population. Data suggest that the disease biology and prognosis are different in this group; however, further research is needed. An ESMO/SIOPE/SIOP Asia survey on the care of AYA cancer patients in Asia found a suboptimal availability of AYA specialized centers in the region and identified several unmet needs including lack of training, clinical trials, and high rates of treatment abandonment. There is an urgent need for cancer care systems in Asia to develop specialized services to be able to cater to this growing burden. Training and research in this area also need to be upscaled with the goal of establishing a sustainable infrastructure and quality services to ensure that this vulnerable group receives appropriate care. Management guidelines and national health policies should consider giving special attention to this group as the World Health Assembly reinforces the inclusion of children and adolescents in cancer control programs.

Cardiotoxicity in breast cancer treatment: Causes and mitigation.

Survivorship issues and treatment related toxicities have considerably increased in breast cancer patients following improved therapeutic options. Cardiotoxicity has been a major treatment related side effects in these patients. Despite this being a well-known entity, the real magnitude of the problem remains an enigma. The amount of research in mitigation of cardiotoxicity or its management in breast cancer survivors is limited and there is an urgent need for finding solutions for the problem. In this article, we are reviewing the agents that cause cardiotoxicity and suggesting a proposal for follow up of breast cancer survivors in an attempt to reduce the magnitude of impact on their quality of life.

Assessment of late treatment-related symptoms using patient-reported outcomes and various factors affecting return to work in survivors of breast cancer.

Introduction: Breast cancer is the most common cancer in women worldwide. Survival in these patients has increased because of early diagnosis and multimodality treatment methods. Return to premorbid functional status after treatment is essential for rehabilitation and good quality of life. Many patients suffer from late treatment-related symptoms which affect their return to premorbid status. Various health-related and work-related variables also affect the return to premorbid status. Materials and methods: This is a cross-sectional study in which 98 patients with breast carcinoma who received curative treatment were included 6-12 months post-radiotherapy completion. Patients were interviewed to assess their type of work and hours of work prior to diagnosis and at the time of the study. The extent to which they are able to return to their pre-diagnosis level of work was noted and various factors that were hindering them were documented. Treatment-related symptoms were assessed using selected questions from NCI PRO-CTCAE (version 1.0) questionnaire. Results: The median age of diagnosis of patients included in the study was 49-50 years. The most common symptoms experienced by patients were fatigue (55%), pain (34%) and oedema (27%). 57% of patients were employed before diagnosis, of which only 20% were able to return to their employment post-treatment. All patients were involved in household work prior to diagnosis and 93% were able to get back to their routine household work, with 20% of patients requiring frequent work breaks. About 40% of patients reported social stigma as a factor that hindered them from returning to work. Conclusion: Most patients return to household work post-treatment. Fatigue, pain and social stigma were the most common barriers to return to employment. Patient-reported outcomes and functional assessments can enable better survivorship care.

Impact of various prognostic factors on survival in glioblastoma: tertiary care institutional experience.

Introduction: Glioblastoma is the most common malignant brain tumour in adults. Among all gliomas, it is the most aggressive type, with a high fatality rate, and according to the WHO classification, it is a grade IV tumour. As this tumour is well-known for its poor survival, an understanding of clinical and treatment-related prognostic factors can help in tailored treatment. The aim of this study was to know the impact of prognostic factors on survival in these cases. Materials and methods: All glioblastoma patients treated in our hospital during 2010-2015 were included in the analysis. Cases were divided into different groups based on prognostic factors. Overall survival (OS) and disease-free survival (DFS) were calculated and compared among the different groups. Statistical analysis was carried out using SPSS software v20. Results: One-year OS was 36.9% and 2-year OS was 10.8%. One-year DFS was 13.04%. On univariate analysis, age at presentation ≤45 years and adjuvant chemotherapy with six cycles or more temozolomide improved OS and DFS. Multivariate analysis retained the statistically significant positive impact of usage of adjuvant temozolomide chemotherapy of ≥six cycles on OS and DFS. The use of the anti-epileptic drug Levetiracetam had a statistically significant improvement of DFS. Conclusion: Among various clinical and treatment-related prognostic factors evaluated in our study, younger age at presentation and addition of temozolomide chemotherapy to radiation showed improvement in OS and DFS. The use of the anti-epileptic drug Levetiracetam had an impact on DFS in glioblastoma patients.

