Analysis of the effect of baseline detection and early clearance of ct-DNA, on survival outcomes among patients with advanced EGFR-mutant non-small cell lung cancer.

BACKGROUND: To determine if circulating tumor DNA (ct-DNA) dynamics of epidermal growth factor receptor (EGFR) mutation in plasma can identify a subset of patients with EGFR-mutant (EGFR- m) non-small cell lung cancer (NSCLC) with inferior survival outcomes, we analyzed and compared survival outcomes among patients with and without baseline presence and early clearance of EGFR ct-DNA in plasma. MATERIAL AND METHODS: For 66 patients newly dia-gnosed with EGFR- m NSCLC, plasma samples were collected at baseline and 1st response assessment at 12-24 weeks for extraction of ct-DNA. Estimation of ct-DNA (EGFR exons 18, 19, 20 and 21) was done using droplet digital polymerase chain reaction (dd-PCR) on the QX200 ddPCR system (BioRad, USA). Patients with detectable EGFR ct-DNA at baseline (sample 1), with either undetectable or persistent detectable ct-DNA in sample 2 were classified as clearers and non-clearers, respectively. RESULTS: Fifty-three patients received 1st/ 2nd generation EGFR tyrosine kinase inhibitors (TKIs) and 13 received either 3rd generation TKI (osimertinib) or chemotherapy plus gefitinib. The baseline ct-DNA-positive group had more patients with extra thoracic disease (60.4 vs. 48.5%). For the entire cohort, there was no difference in median progression-free survival (PFS) among baseline ct-DNA-negative (13.57 months) vs. ct-DNA-positive patients (12.32 months) (HR 0.74). There was a significant improvement of PFS among early ct-DNA clearers vs. non-clearers (12.32 vs. 9.92 months; HR 0.57). For those treated with 1st/ 2nd generation EGFR TKIs, this improvement in median PFS among early ct-DNA clearers vs. non-clearers was more apparent (11.76 vs. 6.8 months; HR 0.34). CONCLUSIONS: Baseline detection of the presence of ct-DNA of EGFR mutation in plasma was not predictive of first-line PFS, but is associated with extra thoracic disease. Patients with EGFR mutation and persistence of ct-DNA at first follow-up have worse PFS and overall survival (OS) in comparison to those clearing the same in plasma, especially among those treated with 1st/ 2nd generation EGFR TKIs.

Pan-Asian adapted ESMO Clinical Practice Guidelines for the diagnosis, treatment and follow-up of patients with metastatic colorectal cancer.

The European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment and follow-up of patients with metastatic colorectal cancer (mCRC), published in late 2022, were adapted in December 2022, according to previously established standard methodology, to produce the Pan-Asian adapted (PAGA) ESMO consensus guidelines for the management of Asian patients with mCRC. The adapted guidelines presented in this manuscript represent the consensus opinions reached by a panel of Asian experts in the treatment of patients with mCRC representing the oncological societies of China (CSCO), Indonesia (ISHMO), India (ISMPO), Japan (JSMO), Korea (KSMO), Malaysia (MOS), the Philippines (PSMO), Singapore (SSO), Taiwan (TOS) and Thailand (TSCO), co-ordinated by ESMO and the Japanese Society of Medical Oncology (JSMO). The voting was based on scientific evidence and was independent of the current treatment practices, drug access restrictions and reimbursement decisions in the different Asian countries. The latter are discussed separately in the manuscript. The aim is to provide guidance for the optimisation and harmonisation of the management of patients with mCRC across the different countries of Asia, drawing on the evidence provided by both Western and Asian trials, whilst respecting the differences in screening practices, molecular profiling and age and stage at presentation, coupled with a disparity in the drug approvals and reimbursement strategies, between the different countries.

Pathological response and clinical outcomes in operable triple-negative breast cancer with cisplatin added to standard neoadjuvant chemotherapy.

BACKGROUND: Response to neoadjuvant chemotherapy is associated with improved outcomes for patients with triple negative breast cancer (TNBC). Patients with residual disease are at increased risk of relapse and death from breast cancer. In this retrospective study, we aimed to evaluate the efficacy and safety of cisplatin added to standard neoadjuvant chemotherapy for locally advanced TNBC. MATERIALS AND METHODS: All TNBC treated with neoadjuvant cisplatin 60mg/m2 once in 3 weeks with weekly paclitaxel for 12 weeks, following 8 weeks of dose-dense epirubicin 90mg/m2 or doxorubicin 60mg/m2 with cyclophosphamide 600mg/m2 were analyzed retrospectively. The data related to pathological complete response, adherence to planned therapy, disease-free survival and overall survival were collected. RESULTS: Eighty-three patients were included, of whom 80% had stage III disease. Pathological complete response in both breast (T0/Tis) and axilla (N0) was observed in 48.1% of patients. Miller Payne grade 5 pathological response in the breast was seen in 61% of patients. Good partial responses (Miller Payne grades 3,4) were observed in 32.5% of patients. The remaining 6.5% were poor responders. Seventy-seven patients underwent surgery. The disease-free survival at 1 and 3 years for those who had a pathological complete response was 96.7% and 77.6%, respectively, and 92.3% and 62.7% for those who did not, respectively. The predominant adverse events were hematological, with anemia being the most common one. CONCLUSION: The addition of cisplatin to neoadjuvant chemotherapy with anthracycline and taxane in TNBC was tolerable and produced a high rate of pathological complete response. Cisplatin added to standard chemotherapy in patients with locally advanced TNBC could improve clinical outcomes.

