Induction chemotherapy in locally advanced T4b oral cavity squamous cell cancers: A regional cancer center experience.

OBJECTIVES: The present study aimed to investigate the efficacy, toxicity, and impact of induction chemotherapy (IC) in locally advanced T4b oral cavity squamous cell cancers (OSCCs). MATERIALS AND METHODS: Patients diagnosed with locally advanced T4b OSCC from January 2013 to October 2016 at our center, who received 2-3 cycles of IC and then assessed for resectability, were reviewed retrospectively. Patients' profile, response, and toxicity of IC, resectability status, and overall survival (OS) were evaluated. Statistical analyses were performed by SPSS software version 17. RESULTS: A total of 116 patients received IC, and out of them 90 (77.6%) were males. Median age at diagnosis was 43 years (range 31-62 years). Nearly 103 (88.8%) of our patients received doublet chemotherapy and the rest of the patients received triplet regimen. Majority of the patients had buccal mucosa cancers (71.6%), followed by gingivobuccal complex (21.6%) and oral tongue (6.9%) primaries. After IC, partial response was achieved in 20 (17.3%) patients, stable disease in 68 (58.6%) patients, and disease progression was noted in 28 (24.1%) patients. Post-IC, resectability was achieved in 22 (19%) of 116 patients, but 6 of them did not undergo surgery due to logistic and personal reasons. The median OS of patients who underwent surgery followed by adjuvant local therapy (n = 16) was 19.7 months (95% confidence interval [CI]: 16.0-22.8 months) and for those treated with nonsurgical local therapy (n = 100) was 7.1 months (95% CI: 5.8-8.2 months) (log-rank P = 0.000). CONCLUSIONS: IC had a manageable toxicity profile and achieved resectability in 19% of our patients with T4b OSCC. Patients underwent resection had a significantly better median OS than those who received nonsurgical local treatment.

Efficacy and safety of first-line systemic chemotherapy with epirubicin, cisplatin plus 5-fluorouracil and docetaxel, cisplatin plus 5-fluorouracil regimens in locally advanced inoperable or metastatic gastric or gastroesophageal junction adenocarcinoma: A prospective phase II study from South India.

BACKGROUND: Patients with locally advanced inoperable or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma have a poor prognosis. The maximum benefit of systemic chemotherapy is usually achieved in the first-line setting. Even though systemic chemotherapy has been used for long time, in view of unsatisfactory results, no standard regimen has been emerged. Unfortunately, till date, there is no published prospective data from India, comparing the two most commonly used triplet regimens, epirubicin, cisplatin plus 5-fluorouracil (ECF) and docetaxel, cisplatin plus 5-fluorouracil (DCF), in this patient population. MATERIALS AND METHODS: The present study aimed to compare the efficacy and safety of the first-line systemic chemotherapy with ECF and DCF regimens in locally advanced inoperable or metastatic gastric or GEJ adenocarcinoma. The primary endpoint was overall survival (OS). The secondary endpoints were overall response rate, progression-free survival (PFS), and toxicity profile. RESULTS: Between January 2015 and December 2016, 58 patients were assigned and treated with ECF (n = 30) or DCF (n = 28) regimens. The median OS was 9.4 months with ECF and 12.5 months with DCF regimen (log-rank, P = 0.000), while median PFS was 5.8 and 7.5 months, respectively (log-rank, P = 0.002). Patients in the DCF arm had more frequent reductions in chemotherapy doses than those of the ECF arm (28.6% vs. 16.7%; P = 0.54). As compared with the ECF, the DCF regimen was associated with more frequent Grades 3-4 toxicities-neutropenia (16.7% vs. 39.3%, P = 0.17), febrile neutropenia (13.3% vs. 25%, P = 0.52), mucositis (6.7% vs. 17.8%, P = 0.43), and diarrhea (6.7% vs. 14.3%, P = 0.67). CONCLUSIONS: In comparison to ECF, the DCF regimen was associated with a statistically significant 3.1 months longer median OS without any significant increase in Grades 3-4 toxicities. DCF can be considered as one of the reference regimens, in properly selected patients with advanced/metastatic gastric or GEJ adenocarcinoma.

Dual mutations and complex mutations in metastatic nonsmall cell lung cancer: A single-institution experience from South India.

Wide use and incorporation of newer diagnostic tools in the management of metastatic nonsmall cell lung cancer (NSCLC) has helped in achieving the goal of personalized treatment of this disease. With the wide use of polymerase chain reaction and fluorescence in situ hybridization increasing number of patients are being diagnosed with dual and complex mutations posing a new challenge in the management of patient with metastatic NSCLC. In this article, we would like to bring forth six such cases and the varied responses to the current available treatment in patients with complex and dual mutations. The appropriate management in these groups of patients is yet to be standardized.