Correlation of Target Volumes on Magnetic Resonance Imaging and Prostate-Specific Membrane Antigen Brain Scans in the Treatment Planning of Glioblastomas.

Background: Imaging of gliomas/glioblastomas has always been challenging. Many magnetic resonance imaging (MRI) techniques are available for imaging glioblastomas. MRI cannot always differentiate tumor from nonspecific changes and postoperative changes in brain tissue. Among the new positron emission tomography-computed tomography (PET-CT) tracers, gallium-68 prostate-specific membrane antigen (Ga-68 PSMA-11 PET-CT) appears to be the most promising one. The absence of uptake by normal brain parenchyma leads to high tumor-to-background ratio leading to better visualization of the tumor. Objective: The aim of this study was to assess the correlation of target volumes on MRI and PSMA brain scans in the treatment planning of glioblastomas. Materials and Methods: Twenty-four patients in the age group of 5-75 years with histologically proven glioblastoma were included in the study following maximum safe resection. Simulation for treatment planning was done with Ga-68 PSMA PET-CT brain with IV iodine-based contrast. The pre- and postoperative MRI images were fused with PSMA simulation images. Gross tumor volumes (GTVs) contoured on T1-contrast MRI and on PSMA scans were compared. Results: GTV contoured on MRI and PSMA brain scans showed complete overlap in 17 patients. In seven patients, the target volumes drawn on Ga-68 PSMA brain scans were slightly smaller than the target volumes drawn on MRI brain scans. This difference in volumes could be due to postoperative changes which showed enhancement on the MRI scan. Conclusion: Ga-68 PSMA PET-CT shows good correlation with MRI brain in the evaluation and RT planning in glioblastomas. Tumor necrosis and postoperative changes did not show PSMA uptake. Precise target delineation on PSMA PET-CT can potentially result in smaller and more accurate GTVs, which in turn would result in less RT-induced side effects.

Chemoradiation with Weekly Paclitaxel and Carboplatin in Esophageal Squamous Cell Carcinoma: A Prospective Study.

Objective Neoadjuvant chemoradiation (CRT) using paclitaxel and carboplatin has significantly improved the survival rates in carcinoma esophagus, especially in squamous cell carcinoma (SCC). This regimen has not been adequately explored prospectively as a definitive CRT strategy. Our aim was to evaluate the efficacy, toxicity, and compliance to this regimen in a prospective setting in locally advanced esophageal SCC. Materials and Methods Patients with locally advanced esophageal SCC were planned for definitive CRT by using weekly paclitaxel 50 mg/m 2 and carboplatin area under curve 2 along with radical radiotherapy to a dose of 50.4 to 54 Gy. Treatment-related toxicity was assessed by using the common terminology criteria for Adverse Events Version 4.0, and the response was assessed by using endoscopy and computed tomography (CT) 4 to 6 weeks following CRT. The pathological response was documented for those who underwent surgery. Results Fifteen patients were included in the study, and all patients completed the planned course of radiation. The median number of chemotherapy cycles received was four. In total, 66% of the patients had delay or interruptions in chemotherapy, mostly due to neutropenia, and 66% of the patients had a clinical complete response (CR). Four patients underwent definitive esophagectomy, and the histopathology revealed pathologic CR. Overall CR rate was 80%. The median overall survival was 14 months, and 1-year survival was 57%. Conclusion Definitive CRT in esophageal SCC using weekly paclitaxel and carboplatin was relatively well tolerated with manageable toxicities and good clinical response rates. It may potentially represent a new standard of care as definitive therapy in the management of these tumors.

Outcomes in patients of carcinoma cervix Stage IIIB treated with definitive radiotherapy.

