Radiotherapy for Advanced Esophageal Cancer: from Palliation to Curation.

OPINION STATEMENT: Esophageal cancer is a global health problem, which is 7th most common and 6th most deadly cancer. It has been the era of immuno-oncology for esophageal cancer management. Radiation therapy has been one of the key local therapeutic approaches for esophageal cancer treatment, while its role in advanced disease is challenging and debatable. There have been emerging clinical and translational studies of radiation therapy in recurrent or metastatic esophageal cancer. Immunotherapy has been established the standard care of 1st and 2nd line systemic therapies of advanced esophageal cancer, and the development of tumor immunity has opened a new chapter for the esophageal cancer radiation therapy. The current review will summarize the classic radiation therapy research in advanced esophageal cancer, as well as the most recent key findings. The subtitles will cover palliative radiotherapy for dysphagia, re-radiation for recurrent disease, oligo-focal disease management and stereotactic radiation therapy, and radiotherapy with immunotherapy. Radiotherapy plays vital role in multidisciplinary management of advanced EC. External or intratumoral irradiation has been used for palliation of dysphagia and improving QOL in esophageal cancer patients traditionally, while recent clinical and technical advance enables radiotherapy to be considered in recurrent or metastatic disease for curation attention. Novel clinical and translational investigation is opening a new chapter of radiotherapy with immunotherapy for benefiting advanced EC patients.

Reirradiation with IMRT for recurrent head and neck cancer: A single-institutional report on disease control, survival, and toxicity.

AIM: To study and explores the feasibility and efficacy of re-irradiation (Re-RT) for locally recurrent head and neck cancer (HNC) and second primary (SP) malignancies. BACKGROUND: The most common form of treatment failure after radiotherapy (RT) for HNC is loco-regional recurrence (LRR), and around 20-50% of patients develop LRR. Re-irradiation (Re-RT) has been the primary standard of care in the last decade for unresectable locally recurrent/SP HNC. MATERIALS AND METHODS: It was a retrospective analysis in which we reviewed the medical records of 51 consecutive patients who had received Re-RT to the head and neck region at our institute between 2006 and 2015. RESULTS: Forty-eight patients were included for assessment of acute and late toxicities, response evaluation at 3 months post Re-RT, and analyses of locoregional control (LRC) and overall survival (OS). The median LRC was 11.2 months, and at 2 and 5 years the LRC rates were 41% and 21.2%, respectively. A multivariate analysis revealed two factors: initial surgical resection performed prior to Re-RT, and achievement of CR at 3 months after completion of Re-RT to be significantly associated with a better median LRC. The median OS was 28.2 months, and at 1, 2, and 5 years, OS were 71.1%, 55.9% and 18%, respectively. A multivariate analysis revealed initial surgical resection performed prior to Re-RT, and achievement of CR at 3 months post completion of Re-RT being only two factors significantly associated with a better median OS. Acute toxicity reports showed that no patients developed grade 5 toxicity, and 2 patients developed grade 4 acute toxicities. CONCLUSION: Re-RT for the treatment of recurrent/SP head and neck tumors is feasible and effective, with acceptable toxicity. However, appropriate patient selection criteria are highly important in determining survival and treatment outcomes.

Primary soft tissue sarcoma breast with multiphenotypic differentiation.

Primary soft tissue sarcomas of the breast are rare aggressive neoplasms. These often are misdiagnosed with other more common neoplasms like fibroepithelial malignancies, namely phyllodes tumour and metaplastic carcinoma. Being uncommon, chances of being misdiagnosed are higher leading to early mortality. A multidisciplinary team incorporating surgery, pathology, chemotherapy and radiotherapy is required to formulate an approach to primary soft tissue sarcoma. Generally, these tumours may show single or dual phenotype; we present one rare case report showing multiphenotypic differentiation.

Multi-modality management of chondrosarcoma of scapula: A case report and review of literature.

