Drug susceptibility testing of circulating lung cancer cells for personalized treatment.

The presence of Circulating tumor cells (CTCs) has been proven to be correlated with disease progression and the patient's response to treatment. However, the culture of CTCs for clinical utility is still a big challenge. We have developed a short-term method that enables CTCs culture and provides an opportunity to monitor drug susceptibility testing in individual patients. In a proof-of-concept study, we established a unique method using Matrigel® coated in 96 well plate to enable cancer cell clusters to attach and proliferate. The culture method using Matrigel® provides in vitro conditions and improves the attachment and differentiation of anchorage-dependent epithelial cells proliferation and mimics the tumor microenvironment. We further treated the cells attached to Matrigel® with the same drug regimen as the patient has undergone. Around 30.7% of the CTCs were viable after the drug treatment. We also correlated the decrease in cell viability after drug treatment with the reduction in the pleural effusion of the patient as seen by the images obtained from CT scans pre-and post-treatment. Moreover, as per the RECIST criterion, the patient had exhibited a positive response to the treatment. The short-term culturing of CTC along with the drug susceptibility testing offers a novel method to predict patient response to the treatment and could be utilized for screening suitable drug combinations for personalized treatment.

Primary mucinous carcinomas of the lung: Clinical characteristics and treatment outcomes.

INTRODUCTION: Invasive mucinous adenocarcinoma (IMA) of the lung is a distinct histologic variant of adenocarcinomas comprising about 2%-10% of lung adenocarcinomas. A large proportion of IMAs carry KRAS mutations and only rarely epidermal growth factor receptor (EGFR) mutations or ALK/ROS translocations; thus, most cases are not amenable for targeted therapy at present. This study was conducted to elicit the unique clinicopathological characteristics of IMA. MATERIALS AND METHODS: Medical records of patients diagnosed with IMA by needle biopsy at Kidwai Cancer Institute, Bangalore, from 2013 to 2018, were retrieved and reviewed. Statistical analysis was performed using SPSS version 23.0 (IBM Corp., Armonk, NY, USA). RESULTS: Four hundred and ninety cases of needle biopsy of the lung were diagonosed at our institute between January 2013 and December 2018. Nine cases (1.8%) were diagnosed as IMA. The median age of presentation was 59 years. Six (66.7%) were current smokers with pack-year > 20. Three (33.3%) of the cases were initially misdiagnosed as pneumonia in view of computed tomography findings. The lung was the most common site of metastasis (77.8%). Serum Carcinoembryonic Antigen (CEA) was elevated in six cases (66.7%). None of the cases had any driver mutations in EGFR gene or ALK and ROS1 translocations. All cases were treated with pemetrexed-carboplatin doublet followed by pemetrexed maintenance till progression. The median progression-free survival (PFS) was 15 months (range: 5-18 months). Docetaxel was given as the second-line chemotherapy in all progressed patients. Best response noted was stable disease, seen in 4 (57.1%) cases. The median PFS for docetaxel was 6 months (range: 3-8 months). The median overall survival was 22 months (range: 9-27 months). Patients with initially raised CEA at progression had a serial rise in serum CEA. CONCLUSIONS: IMA is rarely diagnosed on needle biopsies due to insufficient tissue. They mimic pneumonia on imaging, thus delaying diagnosis. EGFR mutations, ALK, and ROS1 translocations are usually negative making them ineligible for tyrosine kinase inhibitors. Response to chemotherapy is modest.

Follicular lymphoma transforming to DLBCL and reverting back to follicular lymphoma at relapse-a case report.

BACKGROUND: Transformation of low-grade follicular lymphoma to high-grade diffuse large B cell lymphoma (DLBCL) is known. However, the opposite is not commonly reported. In this report, we present a case of follicular lymphoma that underwent transformation to DLBCL. Three years after treatment for histologic transformation, the patient presented again with low-grade follicular lymphoma at the same site which is unusual in the natural history of follicular lymphoma. CASE PRESENTATION: A 50-year-old female patient presented to us with complaints of slowly progressing swelling in the neck on the left side for a duration of 1 year. Past history of the patient revealed a diagnosis of follicular lymphoma in 2004 for which the patient had taken prednisolone and chlorambucil. Details of staging were not available with the patient. After a complete work-up, she was diagnosed as DLBCL, stage IIIE. She was treated with 6 cycles of CHOP regimen. She had very good response to chemotherapy. However, she defaulted and was lost to follow-up. She presented again after 3 years with history of painless progressive swelling in the right side of the neck for the last 1 year. Examination revealed cervical lymph nodes and ascites. This time, a repeat biopsy and immunohistochemistry was suggestive of follicular lymphoma. In view of significant ascites, she was started on chemotherapy with CVP regimen. After 6 cycles, she has good partial response and resolution of ascites. She is currently on follow-up. CONCLUSIONS: We have presented a case of FL that has transformed to DLBCL after 10 years of diagnosis. After HT, she was treated with CHOP chemotherapy and the patient relapsed again after 3 years with follicular lymphoma histology. This case highlights the unique and varied natural history of follicular lymphoma that may be attributed to different subclones of malignant cells that may have arisen from a common progenitor FL cell and differential effect of chemotherapy on these subclones.

Coughing up - Small cell carcinoma lung with gingival metastasis.

Small cell lung cancer (SCLC) is known for its metastatic potential. The most common sites are liver, adrenal, bone and brain. We report a case of a 37year old female patient, diagnosed with SCLC, presenting with gingival metastasis, an unusual metastatic site. Radiation therapy to the metastatic lesion to a dose of 20 Gray in 5 fractions over 5days was delivered which achieved haemostasis and good palliation. However, the patient expired in 2months owing to systemic metastasis.

Orbital medulloepithelioma in an adult patient: Radiation-induced second neoplasia?

Second cancers in survivors of hereditary retinoblastoma occur much more commonly than in the general population. This can be attributed both to the germline mutation of the RB gene and chemoradiation used for treatment of this paediatric cancer. Medulloepithelioma is an uncommon tumor of neuroectodermal origin, seen largely in the paediatric population and rarely reported in adults. Though the incidence of second malignancies is common in retinoblastoma, medulloepithelioma as a second malignancy in retinoblastoma survivors is rare, with only one case reported so far. Herein, we present a case of a 29-year-old patient presenting with medulloepithelioma of the right orbit, arising in the radiation field of previously treated retinoblastoma. This case was also peculiar in that though the origin of tumor was in the eyeball it had a very aggressive clinical course.