Primary squamous cell carcinoma of thyroid gland-First case report from state Punjab, India.

Primary squamous cell carcinoma of the thyroid is a very rare thyroid malignancy. In addition, due to its presentation as a locally advanced disease with a high tendency to metastasize, it has a poor prognosis and outcome. We report a 60-year-old male patient with PSCC, which was confirmed by immunohistochemistry on biopsy. The patient was staged as T4N1M0 and was planned as per the multidisciplinary team approach. In sum, pathologic examination and IHC aid in distinguishing this lesion and help in differentiating it from other tumors of similar histology. Furthermore, it also aids in planning treatment.

Practical Clinical Consensus Guidelines for the Management of Cancer Associated Anemia in Low- and Middle-Income Countries.

Purvish M. ParikhCancer-associated anemia (CAA) remains a major unmet need that compromises overall survival (OS) and quality of life (QoL). Currently, available guidelines do not take into consideration the unique challenges in low- and middle-income countries (LMIC). Our CAA patients have to battle preexisting impaired nutritional status, depleted body iron stores, financial limitations, and difficulty in having easily accessible affordable healthcare. Hence, we fulfilled the need of guidelines for LMIC. A group of subject experts were put together, given background literature, met in a face-to-face discussion, voted using Delphi process, and finally agreed on the contents of this guideline document. As many as 50% of cancer patients will have significant anemia (hemoglobin < 10 g/dL) at initial diagnosis. It is most commonly seen with gastrointestinal malignancies, head and neck cancers, and acute leukemias. The hemoglobin falls further after initiation of cancer directed therapy, due to chemotherapy itself or heightened nutritional deficiency. Its evaluation should include tests for complete blood count, red blood cell morphology, reticulocyte count, Coombs test, and levels of vitamin B12 and folic acid. Iron status should be monitored using test to measure serum iron, total iron binding capacity, transferring saturation, and serum ferritin levels. A minimum of 50% of cancer patients with anemia require iron supplements. The preferred mode of therapy is with intravenous (IV) iron using ferric carboxymaltose (FCM). Most patients respond satisfactorily to single dose of 1000 mg. It is also safe and does not require use of a test dose. Significant anemia is found in at least half of all cancer patients in India, South Asian Association for Regional Cooperation region, and other LMIC countries. Its awareness among healthcare professionals will prevent it from remaining undiagnosed (in up to 70% of all cancer patients) and adversely affecting OS and QoL. The benefits of treating them with IV iron therapy are quick replenishment of iron stores, hemoglobin returning to normal, better QoL, and avoiding risk of infections/reactions with blood transfusions. Many publications have proven the value of single-dose FCM in such clinical situations. CAA has been proven to be an independent prognostic factor that adversely affects both QoL and OS in cancer patients. Use of FCM as single IV dose of 1000 mg is safe and effective in the majority of patients with CAA.

Excellent Response to Full-Dose 177 Lu-PSMA-617 RLT in Metastatic Castration-Resistant Prostate Cancer With Transplant Kidney : A Step Ahead.

ABSTRACT: 177 Lu-PSMA radioligand therapy (RLT) has shown very encouraging results in metastatic castrate-resistant prostate cancer (mCRPC) patients with acceptable adverse events. The adverse events of RLT are mainly limited to salivary glands and kidneys. However, there is dearth of available data of RLT in transplanted kidney patients with mCRPC. Here is a case of 68-year-old mCRPC patient with history of renal transplant who underwent 4 cycles of 177 Lu-PSMA-617 RLT (~7.4 GBq/cycle). Posttherapy serum creatinine and glomerular filtration rate remained stable along with excellent response and symptomatic improvement, thus demonstrating the safety of full dose of 177 Lu-PSMA in renal transplant patients.

Pembrolizumab-Induced Lichen Planus: A Rare Immune-Related Adverse Side Effect.