Chondrosarcoma are malignant tumours in which neoplastic cells produce cartilage. The most commonly affected sites are pelvis, femur, humerus and ribs. Scapula involvement is relatively rare. Surgery remains the primary modality of treatment for chondrosarcoma. Radiotherapy is used as an adjuvant therapy in high grade tumours and in cases of residual disease. Present study reports a rare case of scapular chondrosarcoma in a 37 year old male, managed with multimodality treatment and discusses briefly the prognostic parameters and treatment modalities. Only few studies have discussed about scapular chondrosarcoma and more studies with larger number of patients are needed to develop an evidence-based treatment and follow-up protocol for these patients.

Comparison of sequential versus simultaneous integrated boost of volumetric modulated arc therapy in treatment of oropharyngeal carcinoma.

OBJECTIVE: Volumetric modulated arc therapy (VMAT) is a useful treatment technique that can reduce treatment time while producing improved dose distribution to target structures. The main aim of the study is to evaluate the outcome of oropharyngeal cancer patients treated with VMAT, sequential (SEQ) versus simultaneous integrated boost (SIB) technique in terms of survival and failures and to assess late radiation toxicities with their dosimetric parameters. MATERIAL AND METHODS: Total 54 patients of histologically proved oropharyngeal cancer patients treated by definitive radiotherapy using VMAT technique in January 2019 to December 2020 were followed up and evaluated in terms of survival, patterns of failure and late radiation toxicities by RTOG toxicity criteria. RESULTS: After a median follow up of 12 months, overall survival (OS) and disease free survival (DFS) were 64.8% and 48.1% respectively. In terms of patterns of failure, 44.4% showed local recurrence, 7.4% as regional relapse and 3.7% showed distant metastasis. While comparing sequential versus SIB, no significant difference was found in OS (64.9% vs. 59.8%, p = 0.689), DFS (52.8% vs. 35.3%, p = 0.266), local control (LC) (58.3% vs. 47.1%, p = 0.437) and regional control (RC) (94.3% vs. 88.2%, p = 0.151) respectively. Among late radiation toxicities, the most common were xerostomia (42.2% for SEQ and 24.2% for SIB group), dysphagia (33.3% for SEQ and 15.1% for SIB group) and hoarseness of voice (15.1% for SEQ and 12.1% for SIB group). CONCLUSION: SIB technique proved better than SEQ technique in terms of pattern of failure or late toxicity, but no significant difference can be reported.

Challenges Faced by Cancer Patients in Receiving Health Services During the COVID-19 Pandemic in a Tertiary Care Hospital in Rajasthan.

BACKGROUND: Amidst the COVID-19 pandemic, cancer patients may have faced difficulty accessing health care. This study explored the challenges experienced by cancer patients in availing of healthcare during the pandemic, as well as the vaccination status and prevalence of COVID-19 infection among cancer patients in the year 2021. METHOD: A cross-sectional study was conducted in a tertiary care hospital in Jodhpur, Rajasthan, to interview 150 patients from the oncology department using convenience sampling. Face-to-face interviews lasted for 20-30 minutes. The first segment of the pretested semi-structured questionnaire was directed at obtaining the patient's socio-demographic characteristics, while the second segment focused on the problems that patients encountered during the pandemic in receiving cancer care. The data were analyzed using Statistical Packages for Social Sciences (SPSS) software (IBM Corp., Armonk, NY). RESULTS: Several constraints, such as a lack of transportation services, difficulty in availing outpatient department (OPD) and teleconsultation services, long waiting times, and deferred surgeries and therapies, have hampered cancer care. COVID-19 mitigation measures further imposed additional stress and financial burden on cancer patients. Moreover, there was low vaccination coverage among cancer patients, which increases their probability of acquiring an infection. CONCLUSION: Policy reforms must prioritize cancer care in India to maintain a continuum of care by ensuring medication, teleconsultation, uninterrupted treatment, and complete vaccination to decrease the risk of COVID-19 infection and facilitate patient compliance with the healthcare delivery system.

