Extent of extravasation: Patients on parenteral plant alkaloids.

BACKGROUND: Plant alkaloids remain an essential part of many chemotherapeutic regimens. Although many adverse effects have been studied with appropriate management guidelines, extravasation (EV) is one adverse event that is yet to be studied at a regional scale to frame population-specific guidelines. METHODOLOGY: A hospital-based observational study was done for 1 year to understand the extent of extravasation among patients on parenteral plant alkaloids. Clinical pharmacists congregated information about patients satisfying the study criteria. The incidence of EV injuries associated with parenteral plant alkaloids was assessed. The severity was scored using the Common Terminology Criteria for Adverse Events (CTCAE) v4.3. The ESMO-EONS guidelines were followed for the classification of chemotherapeutic agents as well as management of the incidents of EV. RESULTS: Among the 80 patients recruited into the study, 26.25% of patients experienced EV injuries, of which 66.67% were grade 2 and 33.33% were grade 3. Females were prevalent at 62% among the injured group. Patients in the age group 31-50 years and 51-60 years sustained 28.57% of the injuries each. In 76.19% of injured patients, ambulation status was positive during the infusion. ESMO-EONS drug classification showed that 54.84% of the drugs prescribed were vesicants. Paclitaxel was seen in 33.33% of prescriptions in the injured group, among other plant alkaloids. CONCLUSION: Our study saw a trend of vesicant-induced extravasation injury among patients prescribed parenteral chemotherapeutic regimens with a combination of plant alkaloids, indicating the significant risk they may pose.

The limited use of autologous hematopoietic stem cell transplant for fit older patients with multiple myeloma in India: a retrospective analysis.

BACKGROUND: Multiple myeloma (MM) predominantly affects older patients; many of whom do not undergo autologous hematopoietic stem cell transplant (AHSCT) despite the associated survival benefits. This study was conceived to investigate the patterns of AHSCT among MM patients with due regard to their age and standardized fitness assessments. METHODS: Fitness scores as per the hematopoietic stem cell transplant-comorbidity index (HSCT-CI) and risk scores as per the revised-myeloma comorbidity index (R-MCI) of MM patients treated between January 2017 and December 2019 were analyzed to assess fitness for AHSCT. Proportions of patients who underwent AHSCT were calculated with regard to age and fitness for AHSCT. RESULTS: Of the 81 eligible patient records with a median age of 62 years, the HSCT-CI classified 79.6% and 77.8% of patients aged ≤65 years and >65 years as AHSCT eligible (p 1). Using the R-MCI, 96.3% and 81.5% of patients aged ≤65 years and >65 years, respectively, were classified as eligible for AHSCT (p 0.0381). Overall, patients aged ≤65 years underwent AHSCT with a greater frequency compared to those aged >65years (38.9 vs. 14.8%, p 0.0402). Irrespective of the age group, there was a statistically significant difference (p 0.0167) in terms of survival which favored those who underwent AHSCT. CONCLUSIONS: Both the HSCT-CI and the R-MCI revealed that nearly 80% of patients aged >65 years were fit enough to receive AHSCT. However, far fewer patients of this age group underwent AHSCT. We propose that the routine inclusion of objective fitness assessment could ensure that fit older patients undergo AHSCT and thus do not miss out on the benefits of the same.

Clinical Benefit of Comprehensive Genomic Profiling for Advanced Cancers in India.

PURPOSE: Comprehensive genomic profiling (CGP) assay is increasingly used in low-middle-income countries to detect clinically relevant genomic alterations despite its clinical benefits not being well known. Here, we describe the proportion of patients with advanced cancer in India who received targeted therapy for an actionable genetic alteration identified on CGP assays. METHODS: This was a multicenter, retrospective cohort study in adult patients with advanced nonhematologic malignancies who underwent a CGP test. If patients received a targeted therapy for ≥ 6 months, they were considered to have obtained a clinical benefit from the medication, whereas those continuing for ≥ 12 months were considered to have attained an exceptional response. Descriptive statistics were used to describe the proportion of patients with subsequent targeted therapy. RESULTS: During 2019-2020, 12 medical oncologists provided CGP reports for 297 patients; 221 met the inclusion criteria. Patients received a median of two lines (range: 0-5) of prior systemic therapy. On the basis of the CGP assay, 21 patients (10%) received targeted therapy. Among them, 33% was for human epidermal growth factor receptor 2 (HER2) amplification (nonbreast cancer) and 19% for HER2 or epidermal growth factor receptor exon 20 insertion mutation (lung cancer). After excluding patients with HER2 or epidermal growth factor receptor exon 20 insertions, 8% of 217 patients received targeted therapy. In the overall cohort of 221 patients, clinical benefit was seen in nine patients (4%), of whom two were exceptional responders (1%). CONCLUSION: We observed that in a low-middle-income country setting, 10% of patients received targeted therapy on the basis of CGP assay. Only 4% of patients who underwent CGP testing obtained a clinical benefit.

5-Fluorouracil induced extravasation injury.