Pembrolizumab is the first anti-programmed death protein-1 agent approved by the US Food and Drug Administration. It has demonstrated efficacy in melanoma, lung cancer, and other advanced solid tumours and hematologic malignancies. Various dermatological side effects including pruritus, maculopapular rash, vitiligo, lichenoid skin reactions, psoriasis, and rarely life-threatening conditions like bullous pemphigoid, Stevens-Johnson syndrome, and drug rash with eosinophilia and systemic symptoms have been reported. We report a case of pembrolizumab-induced lichen planus in a 54-year-old female who was receiving pembrolizumab for management of lung metastasis from squamous cell carcinoma of the buccal mucosa. The lichen planus responded to acitretin and pembrolizumab was continued safely.

Autologous stem cell transplantation for multiple myeloma in the novel agent era: Systematic review of Indian data and implications for resource constrained settings.

Treatment of multiple myeloma has undergone significant advances in the last two decades, leading to meaningful improvement in overall and progression free survival. The incurable nature of disease necessitates serial sequencing of treatment options and continuous therapy once disease remission is achieved. Autologous stem cell transplantation (ASCT) has continued to offer a meaningful survival advantage with a consistent reduction in toxicity and costs. Despite the advent of newer drugs leading to deeper and sustained responses, ASCT continues to be the standard of care for all eligible patients and is ostensibly more cost effective than continued treatment with newer agents. However, ASCT continues to be underutilized in India, due to concerns about cost, safety, and sporadic expertize. We present a systematic review of available data on ASCT for multiple myeloma from India to evaluate safety and efficacy of the procedure, and provide evidence re-affirming its utility in resource constrained settings.

Distinctive Attributes of Indian Patients With Classical BCR::ABL1 Negative Myeloproliferative Neoplasms: Unified Clinical and Laboratory Data.

INTRODUCTION: We report one of the largest single center data from a mixed referral setting in India describing baseline characteristics and outcomes of patients with classical BCR::ABL1 negative myeloproliferative neoplasms (MPNs). MATERIALS AND METHODS: Patients diagnosed from June 2019 to 2022 were included. Workup and treatment was as per current guidelines. RESULTS: Diagnosis comprised polycythemia vera (PV) in 51(49%), ET in 33(31.7%) and prefibrotic primary myelofibrosis (MF) pre fibrotic myelofibrosis (prePMF) and myelofibrosis in 10(9.6%) patients each. Median age at diagnosis was 52 years for PV and ET, 65.5 for MF and 79 years for prePMF. Diagnosis was incidental in 63(56.7%) and after thrombosis in 8(7.2%) patients. Baseline next generation sequencing (NGS) was available for 63(60.5%) patients. Driver mutations in PV: JAK2 in 80.3%; in ET: JAK2 in 41%, CALR in 26%, MPL in 2.9%; in prePMF JAK2 in 70%, CALR in 20%, MPL in 10%, and in MF: JAK2 in 10%, MPL in 30% and CALR in 40%. Seven novel mutations were detected of which 5 were potentially pathogenic on computational analysis. After median follow up of 30 months, 2 patients had disease transformation and none had new episodes of thrombosis. Ten patients died, most commonly with cardiovascular events(n = 5,50%). Median overall survival was not reached. Mean OS time was 10.19 years(95%CI, 8.6 to 11.74) and mean time to transformation was 12.2 years(95% CI,11.8 to 12.6). CONCLUSION: Our data indicates comparatively indolent presentation of MPNs in India with younger age and lower risk of thrombosis. Further follow up will enable correlation with molecular data and guide modification of age based risk stratification models.

Isolated pancreatic myeloid sarcoma: A potential mimicker of pancreatic adenocarcinoma.