Is Hypoglycemia Secondary to Metastatic Retroperitoneal Sarcoma - A Therapeutic Challenge? Case Report and Review of Literature.

Most soft tissue sarcomas afflict the extremities; however, the retro peritoneum can also be affected rarely. Retroperitoneal sarcomas are relatively asymptomatic. Although tumor-induced hypoglycemia is rare in tumors other than insulinomas, extrapancreatic tumors are a subset that displays this phenomenon. The occurrence of hypo-insulinemic hypoglycemia with low GH and IGF-1 should prompt consideration of the secretion of a hypoglycemic substance impeding the secretion of insulin and GH, such as IGF-2 or one of its related substances. The present case report is of a 38-year-old male with retroperitoneal round cell sarcoma with liver metastasis with severe symptomatic hypoglycemia who was managed with multipronged symptomatic therapy and oncological management after which he had shown significant improvement in hypoglycemic episodes and symptom profile. A literature review revealed our case report to be the first reported case of a young male (preponderance in the older population) with hypoglycemia associated with retroperitoneal sarcoma which presented with liver metastasis and the only one treated with Gemcitabine /Docetaxel. The presence of these features might point toward a poorer prognosis in a disease with an already dismal course. All these points towards the need for further research regarding intensified oncological treatment after evidence-based prognostication of high-risk groups and modalities for the management of symptomatic hypoglycemia such as Somatostatin analogs and glucagon which aid in symptom control.

Assessment of knowledge, attitude, practices and distress level of cancer patients in COVID-19 pandemic: A cross-sectional study.

The diagnosis and treatment of cancer can be an extremely stressful experience for the patient. COVID-19 pandemic has further created an environment of stress and anxiety amongst cancer patients. A cross-sectional study was conducted from March 2020 to May 2020 using google forms to assess the knowledge, distress level, practices, and attitude toward the COVID-19 pandemic in cancer patients. It was observed that the females and elderly patients (> 55 years) were more knowledgeable about the COVID-19 pandemic. Also, females were more prone to emotional stress compared to males. While the younger age group (18-35 years) had a more hard time in dealing with family-related issues compared to other age groups. Therefore, the younger age group (18-35 years) and female gender being more prone to distress, warrant more attention from health care staff and caretakers. Moreover, the study highlights the need for mental and general health screening and intervention to balance the oncological care and COVID-19 situation.

Combined Modality Management of Sinonasal Anaplastic Lymphoma Kinase-Positive Anaplastic Large Cell Lymphoma in a Young Adult-Report of a Rare Case.

Sinonasal anaplastic lymphoma kinase (ALK)-positive anaplastic large cell lymphoma (ALCL) without nodal involvement is extremely rare and the rarity of this tumor often leads to diagnostic dilemma. It has been predominantly reported in pediatric, adolescent and young adult patients, mostly of Asian origin. A 21-year-old female patient presented with history of epistaxis for 1 year. On clinical and radiological examination, there was a 5 cm mass in the right nasal cavity, ethmoid, and frontal sinus. Biopsy at a local center had shown moderately differentiated squamous cell carcinoma. Rebiopsy at our center showed possibility of a hematolymphoid malignancy(pancytokeratin-, CD45+, CD3-, CD20-) and further immunohistochemistry studies(CD4+, CD43+, CD30+, ALK+) revealed ALK-positive ALCL. Rest of the lymphoma work-up was essentially normal and she had stage IE disease. She was treated with a combination of four cycles of cyclophosphamide, hydroxydaunorubicin, vincristine, and prednisolone (CHOP) regimen followed by local radiotherapy (36 Gray/20 fractions/4 weeks) by three-dimensional conformal technique. She tolerated the treatment well without any severe toxicity and had complete clinical and radiological response. At last follow-up visit, 40 months from the initial diagnosis, she was alive and disease free. Sinonasal ALK-positive ALCL is a rare tumor, which can be effectively treated with a combination of multiagent CHOP/CHOP-like regimen and local conformal radiotherapy.