BACKGROUND: Cervical cancer is the fourth most common cancer in women. Although cervical cancer screening is available in India, there is lack of awareness and access to screening services. Consequently, most cancers are diagnosed in advanced stagesoften with obstructive uropathy. PATIENTS AND METHODS: This was a retrospective study of stage III B (as per pre-2018 FIGO staging) cervical cancer patients who received radiotherapy at our center between 2012 and 2019. Patients with or without obstructive uropathy, age group between 18 and 85 years, were included. Definitiveradiotherapy (RT) was delivered with 3D CRT to a dose of 50 Gy in 25 fractions over 5weeks given to whole pelvis and boost of 54 Gy was given to para-aortic or retroperitoneal lymph nodes when enlarged. All patients received intracavitary brachytherapy. RESULTS: 3-year overall survival rates for patients who received only RT was 24% versus 71% for those who received chemoradiotherapy (p = 0.0001). 5-year survival for patients who received RT alone was 12% versus 63% for those who received chemoradiotherapy (p = 0.0001). 3-year PFS was 77% versus 83% and those with and without obstructive uropathy respectively. (p = 0.0001). Overall, 37(56%) patients were alive without any evidence of recurrence. CONCLUSION: Early recognition and appropriate intervention for obstructive uropathy can potentially limit the detriment to outcomes in these patients and result is good long-term cure rates in these patients.

Optimizing e-learning in oncology during the COVID-19 pandemic and beyond.

The coronavirus disease 2019 (COVID-19) pandemic has profoundly impacted cancer care, research and residency training in oncology worldwide. Many countries canceled exams, shortened their residency program and medical school tenure. Traditional teaching and learning method has faced significant disruption during this time and the situation has pushed us to adapt to e-learning. Most national and international cancer meetings were converted into a virtual platform during this time. E-learning ensures a safe environment to maintain education during a pandemic. Digital technology-based learning is likely to be used effectively in oncology training even after the pandemic ends. Stakeholders should work towards standardizing e-learning into routine educational modules and create a system of credibility and accountability.

Return to work in survivors of Primary Brain Tumours treated with Intensity Modulated Radiotherapy.

MINI: Primary Brain Tumour survivors usually have significant morbidity, especially cognitive and neurological dysfunction. Return to pre-diagnosis work can be an important QoL indicator and outcomes measure in these patients. We did a retrospective study to assess return to work amongst the patients who underwent radiotherapy at our centre. BACKGROUND: Primary brain tumour (PBT) survivors have a high burden of morbidity. Return to work (RTW) is an important survivorship parameter and outcomes measure in these patients, especially in developing countries. This study was done to assess RTW after radiotherapy, reasons for no RTW, and relationship of RTW with treatment and patient factors. PATIENTS AND METHODS: A single centre study was done amongst PBT patients. Baseline and treatment details, education, employment was assessed. RTW assessed as: time to RTW, full/ part-time, reasons for no RTW and RTW at 6 months post-therapy, and last follow up. RESULTS: 67 PBT patients with a median age of 42 years were assessed. Most common diagnosis was low grade glioma. Over 66% patients were illiterate, and 62% had semi-skilled and unskilled jobs, mostly agriculture. About 64.4% patients returned to employment in a median time of 3 months. At 6 months post-treatment 58.2% had a job, with only 42% working full-time. 'Limb weakness' (21.4%), followed by 'loss of job/ no job' (16.7%), 'fatigue'/ 'tiredness' (14.3%), 'poor vision/ diminished vision' (11.9%) were the common reasons for no RTW. The factors found to be significantly associated with return to work were younger age (p = 0.042), male sex (0.013), the absence of complications during radiotherapy (p = 0.049), part time job prior to diagnosis (p = 0.047), and early return to work after RT (p < 0.001). CONCLUSION: Studies are needed to identify the barriers in re- employment and steps to overcome them in cancer patients.

"A prospective study of assessment of neurocognitive function in illiterate patients with gliomas treated with chemoradiation": Assessment of neurocognitive function in gliomas.