Myeloid sarcoma (MS) is an extramedullary proliferation of immature myeloid cells which may occur as a progression of myelodysplastic syndrome (MDS), myeloproliferative neoplasm (MPN), or myelodysplastic syndrome/myeloproliferative neoplasm (MDS/MPN) and as acute myeloid leukemia (AML) relapse. Rarely may it be de novo. Lymph nodes, skin, lungs, intestine are the commonly involved sites. However, an isolated pancreatic MS is seldom reported in the literature. Herein, we report one such case which was misdiagnosed as pancreatic adenocarcinoma on the clinico-radiological examination which misled us away from preoperative diagnostic sampling, and a Whipple pancreaticoduodenectomy was performed. Histopathological examination in conjunction with immunohistochemistry revealed the final diagnosis of isolated MS of the pancreas. We emphasize that although rare, a clinical suspicion along with preoperative histopathological examination may lead to early diagnosis, targeted management, and a better clinical outcome in such cases.

Prevalence of Molecular Subtypes in Operated Cases of Breast Cancer and Its Clinicopathological Correlation: A Single Institute Study from a Tertiary Cancer Centre in North India.

Breast cancer has emerged as a major health problem among women in India. There are few Indian studies which have looked at prevalence of molecular subtypes of breast cancer in Indian population. The primary objective of our study was to find out the prevalence of various molecular subtypes in operated cases of breast cancer patients presenting to us. Three hundred sixty patients who were operated in our department were analysed. Clinicopathological features of all cases were recorded. Classification into various molecular subtypes was done using St. Gallen 2013 criteria. Luminal B HER2 negative was the predominant molecular subtype in our study population constituting 30.3% of patients. The percentage of aggressive subtypes, viz. triple negative breast cancer and HER2 enriched, were 21.7% and 11.4% respectively. Only 19.4% of patients in our study population had tumour size ≤ 2 cm with nodes being positive in 56.9% of our patients at presentation. Data from our study and other studies published from India show that the two most aggressive subtypes of, viz. triple negative breast cancer and HER2 enriched, may be more prevalent in our population as compared to western population.

Prognostic factor for recurrence in esophagus cancer patients who underwent surgery for curative intent: A single-institution analysis.

OBJECTIVE: The purpose of this study is to analyze predisposing factors for a higher risk of recurrence in esophageal cancer patient who underwent surgery for curative intent and to do survival analysis of prognostic factors. MATERIALS AND METHODS: Between February 2018 and March 2020, we retrospectively identified 28 cases staged T1b to T4a managed electively at our institute as per multidisciplinary management plan. Demographic, clinical, radiological, operative, histopathological parameters, upfront surgery done or not, type of preoperative, and adjuvant treatment used and whether neoadjuvant or adjuvant therapy was planned along with waiting time for surgery, were assessed as potential risk factors. End point of study was to find potential risk factors for recurrence and to do their subgroup survival analysis. RESULTS: The recurrence rate in our study was 25% with a mean follow-up of 24 months. The median time of recurrence was 8.5 months, all recurrence occurred within 1 year. Overall DFS at 2 years was 72%. On univariate analysis, following prognostic factors were associated with high risk of recurrence, male sex X2 (1) =4.42, p = 0.035; histology subtype of adenocarcinoma X2 (1) = 7.07, p = 0.008; margin positive X2 (1) =3.76, p = 0.05; presence of lymph vascular invasion (LVI) X2 (1) =7.88, p = 0.005; presence of perineural invasion (PNI) X2 (1) =5.97, p = 0.015; postoperative T size >4 cm X2 (1) =3.86, p = 0.049; and nodal positivity X2 (3) =13.47, p = 0.004. CONCLUSIONS: Male sex, adenocarcinoma histological subtype, positive resected margin, presence of LVI and PNI, postoperative T size >4 cm, and high postoperative nodal positivity and whether neoadjuvant versus adjuvant therapy given (on K. M analysis) were the identified predictors of recurrence which compromised DFS.

Thrombocytopenia in COVID-19: Focused Summary of Current Understanding of Mechanisms and Clinical Implications.