Cutaneous metastases from neuroendocrine carcinoma of the cervix-An unusual metastatic lesion from an uncommon malignancy.

Neuroendocrine carcinoma (NEC) is an uncommon and aggressive type of small cell cervical cancer. NECs mostly arise from gastro-entero-pancreatic tract and the lung, but rarely from other organs like cervix. NEC of the cervix is a rare malignancy and constitutes 0.9%-1.5% of cervical tumors. NECs of cervix are common in perimenopausal females and present with abnormal vaginal bleeding and mimic squamous cell cancers, usually with no distinguishing features. On Immunohistochemistry, presence of chromogranin, synaptophysin, and CD-56 is necessary to make a diagnosis of small cell carcinoma. These tumors are notorious for local as well as distant relapses in comparison to their squamous and adenocarcinoma counterpart. NECs are characterized by highly aggressive clinical behavior and carry a poor prognosis. They commonly metastases to lung, liver, brain, and bones even in early stages of the disease. Metastasis to skin is a rare occurrence. We herein report a case of a NEC of the uterine cervix with multiple cutaneous metastases. After the initial diagnosis of NEC of cervix, the patient received concurrent chemoradiation followed by intracavitary brachytherapy. On subsequent follow-up, the patient developed multiple cutaneous metastasis along with liver metastases. This case is reported in view of rarity of the case with skin metastases. To the best of our knowledge, only 3 cases of cutaneous metastases from NEC of the cervix are reported till date. Being a rare malignancy, evidence in the literature is in form of case reports and small case series. Thus, the optimal treatment strategy varies for these patients. Multimodality management with teamwork is necessary to manage individual patients.

Malignant peripheral nerve sheath tumor of the tongue with an unusual pattern of recurrence.

Malignant peripheral nerve sheath tumor (MPNST) of oral cavity is an extremely uncommon malignancy. Less than 15 cases have been reported since 1973 though none of them describes a distant metastasis. We present a rare case of MPNST of the tongue who presented with features of hypoglossal nerve palsy. Incisional biopsy showed a malignant spindle cell tumor in the sub-epithelial connective tissue. The tumor cells were immune-positive for S-100. He underwent surgery followed by adjuvant chemo-radiation. Later the disease recurred in the form of isolated pelvic bone metastasis. Palliative chemotherapy was offered to him. With this case report we intend to refer to such unusual presentation and pattern of recurrence in a MPNST of tongue.

Extrarenal Extracranial Rhabdoid Tumor of the Pelvis in a Young Adult-management of a Challenging Case.

Rhabdoid tumor commonly occurs in the kidney and has an aggressive clinical course with high mortality. Central nervous system is the most common extrarenal site. Extrarenal extracranial rhabdoid tumor (EERT) is rare. EERT usually presents in childhood, and presentation in adulthood is extremely rare. This tumor is often difficult to diagnose, and there is no established standard of care due to the paucity of cases. We herein report a case of extrarenal rhabdoid tumor of the pelvis in a young adult and discuss the presentation and possible treatment options of this rare tumor.

Burden of preventable cancers in India: Time to strike the cancer epidemic.

India has a rapidly growing population inflicted with cancer diagnosis. From an estimated incidence of 1.45 million cases in 2016, the cancer incidence is expected to reach 1.75 million cases in 2020. With the limitation of facilities for cancer treatment, the only effective way to tackle the rising and humongous cancer burden is focusing on preventable cancer cases. Approximately, 70% of the Indian cancers (40% tobacco related, 20% infection related and 10% others) are caused by potentially modifiable and preventable risk factors. We review these factors with special emphasis on the Indian scenario. The results may help in designing preventive strategies for a wider application.