OBJECTIVE: Neurocognitive functioning (NCF) is an important component of quality of life (QoL) in glioma patients. The neurocognitive toxicity from irradiation of brain tumours may be related to damage to neural progenitor cells (NPC). The aim of our study was to assess the NCF in illiterate glioma patients. METHODS: This was a prospective study done in glioma patients admitted for adjuvant treatment. Illiterate and semiliterate post op glioma patients with ECOG PS ≤ 3 were included. Neurocognitive assessment was done using Addenbrooke's Cognitive Examination (ACE-III) questionnaire prior to the start of RT and at 6month and 12 month follow up. The scores were correlated to the doses to sub ventricular zone (SVZ) and sub granular zone (SGZ) regions. RESULTS: 20 patients were recruited.16 patients were illiterate and four patients were semiliterate. Median of the mean dose to the SVZ I/L (ipsilateral) was 48.5 Gy and SGZ I/L was 39.5 Gy. In patients who received ≤49 Gy mean dose to SVZ I/L, there was statistically significant improvement in memory, fluency, language and total ACE scores at six months. In patients with SGZ I/L mean dose ≤40 Gy, there was improvement in memory, language, and total ACE score at six months. Similar trend continued at 12 months follow up. CONCLUSIONS: NCF assessment by ACE III questionnaire is a useful tool even in illiterate patients. Lower RT doses to the ipsilateral SVZ and SGZ showed significant improvement in total ACE scores at 6 months and improvement in specific domains at 6 and 12 months.

Cisplatin induced cerebral sinus venous thrombosis in cervical cancer patients treated with concurrent chemoradiation: a case series.

Cisplatin is a widely used chemotherapeutic agent. Concurrent chemotherapy with cisplatin is an important component in the management of carcinoma cervix. The common side effects of cisplatin chemotherapy include nausea, vomiting, dyselectrolytemia, nephrotoxicity, etc. These side effects are anticipated and managed during chemotherapy. Thromboembolic events are rare complications with cisplatin. We present three cases of cisplatin related cerebral sinus venous thrombosis (CSVT). These patients were receiving concurrent chemoradiation for carcinoma cervix. These patients presented with neurological symptoms and were evaluated and diagnosed with CSVT. They recovered after appropriate management. Clinicians should be aware that CSVT, though uncommon, is a life threatening complication during cisplatin chemotherapy which should be appropriately evaluated and effectively managed.

Synchronous bilateral breast cancer patients treated with hypofractionated bilateral breast irradiation: A dosimetric and clinical study.

BACKGROUND: Bilateral breast irradiation is technically challenging and there is limited information regarding optimal technique and outcomes. Hypofractionated Radiotherapy (HFRT) has emerged as the new standard of care in early breast cancer. However, there are concerns in using hypofractionation for bilateral breast irradiation due to larger volumes and potential toxicity. Our aim was to analyze the dosimetric data and clinical outcomes in these patients. MATERIALS AND METHODS: Patients with synchronous bilateral breast cancer (SBBC) treated with bilateral breast irradiation were analyzed. All patients received simultaneous bilateral breast with or without regional nodal irradiation using a hypofractionated schedule of 40 Gy in 15 fractions over 3 weeks with single isocenter bi-tangential field-in-field intensity-modulated radiation therapy (FIF-IMRT) technique. RESULTS: Seven patients of SBBC were treated at our institute from 2015 to 2017. All patients were postmenopausal females. Five patients underwent bilateral modified radical mastectomy; two patients underwent bilateral breast conservative surgery. All patients received systemic anthracycline-based chemotherapy. The mean cardiac dose was 3.73 ± Gy and V 25 was 3.26% ± 1.96%. V 20 of lung ranged from 23.48% ± 4.47% and the mean esophageal dose was 3.6 ± 2.00 Gy. No patient had acute toxicity higher than Grade 2. At a median follow-up of 48 months, one patient died due to systemic progression. No patient reported any late toxicity. CONCLUSION: Bilateral breast irradiation using a hypofractionated schedule with single isocenter FIF-IMRT technique is technically feasible with minimal acute toxicity and no significant late effects on early follow-up.

Assessment of toxicities and outcomes in patients with breast cancer treated with hypofractionated radiotherapy.