Antineoplastic drugs based on their ability to cause local damage are classified as irritants, vesicants, and non-vesicants. Previous literature has reported higher rate of vesicants induced extravasation (EV) compared to irritants. We report the first case of irritant, 5-fluorouracil causing grade III EV in 55-year-old woman. The patient was diagnosed with esophageal squamous cell carcinoma. Docetaxel, Cisplatin, and 5-Fluorouracil (DCF) chemotherapy regimen was planned and administered through peripheral venous access. Patient experienced grade 3 extravasation in her 3rd cycle following 5-fluorouracil (5-FU) administration. The suspected drug was withdrawn immediately and discontinued from the 4th cycle of the regimen. The patient completely recovered from the symptoms of pain and erythema in the next cycle and care was taken not to infuse drug in the same site again. Since there is no appropriate antidote available to manage this condition, measures need to be taken to identify the predisposing factors for EV and prevent them.

A potential role for cyclophosphamide in the mitigation of acute respiratory distress syndrome among patients with SARS-CoV-2.

While humanity struggles to develop a vaccine against SARS-CoV-2, it is imperative that effective and affordable therapeutic strategies be evolved. Since a majority of the SARS-CoV-2 deaths are due to acute respiratory distress syndrome (ARDS), a strategy to mitigate the same could save countless lives. Since SARS-CoV-2 related ARDS has a strong immunological component, many investigators are utilizing monoclonal antibodies against IL-6, TNF-alpha and CCR5. However, targeting a single cytokine with an expensive monoclonal antibody could be a less pragmatic approach. We propose the use of cyclophosphamide as an immunomodulator, given its proven role in various settings including autoimmune diseases, and in the post-haploidentical stem cell transplant. Cyclophosphamide could deplete cytotoxic and effector T cell populations while relatively sparing the regulatory T cells (Tregs). Cyclophosphamide could tip the balance away from the overtly pro-inflammatory and could be a less expensive and effective alternative to the currently investigated monoclonal antibodies.

The future of lung cancer therapy: Striding beyond conventional EGFR and ALK treatments.

Lung cancer, one of the most frequently diagnosed cancers worldwide has long relied on testing for the molecular biomarkers EGFR/ALK. However, achieving superior clinical outcomes for patients with lung cancer requires developing comprehensive techniques beyond contemporary EGFR/ALK testing. Current technologies are on par with molecular testing for EGFR/ALK in terms of efficacy, most of them failing to offer improvements perhaps primarily due to skepticism among clinicians, despite being recommended in the NCCN guidelines. The present study endeavored to minimize chemotherapy-dependence in EGFR/ALK-negative patient cohorts, and use evidence-based methods to identify ways to improve clinical outcomes. In total, 137 lung cancer cases obtained from 'PositiveSelect NGS data', comprising 91 males and 46 females, were investigated. EGFR- and ALK-positivity was used for data dichotomization to understand the therapeutic utility of rare gene alterations beyond just EGFR/ALK. Statistics obtained from PositiveSelect were collated with data from international studies to construct a meta-analysis intended to achieve better clinical outcomes. Upon dichotomization, 23% of cases harbored EGFR variants indicating that treating with EGFR TKIs would be beneficial; the remaining 77% exhibited no EGFR variants that would indicate favorable results using specific currently available chemotherapy practices. Similarly, 28% of cases had EGFR+ALK variants favoring EGFR/ALK-based targeted therapeutics; the remaining 72% harbored no EGFR/ALK variants with known beneficial chemotherapy routes. The present study aimed to overcome current inadequacies of targeted therapies in patients with a conventional EGFR/ALK-positive diagnosis and those in EGFR+ALK-negative cohorts. Upon analysis of the negative cohorts, significant and clinically relevant single nucleotide variants were identified in KRAS, ERBB2, MET and RET, with frequencies of 7, 1, 2 and 3% in patients who were EGFR-negative and 6, 1, 1, and 3% in patients who were EGFR and ALK-negative, respectively, enabling the use of targeted therapeutics aside from EGFR/ALK TKIs. From the results of the current study only 35% of the two negative arms (EGFR negative and EGFR+ALK negative) would be recommended NCCN or off-label chemotherapy; prior to the current study, the entire cohorts would have been recommended this treatment. The present study emphasizes the potential of comprehensive genomics in identifying hallmarks of lung cancer beyond EGFR/ALK, using broad-spectrum genetic testing and data-sharing among medical professionals to circumvent ineffective chemotherapy.

Management of Hodgkin's lymphoma with midbrain involvement: A case report and review of literature.

Introduction Primary central nervous system (CNS) involvement of Hodgkin's lymphoma is very uncommon. There are only a few previous reports of Hodgkin's lymphoma of nodular lymphocyte predominant histology involving the CNS concurrently with systemic disease. Case presentation A 12-year-old boy with a history of painless left inguinal swelling and acute diplopia. There was an intensely enhancing lesion in the right midbrain on magnetic resonance imaging. The patient was diagnosed with stage IV Hodgkin's lymphoma of nodular lymphocyte predominance type by routine microscopy and immunohistochemistry of left inguinal lymph node biopsy with computed tomography-assisted staging. It was planned to treat him with six cycles of chemotherapy with intrathecal methotrexate, followed by radiotherapy to the CNS lesions. After two cycles of chemotherapy, the patient entered complete remission of all lesions including the CNS lesion documented by the positron emission tomography scan. Conclusion We are describing the course of this rare presentation of Hodgkin's lymphoma of nodular lymphocyte predominant histology involving the CNS and clinical challenge in its diagnosis and management of this case.