Primary Intraosseous Malignant Peripheral Nerve Sheath Tumor of Metacarpal Bones of the Hand in a Patient Without Neurofibromatosis 1: Report of a Rare Case.

Malignant peripheral nerve sheath tumor (MPNST) usually arises in peripheral nerve sheath cells. The intraosseous location of MPNST is rare. Mandible is the most common site of bony involvement. Involvement of bones of the hand is quite unusual. We report a case of MPNST involving metacarpal bones of the left hand treated with surgery followed by adjuvant radiation and chemotherapy and review the pertinent literature.

Comparative Study of Adjuvant Temozolomide Six Cycles Versus Extended 12 Cycles in Newly Diagnosed Glioblastoma Multiforme.

INTRODUCTION: Studies have shown promising survival with the use of Extended Temozolomide (E-TMZ) as compared to Conventional six cycles of Temozolomide (C-TMZ) in malignant gliomas; however, the reports are mostly limited to retrospective studies with significant bias. AIM: This study assesses the impact of six versus 12 cycles of adjuvant Temozolomide (TMZ) on Overall Survival (OS) in newly diagnosed postoperative patients of Glioblastoma Multiforme (GBM). MATERIALS AND METHODS: Between January 2012 and July 2013, 40 postoperative patients of GBM between age 18-65 years and Karnofsky Performance Score (KPS) ≥70 were included. Patients were randomized to receive radiation (60 Gray in 30 fractions over six weeks) with concomitant TMZ (75 mg/m2/day) and adjuvant therapy with either six (C-TMZ arm) or 12 cycles (E-TMZ arm) of TMZ (150-200 mg/m2 for five days, repeated four weekly). Twenty patients were treated in each arm. Toxicity was assessed using Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. OS and Progression Free Survival (PFS) were calculated from the time of diagnosis. Kaplan Meier method was used for survival analysis. A p-value of <0.05 was taken as significant and SPSS version 12.0 was used for all statistical analysis. RESULTS: Median number of adjuvant TMZ cycles was six and 12 in C-TMZ and E-TMZ arm respectively. Overall, 5% and 15% patients respectively in C-TMZ and E-TMZ arm had haematological toxicity ≥ 3 in grade. Median follow up in C-TMZ and E-TMZ arm were 14.65 months and 19.85 months. Median PFS was 12.8 months and 16.8 months in C-TMZ and E-TMZ arm respectively (p=0.069). Median OS was 15.4 months vs. 23.8 months in C-TMZ and E-TMZ arm respectively (p=0.044). CONCLUSION: Our study showed that E-TMZ is well tolerated and leads to a significant increase in PFS as well as OS in newly diagnosed patients of GBM. Further prospective randomized studies are needed to validate the findings of our study.

Comparison between weekly cisplatin-enhanced radiotherapy and cetuximab-enhanced radiotherapy in locally advanced head and neck cancer: first retrospective study in Asian population.

AIM: To present a direct comparison between chemotherapy-enhanced radiotherapy (CERT) and biotherapy-enhanced radiotherapy (BERT) in locally advanced head and neck cancer. METHODS: It is a retrospective analysis of 53 patients with locally advanced head and neck cancer treated from August 2006 to December 2008. For CERT, patients received weekly cisplatin (40 mg/m2 ) and for BERT, a loading dose of 400 mg/m2 of cetuximab given one week prior to radiotherapy followed by 250 mg/m2 given weekly along with radiotherapy. Disease-free survival (DFS) and overall survival (OS) were computed with Kaplan-Meier curve with log-rank test for comparison between the two groups. Multivariate Cox proportional hazards regression analysis was performed to estimate the impact of known relevant prognostic factors on DFS and OS. RESULTS: The median DFS was significantly better with CERT than BERT group (50.82 vs 11.66 months; P = 0.031). The 3 years DFS was significantly higher in CERT group than in BERT group (60.0% vs 14.3%; P = 0.022). The median OS was significantly better with CERT than BERT group (53.61 vs 32.55 months; P = 0.044). The 3 years OS was also significantly higher in CERT group than in BERT group (74.0% vs 42.1%; P = 0.032). There were no significant differences in acute toxicities of all grade and grade ≥3 between the two groups. The compliance to treatment and assisted feeding dependency for more than 6 months duration were also not significantly different. CONCLUSION: CERT is associated with better outcome with no significantly increased acute toxicities compared to BERT.