Current status of systemic therapy for recurrent and/or metastatic squamous cell carcinoma of the head and neck.

Head and neck squamous cell carcinoma (HNSCC) is now the seventh most common cancer worldwide. The median overall survival for patients with recurrent and/or metastatic (R/M) HNSCC remains <1 year despite modern systemic chemotherapy and targeted agents. Palliative systemic therapy for patients with R/M HNSCC typically includes a platinum-based doublet, with an understanding that the increase in efficacy compared with single agents is primarily related to improved response rate, and not survival. Till date, the only systemic therapy regimen to demonstrate survival superiority over platinum-5-fluorouracil (5-FU) doublet is platinum, FU, and cetuximab. Epidermal growth factor receptor inhibitors, including monoclonal antibodies and tyrosine kinase inhibitors, have achieved only a modest success in R/M HNSCC. Immunotherapy represents an attractive treatment option for R/M HNSCC, with encouraging preliminary data from studies involving immune checkpoint inhibitors (e.g., pembrolizumab, nivolumab) and toll-like receptor agonists (e.g., motolimod). Given the poor prognosis of R/M HNSCC, enrollment of patients into clinical trials to investigate novel systemic agents, is necessary for further improvement of oncologic outcomes in this patient population.

A prospective study to assess the efficacy and toxicity of 5-flurouracil and cisplatin versus taxane and cisplatin as induction chemotherapy in locally advanced head and neck squamous cell cancer in a regional cancer center in India.

AIM: The aim of this study is to assess the efficacy and toxicity of 5-flurouracil (5-FU) and cisplatin (PF) versus taxane and cisplatin (TP) as induction chemotherapy in locally advanced head and neck squamous cell cancer. MATERIALS AND METHODS: There were 50 patients in each arm, matched for age, performance state, site and stage of disease. PF arm (cisplatin - 100 mg/m2 D1, 5-FU - 1000 mg/m2 D1-D5) TP arm (docetaxel - 75 mg/m2 or paclitaxel - 175 mg/m2 on D1, cisplatin 75 mg/m2 on D2), received once in 3 weeks for 3 cycles. Patients without progressive disease underwent either surgery or chemoradiation. The primary end point was overall response rate (ORR) and secondary endpoint was toxicity. RESULTS: In a total of 100 patients in our study, 44 in PF and 47 in TP arm were evaluable. ORR was 86.6% in PF arm and 82.9% in TP arm (P = 0.71).There were more Grade 3 or 4 events of neutropenia, mucositis (P ≤ 0.05) and myelosuppression diarrhea, febrile neutropenia (P ≥ 0.05) in PF arm compared with TP arm. Post-chemotherapy hospital admissions due to toxicity were more frequent in PF arm (38.6% vs. 19%), dropout rate due to toxicity (9% vs. 0%) and deaths (6.8% vs. 2.1%) were more common in PF arm compared with TP arm. CONCLUSION: TP induction chemotherapy better tolerated than PF, which has similar efficacy, further multicenter randomized controlled studies; involving a large sample size is needed to confirm our data.

A study of triple negative breast cancer at a tertiary cancer care center in southern India.

BACKGROUND: Triple negative breast cancers (TNBCs) are a diverse and heterogeneous group of tumors that by definition lack estrogen and progesterone receptors and amplification of the HER-2 gene. The majority of the tumors classified as TNBCs are highly malignant, patients are usually young and only a subgroup of patients responds to conventional chemotherapy with a favorable prognosis. Various studies have been reported in western literature on TNBCs, all highlighting the poor prognosis of this subtype. However, extensive data from India is lacking. AIM: The aim of this study was to analyze the epidemiological and clinical profile of TNBCs at our institute. MATERIALS AND METHODS: This was the retrospective study carried out in Tertiary Cancer Care Center in South India. Case files of all breast cancer patients were reviewed from the hospital database registered in 1 year and TNBC patients were selected for the study. Patient's characteristic, treatment, and histological features were analyzed. RESULTS: A total of 322 patients were registered during the period of 1 year and 26% (84/322) of total patients were TNBC. Median age of presentation was 44.5 years. About 94% (79/84) of patients had first full-term delivery before the age of 30 years. The most common presenting symptom was left sided breast lump. Locally advanced and early breast cancer (EBC) was 51% (43/84) and 42% (36/84), respectively. Metastatic breast cancer was seen in five patients. The highest numbers of patients were node negative disease (36.9%) [31/84], followed by N1 30.95% (26/84). Most of the patients had high-grade tumor. 94% (34/36) of cases of EBC had undergone upfront modified radical mastectomy. Invasive ductal carcinoma was the predominant histology except one who had medullary carcinoma. Twenty-four patients received neoadjuvant chemotherapy (NACT). There was no pathological complete remission, but all patients responded to NACT. Metastatic disease was seen in five patients. All patients had bone metastasis. CONCLUSIONS: TNBCs are highly aggressive subtype, with high grade with limited treatment options and very poor prognosis. Incidence is more in our country than the western literature. Even in our country also the incidence is varies in different region. TNBCs are significantly associated with young aged patients. There was a lack of association between tumor size and lymph node positivity.