Thrombocytopenia is noted in corona virus disease-2019 (COVID-19) with a prevalence of 5% to 41%, and has been observed to be associated with inferior outcomes. The pathogenesis of thrombocytopenia in COVID-19 is unique and differs from other viral syndromes in terms of clinical presentation and causative mechanisms. Platelets act as both targets and the initial defense against severe acute respiratory syndrome-coronavirus 2 and work in concert with the underlying thrombophilic mechanisms to modulate the final disease phenotype. Understanding these mechanisms may possibly allow targeting of a key component of COVID-19 pathogenesis. We provide a focused review of the current mechanisms implicated in development of thrombocytopenia in COVID-19 and therapeutic implications of the same.

Risk Factors of Biochemical Failure in Locally Advanced Carcinoma Prostate Treated With Definitive External Beam Radiotherapy and Androgen Deprivation Therapy: Experience From Tertiary Care Center in North India.

Background Locally advanced prostate cancer (LACAP), despite external beam radiotherapy (EBRT) along with antiandrogen therapy (ADT) has risk of prostate-specific antigen (PSA) progression. Furthermore, number of studies have emphasized on different prognostic factors. The purpose of our study is to analyze risk factors for biochemical failure (BF) in these patients treated at our institute. Methods Our study is a single-institution retrospective observational done at a tertiary care center in North India. Between January 2018 and December 2020, we retrospectively identified 34 patients managed at our institute as per multidisciplinary board (MBD). Demographic, clinical, radiological, pathological and treatment-related parameters were assessed as potential risk factors. End-point of the study was to find significant risk factors for BF. Statistical analysis was done on SPSS, version 20 (IBM Corp., Armonk, NY). Results All eligible patients received EBRT with ADT as per institution policy. Mean follow-up period was 20 months during which two (5.9%) patients had BF at a mean of 30 months after EBRT. Four-year PSA-progression-free survival rate was 73%. On univariate analysis, prognostic factors associated with high risk of BF were Gleason score and clinical T stage. Conclusion In summary, prognostic factors for high risk of BF leading to clinical progression are Gleason score 9 or 10 and clinical T3b stage.

Mitigation of in-hospital risk of coronavirus disease 2019: Experience from a haematology-oncology and stem cell transplant setting.

Background: . Coronavirus disease 2019 (Covid-19) was first described in December 2019 and has evolved into an ongoing global pandemic. Cancer patients on chemotherapy are immunocompromised and are at the highest risk of Covid-19-related complications. We describe our experience with the management of haematology-oncology and stem cell transplant (SCT) patients receiving curative chemotherapy in a hospital with a high influx of Covid-19 patients. Methods: . We did a prospective observational study at a 99-bedded cancer centre of a tertiary care teaching hospital from April 2020 to September 2020. Preventive measures taken were categorized as follows: (i) staff: screening, mandatory use of personal protective equipment (PPE), risk stratification of potential exposure and testing and isolation as needed; (ii) patients: mandatory viral polymerase chain reaction testing, segregation of positive and untested patients and testing of family members; and (iii) environment: mandatory regular cleaning, visitor restriction, telemedicine services and reassignment of priority to clinic visits. Treatment of the underlying conditions was continued with added precautions. Results: . A total of 54 patients were included in the analysis, including 48 with haematological malignancies and 6 for stem cell therapy. Preventive measures were universally applied, and chemotherapy with a curative intent was initiated as per protocol. Three patients were detected to have Covid-19 infection before admission and one after the institution of chemotherapy. Nine patients died after the first cycle of chemotherapy, 2 due to severe Covid-19-related illness and 7 due to complications of chemotherapy or disease progression. Conclusions: . In the wake of the Covid-19 pandemic, treatment for haematological malignancies must continue while balancing the risk of Covid-19 infections. Our report emphasizes the effectiveness of measures such as hand hygiene, social isolation, patient segregation, use of masks and PPE and universal pre-treatment testing for Covid-19 in reducing the risk of infection in a high-risk clinical setting.

Clinical and Molecular Attributes of Patients With BCR/ABL1-negative Myeloproliferative Neoplasms in India: Real-world Data and Challenges.