Retrospective analysis of treatment outcomes following reirradiation in locoregionally recurrent head and neck cancer patients: A single institutional study.

AIM: To present a retrospective analysis of treatment outcomes following reirradiation in locoregionally recurrent head and neck cancer patients at our institute. METHODS: Thirty-one patients of head and neck cancer who presented with a locoregional recurrence from April 2007 to April 2012 underwent salvage reirradiation. Median dose of first-time radiation was 70 Gy. Median duration of gap between the first and second course of radiation was 45.6 months. The median dose of reirradiation was 60 Gy. Conformal radiotherapy technique in the form of intensity modulated radiotherapy was used in 60% (17) of patients. Fourteen patients received concurrent chemotherapy or immunotherapy. RESULTS: After a median follow-up of 20.6 months, 12 patients were alive with no evidence of disease. The 3-year disease-free survival and overall survival were 28.7 and 48.5%, respectively. Acute and late toxicities were reported in 29 and 61% of patients, respectively. Severe grade 3 and 4 late complications were observed in nine patients but none of them led to mortality. CONCLUSION: Reirradiation appears to be both feasible and well tolerated in patients treated with previous radiotherapy for recurrent and second primary head and neck cancer. Careful case selection for reirradiation based on patient's performance status and tumor characteristics is essential.

Radiation-induced dental caries, prevention and treatment - A systematic review.

Treatment of head and neck cancers (HNCs) involves radiotherapy. Patients undergoing radiotherapy for HNCs are prone to dental complications. Radiotherapy to the head and neck region causes xerostomia and salivary gland dysfunction which dramatically increases the risk of dental caries and its sequelae. Radiation therapy (RT) also affects the dental hard tissues increasing their susceptibility to demineralization following RT. Postradiation caries is a rapidly progressing and highly destructive type of dental caries. Radiation-related caries and other dental hard tissue changes can appear within the first 3 months following RT. Hence, every effort should be focused on prevention to manage patients with severe caries. This can be accomplished through good preoperative dental treatment, frequent dental evaluation and treatment after RT (with the exception of extractions), and consistent home care that includes self-applied fluoride. Restorative management of radiation caries can be challenging. The restorative dentist must consider the altered dental substrate and a hostile oral environment when selecting restorative materials. Radiation-induced changes in enamel and dentine may compromise bonding of adhesive materials. Consequently, glass ionomer cements have proved to be a better alternative to composite resins in irradiated patients. Counseling of patients before and after radiotherapy can be done to make them aware of the complications of radiotherapy and thus can help in preventing them.

Planning and response to the influenza A (H1N1) pandemic: ethics, equity and justice.

This paper aims to highlight three ethical considerations related to influenza pandemic planning and response: ethical allocation of scarce resources; obligations and duties of healthcare workers to treat patients, and the balance between conflicting individual and community interests. Among these, perhaps the most challenging question facing bioethics is how to allocate scarce, life-saving resources given the devastating social and economic ramifications of a pandemic. In such situations, the identification of clear overall goals for pandemic planning is essential in making difficult choices. The dilemma between the duty to save patients and the right to protect the healthcare personnel's own life and health is a key issue. During the course of a pandemic, civil liberties may also be threatened, requiring limits on individual freedom to protect individuals as well as entire communities. Yet, individual liberty should be restricted with great care, and only when alternative approaches are not effective. Pandemic influenza planning and response should be a cooperative and shared responsibility that balances community and individual interests.