BACKGROUND: Hypofractionation is now becoming the standard of care in breast irradiation. The aim of this study was to assess the toxicities and outcomes in patients with breast cancer treated with hypofractionated radiotherapy (HFRT). METHODS: Patients with localized breast cancer who received adjuvant HFRT between 2013 and 2015 with a minimum follow-up of 6 months following radiation were included in this prospective study. Late toxicities were assessed using CTCAE v 4 and included chest/breast pain, limb pain, limb edema, skin pigmentation, skin fibrosis, and shoulder movement restriction. Outcomes assessed included locoregional control, disease-free survival, and overall survival. Statistical analysis was done using Microsoft Excel and SPSS v22. RESULTS: A total of 81 patients fulfilled the inclusion criteria, of which 19 patients had died during follow-up. Regional nodal irradiation was done in 63 (77.8%) patients using the same hypofractionated schedule of 40 Gy in 15 fractions. Late toxicities were assessed for 62 patients. The median follow-up following the course of hypofractionated radiation was 45 months (range 14 - 65 months). Late toxicities were assessed for 62 patients. Grade 1/2 chest/breast pain, limb pain, limb edema, skin pigmentation, skin fibrosis, and shoulder movement restriction were seen in 11%, 12%, 7%, 6%, 8%, and 11% of cases, respectively. Distant recurrences were seen in 8% of cases, and there were no locoregional recurrences. Five-year overall survival was 76.5%. CONCLUSION: HFRT to whole breast or chest wall and the regional nodal areas was well-tolerated with acceptable rates of late toxicities on follow-up.

Prospective study to assess the survival outcomes of planned irradiation of ipsilateral subventricular and periventricular zones in glioblastoma.

PURPOSE/OBJECTIVES: Retrospective evidence suggests that the irradiation of stem cells in the periventricular zone (PVZ), specifically the subventricular zone (SVZ), to higher doses may be associated with improved outcomes. MATERIALS/METHODS: This was a prospective study, done from 2012 to 2017 in glioblastoma patients to assess the efficacy of planned irradiation of ipsilateral PVZ and SVZ on survival outcomes. The clinical target volume included the tumour bed with a 1.5-2 cm margin, perilesional oedema and was expanded to encompass the ipsilateral PVZ (5 mm lateral expansion adjacent to the ventricles, including the SVZ, which was a 5 mm expansion lateral to lateral ventricle). The ipsilateral PVZ was planned to receive a dose of ≥50 Gy. RESULTS: 89 patients were recruited of which 74 patients were available for the analysis. Median age was 48 years. Mean doses to ipsilateral PVZ and SVZ were 56.2 and 55.1Gy, respectively. Median overall survival in the entire group was 13 months. There was no significant correlation between survival and doses to ipsilateral, contralateral, or bilateral PVZ and SVZ. Median survival was 16, 12 and 6 months for Eastern Cooperative -Oncology Group (ECOG) PS 1, 2 and 3, respectively (p = 0.05). CONCLUSION: Planned irradiation of potential stem cell niches in the ipsilateral cerebral hemisphere did not result in improved survival as suggested by retrospective studies. Doses to contralateral or bilateral PVZ or SVZ also did not influence survival.

Effect of radiation dose to the periventricular zone and subventricular zone on survival in anaplastic gliomas.

PURPOSE: Evidence suggests a correlation of subventricular zone (SVZ) irradiation on survival. Most of the data have been analysed in glioblastoma patients. The aim of this study is to analyse the dose to the subventricular and periventricular zone and its outcomes in anaplastic gliomas. MATERIALS AND METHODS: A retrospective analysis of patients with anaplastic gliomas were admitted for post-chemoradiation from January 2010 to June 2016 was done from treatment records. SVZ was contoured as 5 mm expansion along the lateral margin of the lateral ventricles, and PVZ was contoured as 5 mm lateral expansion adjacent to ventricles. Dosimetric data were collected from the treatment planning system. RESULTS: Ninety-five patients were included in the analysis. The median age was 35 years. Two- and five-year overall survival (OS) for the entire group was 84% and 54.2%, respectively. Two- and five-year progression-free survival (PFS) was 79.8% and 50.6%, respectively. Patients receiving <54 Gy to the i/l SVZ showed a significantly better PFS and OS. 5-Year OS was 72.6% in this group compared to 37% for the group receiving ≥54 Gy (p = 0.01). Five-year PFS was 69.9% in this group compared to 31.9% for the group receiving ≥54 Gy (p = 0.02). However, this was not significant in multivariate analysis. CONCLUSION: Increased dose to the ipsilateral SVZ does not correlate with improved survival in anaplastic gliomas. There is conflicting evidence regarding the benefit of irradiating the stem cell zones. Future studies should focus on optimizing doses to these areas to reduce detriment in neurocognition.