INTRODUCTION: Classic BCR/ABL1-negative myeloproliferative neoplasms (MPNs) are characterized by clinical and genetic heterogeneity and include 4 distinct constituents. Very little data on clinical presentation and epidemiology of the same is available from the Indian setting. PATIENTS AND METHODS: Patients referred to Hematology-Oncology from January 2018 to August 2020 with suspected MPNs were included in the analysis and prospectively followed-up. All patients were initially screened, and only those meeting the updated World Health Organization 2016 criteria were included in the analysis. Epidemiologic, clinical, and molecular characteristics were documented, and patients were followed-up prospectively. RESULTS: A total of 233 patients were referred for evaluation of MPN, of which 63 were included in the analysis, including 39 males and 24 females. The median age at diagnosis was 57 years (range, 28-82 years), and 38% patients were younger than 50 years of age. The most common presentations were incidental detection in 35 (55.5%), abdominal symptoms in 13 (20%), fatiguability in 7 (11%), and recent vascular events in 6 (9.5%) patients. Final diagnosis was polycythemia vera in 27, essential thrombocytosis (ET) in 21, prefibrotic myelofibrosis in 9, and myelofibrosis in 6 patients. The frequency of driver mutations in polycythemia vera included JAK2 in 75%; in ET, JAK2 in 33%, CALR in 33%, and MPL in 4%; and in prefibrotic myelofibrosis, JAK2 in 66% and CALR in 33%. Aspirin was used for all patients along with risk-adapted cytoreduction with hydroxyurea. Ruxolitinib was reserved for symptoms refractory to hydroxyurea. After a median follow-up of 15 months (interquartile range, 10-28 months) from diagnosis, disease progression was noted in 4 patients. Two patients died at the end of the follow-up period, including 1 with secondary acute myeloid leukemia post myelofibrosis and one with ET and coexistent oral malignancy. The remaining 61 patients are alive and on regular treatment. RESULTS: This is one of the first systematic descriptions and prospective follow-up of patients with BCR/ABL-negative MPNs from India. Our study indicates a younger median age of presentation and higher proportion of JAK2-unmutated disease across all subtypes. The primary role of bone marrow morphology and supportive role of somatic mutations in differentiating MPN subtypes is indicated. CONCLUSIONS: This study sets the stage for a collaborative registry for defining epidemiologic data and long-term outcomes with MPN in India.

Treatment of Acute Leukemia During COVID-19: Focused Review of Evidence.

The Coronavirus disease-2019 (COVID-19) pandemic is an unprecedented health care crisis and has led to over 1.5 million deaths worldwide. The risk of severe COVID-19 and mortality is markedly raised in patients with cancer, prompting several collaborative groups to issue guidelines to mitigate the risk of infection by delaying or de-escalating immunosuppressive therapy. However, delayed therapy is often not feasible for patients requiring treatment for acute leukemia or stem cell transplantation. We provide a focused review of the recommendations and evidence for managing this high-risk group of patients while minimizing the risk of COVID-19 infection, and provide a small snapshot of treatment data from our center.

A tertiary care experience with paclitaxel and cetuximab as palliative chemotherapy in platinum sensitive and nonsensitive in head and neck cancers.