Practical recommendation for rash and diarrhea management in Indian patients treated with tyrosine kinase inhibitors for the treatment of non-small cell lung cancer.

Tyrosine kinase inhibitors (TKIs) are a pharmaceutical class of small molecules, orally available with manageable safety profile, approved worldwide for the treatment of several neoplasms, including lung, breast, kidney and pancreatic cancer as well as gastro-intestinal stromal tumours and chronic myeloid leukaemia. In recent years, management of lung cancer has been moving towards molecular-guided treatment, and the best example of this new approach is the use of the tyrosine kinase inhibitors (TKIs) in patients with mutations in the epidermal growth factor receptor (EGFR). The identification of molecular predictors of response can allow the selection of patients who will be the most likely to respond to these tyrosine kinase inhibitors (TKIs). Gastrointestinal (GI) adverse events (AEs) are frequently observed in patients receiving EGFR tyrosine kinase inhibitor therapy and are most impactful on the patient's quality of life. Dermatologic side effects are also relatively common among patients treated with EGFR inhibitors. Evidence has emerged in recent years to suggest that the incidence and severity of rash, positively correlated with response to treatment.These skin disorders are generally mild or moderate in severity and can be managed by appropriate interventions or by reducing or interrupting the dose. Appropriate and timely management make it possible to continue a patient's quality of life and maintain compliance; however if these adverse events (AEs) are not managed appropriately, and become more severe, treatment cessation may be warranted compromising clinical outcome. Strategies to improve the assessment and management of TKI related skin AEs are therefore essential to ensure compliance with TKI therapy, thereby enabling patients to achieve optimal benefits. This article provides a consensus on practical recommendation for the prevention and management of diarrhoea and rash in Non-Small Cell Lung Cancer (NSCLC) patients receiving TKIs.

Clinicopathologic features of non-small cell lung cancer in India and correlation with epidermal growth factor receptor mutational status.

INTRODUCTION: We performed retrospective analysis of 106 patients with lung cancer for which formalin-fixed paraffin-embedded tissues was available. Their epidermal growth factor receptor (EGFR) mutation status and treatment outcomes are described. MATERIALS AND METHODS: All patients with confirmed non-small cell lung cancer (NSCLC) during Jan 2008 to Dec 2010 were included. EGFR sequencing was performed with ABI PRISM 310 genetic analyzer. RESULTS: Forty-two (39.6%) patients had mutation in one of the four exons characterized. Patients whose EGFR mutational status was not available at presentation before the start of treatment were started on chemotherapy, n = 46 (43.39%). If EGFR mutational analysis was available and mutations were present, the patients were started on either upfront tyrosine kinase inhibitor (TKI), n = 15 (14.15%) or if on chemotherapy arm were allowed to finish six cycles and then start with maintenance TKIs, n = 26 (24.52%). The median progression free survival for patients with and without mutations was 11 months (95% CI,7-14) and 9 months (95% CI,7-10) respectively. A median PFS of 14 months (95%CI, 12-16) was seen in the mutation-positive group that received both chemotherapy followed by switch maintenance with TKIs versus 8 months (95%CI, 7-8 months) in the group that received only TKI. CONCLUSION: The prevalence of EGFR mutations in this population of NSCLC patients was 39.6% with exon 19 mutation being the most common. The observed benefit of addition of chemotherapy over TKI in EGFR mutation-positive group raises the question, can we offer the therapy of chemotherapy-TKI combination to EGFR mutation-positive lung cancer patients as shown in the present study.

Management of primary and metastatic triple negative breast cancer: perceptions of oncologists from India.

BACKGROUND: In order to document the understanding of current evidence for the management of triple negative breast cancer and application of this knowledge in daily practice, we conducted an interactive survey of practicing Indian oncologists. MATERIALS AND METHODS: A core group of academic oncologists devised two hypothetical triple negative cases (metastatic and early breast cancer, respectively) and multiple choice options under different clinical circumstances. The respondents were practicing oncologists in different Indian cities who participated in either an online survey or a meeting. The participants electronically chose their preferred option based on their everyday practice. RESULTS: A total of 152 oncologists participated. Just over half (53.8%) preferred taxane based chemotherapy as first-line chemotherapy in the metastatic setting. In the adjuvant setting, a taxane regimen was chosen by 61%. Over half of respondents (52.6%) underestimated the baseline survival of a patient with node positive triple-negative tumor and 18.9% overestimated this survival compared to the estimate of the Adjuvant! program. DISCUSSION: This data offers insight into the perceptions and practice of a diverse cross-section of practicing oncologists in India with respect to their therapeutic choices in metastatic and adjuvant settings in triple negative breast cancer.