Relapsed Hodgkin's Lymphoma Presenting with Isolated Ulcerative Lesion on Base of Tongue.

INTRODUCTION: Primary extra nodal involvement of Hodgkin's lymphoma is very uncommon and previous reports of Hodgkin's lymphoma involving the base of tongue as isolated lesion in relapsed disease are few. CASE PRESENTATION: A 79-years male patient who has diagnosed and treated for stage IV Nodular sclerosis Hodgkin lymphoma 2 years back, now presented with isolated ulcerative lesion in base of tongue which was metabolically active on positron emission tomography scan, suspicious of recurrent disease and was confirmed by routine microscopy and immunohistochemistry of tissue biopsy. CONCLUSION: Extra nodal relapse at base of tongue was an uncommon clinical scenario in natural history of Hodgkin's lymphoma, which can present as an unexpected challenge for diagnosis and management. So we should be aware of this uncommon but unique presentation of Hodgkin's lymphoma.

Acute interstitial lung disease in a patient with anaplastic lymphoma kinase-positive non-small-cell lung cancer after crizotinib therapy.

Crizotinib, an orally active multi-targeted small-molecule anaplastic lymphoma kinase (ALK) inhibitor, is an effective treatment modality for advanced ALK-positive non-small-cell lung cancer (NSCLC). Most drug-related adverse events are mild to moderate; however, some patients may develop acute interstitial lung disease (ILD) which is sometimes fatal. We present a case of crizotinib-associated ILD in a 47-year-old woman treated with crizotinib for metastatic adenocarcinoma of the lung. The patient presented with acute breathlessness and hypoxaemia in the second month of crizotinib therapy; radiological and histopathological work-up was suggestive of acute interstitial pneumonia. The patient improved clinically with corticosteroid therapy and was successfully re-challenged with crizotinib. In conclusion, while treating NSCLC patients with crizotinib, it is important to promptly investigate and treat any new-onset respiratory symptoms, as the latter could represent an adverse effect related to therapy. Prompt discontinuation of the offending drug and initiation of corticosteroid therapy may prevent adverse outcomes.

Epidermal growth factor receptor inhibitors related trichomegaly of Eyelashes.

Advances in understanding of the mechanisms involved in oncogenesis have led to the development of targeted therapies such as epidermal growth factor receptor inhibitors (EGFRIs), targeting a variety of molecular structures and able to inhibit aberrantly activated oncogenic pathways. Their use made treatment more tolerable with significant reduction of systemic adverse effects. However, EGFRIs are associated with toxicities affecting the skin and adnexal structures that affect the majority of treated patients. Trichomegaly of eyelashes is a unique side-effect, seen in prolonged treatment with EGFRI. It is essential to be familiar with this adverse effect, its potential complications, long-term sequelae, and available effective treatment strategy in order to appropriately manage these patients.

A retrospective study of central venous catheters GCRI experience.

BACKGROUND: The use of central venous catheters (CVCs) has greatly improved the quality-of-care in cancer patients, yet these catheters may cause serious infectious and thrombotic complications. The aim of this retrospective study was to study the various types of CVCs and their complications. MATERIALS AND METHODS: We studied retrospectively 213 cases of CVCs in our institute with their indications, type and complications from August 2010 to July 2011. RESULTS: A total of 213 CVCs were inserted in patients with hematological (62%) and solid organ malignancies (38%). Ninety-eight patients (46%) had peripheral inserted central catheter (PICC), 90 (42%) patients had Hickman catheters and 25 (12%) had a port. The median duration of retention of Hickman catheters was 104 days (3-365 days), for the peripherally inserted central catheters was 59 days (3-100 days) and for the port it was 280 days (45-365 days). Non-infective complications were more than infective (12% vs. 7%). The most common complication was non-infective occlusion and thrombophlebitis. In one patient with PICC thrombosis occurred in the cephalic, radial and ulnar vein and in one patient with port thrombosis occurred in the superior vena cava. Organisms were isolated in 60% (12 out of 20) of cultures. Common organisms isolated were Pseudomonas aeruginosa in 5 (42%), Staphylococcus aureus in 2 (16%), Escherichia coli in 2 (16%) and Aspergillus in 3 (25%) patients. 7 out of 12 infected patients had negative blood cultures within 7 days of antibiotic treatment, 5 patients remained positive for more than 7 days with antibiotics. In 155 patients (73%), the desired treatment protocol was completed and at present there are still 28 patients (13%) with catheters. 5 patients (2.3%) died of febrile neutropenia and septicemia with multi-organ failure. In 5 patients (2.3%), the catheters (1 Port, 1 Hickman and 3 PICC) were prematurely removed because of thrombosis. CONCLUSION: CVCs are better options to facilitate the long-term vascular access provided infection is prevented with meticulous care and treated promptly with proper antibiotics. Most CVCs is acceptable to patients.