BACKGROUND: The combination of paclitaxel and cetuximab (PaCe) has led to an encouraging response rate in Phase 2 setting with limited toxicity. The aim of our study was to assess the efficacy of this regimen in our setting in platinum sensitive and nonsensitive patients. METHODS: This was a retrospective analysis of head and neck cancer patients treated with weekly PaCe as palliative chemotherapy between May 2010 and August 2014. The standard schedule of cetuximab along with 80 mg/m2 of weekly paclitaxel was administered till either disease progression or withdrawal of patient's consent. The toxicity and response were noted in accordance with CTCAE version 4.02 and RECIST version 1.1 criteria, respectively. The response rates between platinum sensitive and nonsensitive patients were compared by Chi-square test. Overall survival (OS) and progression-free survival (PFS) were estimated by Kaplan-Meier survival method and log-rank test was used for comparison. Cox proportional hazard model was used for identification of factors affecting PFS and OS. RESULTS: One Hundred patients with a median age of 52 years (interquartile range: 46-56 years) were included. Forty-five patients (45%) were platinum insensitive, whereas 55 patients (55%) were platinum sensitive. In platinum insensitive patients and sensitive patients, the response rates were 38.5% and 22.2%, respectively (P = 0.104), whereas the symptomatic benefit in pain was seen in 89.5% and 71.7%, respectively (P = 0.044). The median PFS in platinum insensitive and sensitive patients were 150 and 152 days, respectively (P = 0.932), whereas the median OS was 256 days (95% confidence interval [95% CI]: 168.2-343.8 days) and 314 days (95% CI: 227.6-400.4 days), respectively (P = 0.23). Nineteen patients (19%) had grades 3-4 adverse events during chemotherapy. CONCLUSION: Weekly paclitaxel combined with cetuximab has promising efficacy and good tolerability in the palliative setting in advanced head and neck cancer in both platinum sensitive and insensitive patients.

Personalized treatment approach to gastroenteropancreatic neuroendocrine tumors: a medical oncologist's perspective.

The medical management of gastroenteropancreatic neuroendocrine tumors involves treatment of symptomatic disease related to hormone secretions or bulky unresectable metastatic disease. Combining gallium DOTA with fluorine-18 fluorodeoxyglucose-PET along with histopathological grading helps to determine tumor heterogeneity and seek reasons for poor response to therapy. In the light of adding chemotherapy in selected patients with intermediate-grade tumors, the newer scan helps in personalization of the therapy along with the biopsy. The tumor dedifferentiation over the particular time period leading to aggressive behavior, a well-known entity, is contrasted with the redifferentiation phenomenon in some patients as a result of chemotherapy or targeted drug therapy. This may support the basis for combining peptide receptor-targeted radiotherapy/octreotide therapy with chemotherapy or mTOR inhibitors such as everolimus.

Neoadjuvant Imatinib in Locally Advanced Gastrointestinal stromal Tumours, Will Kit Mutation Analysis Be a Pathfinder?

INTRODUCTION: Longer duration of neoadjuvant (NA) imatinib (IM) used for locally advanced (LA) gastrointestinal stromal tumours (GIST) is not based on biology of the tumour reflected by kit mutation analysis. MATERIAL AND METHODS: LA or locally recurrent (LR) GIST treated with NA IM from May 2008 to March 2015 from a prospective database were included in the analysis. Archived formalin-fixed paraffin-embedded tissues (FFPE) were used for testing KIT exons 9, 11, 13 and 17 by PCR. RESULTS: One hundred twenty-five patients with LA or LR GIST were treated with NA IM. Forty-five patients (36 %) had undergone c-kit mutation testing. Exon 11 was seen in 25 patients (55.5 %), 3 with exon 9 (6.7 %) and 2 with exon 13 (4.4 %). Twelve were wild type (26.6 %) and  3 (6.7 %) were declared uninterpretable. Response rate (RR) for the exon 11 mutants was higher than the non-exon 11 mutant group (84 vs. 40 %, p = 0.01). Disease stabilization rate (DSR) rates were also higher in the exon 11 subgroup than non-exon 11 group (92 vs. 75 %). Eighty-four per cent exon 11 and 75 % non-exon 11 mutants were surgical candidates. Patients undergoing surgery had significantly improved event free survival (EFS) (p < 0.001) compared to patients not undergoing surgery, with the same trend seen in OS (p = 0.021). Patients with a SD on response to NA IM had a lower EFS (p = 0.076) and OS compared to patients achieving CR/PR. There were no differences between the various exon variants in terms of outcomes and responses CONCLUSION: Upfront evaluation of kit mutation status may help us in delineating separate treatment strategies for potentially biologically different tumours and assessing the correct timing of surgery for this subset of GIST.