Clinical and microbiological profile of febrile neutropenia in solid tumors and hematological malignancies at a tertiary cancer care center in South India.

BACKGROUND: Febrile neutropenia (FN) is a common but serious complication of chemotherapy in patients with solid tumors (ST) and hematological malignancies (HM). The epidemiology of FN keeps changing. OBJECTIVE: The objective was to study the epidemiology of FN in adult patients with ST and HM at Kidwai Memorial Institute of Oncology, Bangalore - A tertiary cancer care center. MATERIALS AND METHODS: Data of all episodes of FN that occurred during the period July 2011 to December 2011 were collected prospectively and analyzed. RESULTS: A total of 75 episodes of FN was observed during study period involving 55 patients. Febrile neutropenic episodes were more frequent in HM than in ST (57% vs. 43%). The rate of bloodstream infection was 14.7%. Gram-negative organisms were the predominant isolates (56.25%). Overall mortality rate was 13.3%. Presence of medical co-morbidity and positive culture predicted high mortality. Mortality rate did not differ significantly between HM and ST (14% vs. 12.5%; P = 1.0). Gram-positive bacteremia was associated with greater mortality than Gram-negative bacteremia (P = 0.02). CONCLUSION: Empiric antibiotic treatment for FN should be tailored to the locally prevalent pathogens and their susceptibility patterns.

Genetic and structural analysis of the Bacteroides conjugative transposon CTn341.

The genetic structure and functional organization of a Bacteroides conjugative transposon (CTn), CTn341, were determined. CTn341 was originally isolated from a tetracycline-resistant clinical isolate of Bacteroides vulgatus. The element was 51,993 bp long, which included a 5-bp coupling sequence that linked the transposon ends in the circular form. There were 46 genes, and the corresponding gene products fell into three major functional groups: DNA metabolism, regulation and antibiotic resistance, and conjugation. The G + C content and codon usage observed in the functional groups suggested that the groups belong to different genetic lineages, indicating that CTn341 is a composite, modular element. Mutational analysis of genes representing the different functional groups provided evidence for the gene assignments and showed that the basic conjugation and excision genes are conserved among Bacteroides spp. A group IIA1 intron, designated B.f.I1, was found to be inserted into the bmhA methylase gene. Reverse transcriptase PCR analysis of CTn341 RNA showed that B.fr.I1 was functional and was spliced out of the bmhA gene. Six related CTn-like elements were found in the genome sequences of Bacteroides fragilis NCTC9343 and Bacteroides thetaiotaomicron VPI5482. The putative elements were similar to CTn341 primarily in the tra and mob regions and in the exc gene, and several appeared to contain intron elements. Our data provide the first reported sequence for a complete Bacteroides CTn, and they should be of considerable benefit to further functional and genetic analyses of antibiotic resistance elements and genome evolution in Bacteroides.

[Fluoroscopy based surgical navitation vs. mechanical guidance system for percutaneous interventions. A controlled prospective study exemplified by distal locking of intramedullary nails]. / Fluoroskopiebasierte chirurgische Navigation vs. mechanisches Zielsystem für perkutane Eingriffe. Eine kontrollierte prospektive Studie am Beispiel der distalen Verriegelung von Marknägeln.

The aim of this study was to directly compare mechanically based targetting and surgical navigation when applied for percutaneous osteosynthesis. The distal locking procedure of intramedullary nails was used as the clinical model for a controlled prospective study. A total of 50 patients were included in two groups. In group 1, the distal locking was done with a mechanical aiming device while in group 2 this was done using a fluoroscopy based surgical navigation system. The target parameters were the precision attained, the necessary operation and fluoroscopy times as well as the number and severity of intra-operative problems. The drill-bit failed to pass through the interlocking hole in one patient with mechanical guidance and in two patients with surgical navigation. The average procedure time for distal locking with mechanical guidance was 6.9 minutes compared with 37.6 minutes with surgical navigation. An additional 44 minutes were required before skin incision and after skin closure as setup time for the navigation system. There was no significant difference in the fluoroscopy time or in the number of intra-operative technical problems. Surgical navigation increased the demand for resources but failed to improve the precision of distal locking compared with mechanical guidance. Further clinical studies are required to determine to what degree these results, using a special model, relate to other applications.