Effect of valproic acid on survival in glioblastoma: A prospective single-arm study.

BACKGROUND: Retrospective evidence suggests that valproic acid (VPA), an antiepileptic drug, is associated with improved outcomes in glioblastoma. The exact mechanism of interaction of VPA with radiation and temozolomide (TMZ) is still unclear. Laboratory studies show that VPA can enhance tumor cell kill while at the same time protect the normal neural tissue. The aim of this study was to prospectively evaluate the benefit of VPA on outcomes in glioblastoma. MATERIALS AND METHODS: In this single-arm prospective study, patients of glioblastoma were started on seizure prophylaxis with VPA (15-20 mg/kg/day) following maximal safe resection. All patients were treated with chemoradiation to a dose of 60 Gy in 30 fractions with concurrent TMZ followed by adjuvant TMZ for 6 cycles. VPA was continued during adjuvant treatment and follow-up. Survival analysis was done using Kaplan-Meier analysis. RESULTS: Twenty patients were enrolled in the study. Median age was 47 years. M:F ratio was 3:1. Treatment was well tolerated with no grade 3/4 adverse events. 8/20 patients experience seizure episodes during treatment and/or follow-up which needed additional antiepileptic drugs for control. Median progression-free survival (PFS) and overall survival (OS) were 10 months and 16 months, respectively. Younger patients (age ≤45 years) showed a significantly better OS (25 months) versus older patients (8 months) (P = 0.002). CONCLUSIONS: Incidence of seizures on VPA prophylaxis was 40%. Median PFS and OS were comparable to historical controls. There was no significant treatment-related toxicity. The results need validation in larger prospective randomized studies.

Prognostic factors and outcomes in anaplastic gliomas: An institutional experience.

BACKGROUND: There is lack of clear evidence and treatment guidelines for anaplastic gliomas (AGs) with very few studies focusing exclusively on these patients. The aim of the study was to analyze the clinical profile and survival in these patients. MATERIALS AND METHODS: Patients of AGs treated with radiation and concurrent ± adjuvant chemotherapy from January 2010 to December 2015 were analyzed. Statistical analysis was done using SPSS version 20 software. RESULTS: A total of 100 patients were included in the study. The median age was 35 years (range 6-68 years). Eighty-four patients had follow-up details and were included for survival analysis. The 5-year overall survival (OS) was 58%. Age, presentation with seizures, and focal neurological deficit were not found to significantly influence survival. The 5-year survival for oligodendroglioma and astrocytoma was 69% and 52%, respectively. Patients with Karnofsky Performance Score (KPS) of ≥70 had a significantly better 5-year OS (65%) as compared to those with KPS <70 (33%) (P = 0.000). The use of adjuvant temozolomide (TMZ) showed longer 5-year OS of 67.7% compared to 36% in patients who did not receive adjuvant chemotherapy (P = 0.018). Patients receiving both concurrent and adjuvant TMZ showed longer 5-year OS (68.5% vs. 40%, P = 0.010). Twenty-two patients had recurrence with average time to recurrence being 37 months. Fourteen patients underwent salvage surgery and two patients received reirradiation. CONCLUSIONS: OS significantly correlated with KPS and receipt of concurrent and adjuvant chemotherapy with TMZ. Therefore, adjuvant radiation with concurrent and adjuvant TMZ should be the standard of care for AGs.

Radiotherapy in aggressive cutaneous pseudolymphoma: a case report and review of literature.

Pseudolymphoma is a nonspecific disease characterized by lesions with lymphomatous-appearing but benign accumulation of inflammatory cells. They generally present as small ulcero-nodular lesions confined to skin which often respond to local therapies. We describe an unusual presentation of an extensive and locally aggressive cutaneous pseudolymphoma in a 21-year-old male patient who presented with extensive cutaneous eruptions gradually progressing over 6 years to involve the entire circumference of his left arm. Magnetic resonance imaging scans of his left arm showed a lesion deeply infiltrating into the soft tissue reaching up to the humerus with intense periosteal reaction. He was successfully treated with radiotherapy after many failed attempts with surgery and chemotherapy.