Gastrointestinal stromal tumours: a clinico-radiologic review from a single centre in South India.

Gastrointestinal stromal tumours (GISTs) are rare tumours but are the commonest mesenchymal neoplasms in the gastrointestinal tract. To our knowledge, there is no large case series in Asian countries in which a clinico-radiological descriptive analysis of these tumours has been carried out. In this retrospective study, we analysed our experience of 70 patients with histopathologically proven GISTs, who were presurgically investigated by using CT, and describe the demography, anatomical distribution, imaging features and clinical course of the GIST. We found an unusually large predominance of males in our study, stomach and small bowel appeared to have been involved similarly and small bowel tumours had a higher rate of metastases. We also highlight some unusual CT features of these tumours that we encountered during the study, such as the presence of metastatic lymphadenopathy and satellite nodules, relapse in appendices epiploicae of the bowel, metachronous liposarcoma, adrenal and lung metastases, multiplicity of lesions and aneurysmal dilatation of the bowel. Two of our patients also had multiple neurofibromas, whose association with GIST has been seen in earlier reports. To the best of our knowledge, this article presents one of the largest series of articles on GISTs, to date, in Asian countries. We conclude with a differential diagnosis of GIST, with salient features distinguishing each entity.

Primary mediastinal synovial sarcoma with transdiaphragmatic extension presenting as a pericardial effusion.

Synovial sarcoma is a distinctive soft tissue neoplasm, most commonly seen in the extremities of young adults. Mediastinal synovial sarcoma is a well-documented entity; however, in many cases, the differentiation between this and other spindle cell tumours may be difficult, especially in monophasic tumours. Unlike most pleuropulmonary synovial sarcomas which are well circumscribed, mediastinal tumours are often infiltrative and resection may not be adequate, leading to a high rate of recurrence. We present a 49-year-old man with a primary pericardial synovial sarcoma, with transdiaphragmatic intra-abdominal extension, which clinically, radiologically and grossly mimicked a tuberculous pericarditis.

A phase II study of sequential neoadjuvant gemcitabine plus doxorubicin followed by gemcitabine plus cisplatin in patients with operable breast cancer: prediction of response using molecular profiling.

This study examined the pathological complete response (pCR) rate and safety of sequential gemcitabine-based combinations in breast cancer. We also examined gene expression profiles from tumour biopsies to identify biomarkers predictive of response. Indian women with large or locally advanced breast cancer received 4 cycles of gemcitabine 1200 mg m(-2) plus doxorubicin 60 mg m(-2) (Gem+Dox), then 4 cycles of gemcitabine 1000 mg m(-2) plus cisplatin 70 mg m(-2) (Gem+Cis), and surgery. Three alternate dosing sequences were used during cycle 1 to examine dynamic changes in molecular profiles. Of 65 women treated, 13 (24.5% of 53 patients with surgery) had a pCR and 22 (33.8%) had a complete clinical response. Patients administered Gem d1, 8 and Dox d2 in cycle 1 (20 of 65) reported more toxicities, with G3/4 neutropenic infection/febrile neutropenia (7 of 20) as the most common cycle-1 event. Four drug-related deaths occurred. In 46 of 65 patients, 10-fold cross validated supervised analyses identified gene expression patterns that predicted with >or=73% accuracy (1) clinical complete response after eight cycles, (2) overall clinical complete response, and (3) pCR. This regimen shows strong activity. Patients receiving Gem d1, 8 and Dox d2 experienced unacceptable toxicity, whereas patients on other sequences had manageable safety profiles. Gene expression patterns may predict benefit from gemcitabine-containing neoadjuvant therapy.

Serum & muscle magnesium in Indians with cirrhosis of liver.

Magnesium status of Indian patients with cirrhosis of liver (alcoholic and non alcoholic) and the role of low magnesium in neuromuscular and neuropsychiatric manifestations of chronic liver disease were evaluated in 76 male cirrhotics (alcoholic 37, aged 48 +/- 11 yr, non alcoholic 39, aged 47 +/- 12 yr) and 37 male controls (aged 49 +/- 11 yr). Serum magnesium levels were similar in the 3 groups studied. Muscle magnesium in both groups of cirrhotics were significantly lower than in controls (alcoholic cirrhosis 33.77 +/- 16.85; non alcoholic cirrhosis 37.93 +/- 18.86 and controls 70.52 +/- 6.49 mEq/kg fat free dry mass; P < 0.001). Multiple regression analysis comparing muscle magnesium with clinical and biochemical parameters in cirrhosis showed that hepatic encephalopathy was associated significantly and independently with low muscle magnesium (Beta = -0.313; P = 0.01). These results indicate that patients with cirrhosis have significantly lower muscle magnesium than controls and suggests that low muscle magnesium may be a factor associated with or precipitating hepatic encephalopathy.