A unique RET EXON 11 (G691S) polymorphism in an Indian patient with a collision tumor of the thyroid

BACKGROUND: Collision tumors of the thyroid are rare, with occasional reports dealing with their genetic analysis. CASE PRESENTATION: A 59 year old lady presented with a neck mass, associated with hoarseness of voice of 5 years duration. Radiological examination revealed nodular masses in the left lobe of her thyroid, along with one in the isthmus, extending into the right lobe and associated with enlarged neck nodes. FNAC from the left thyroid showed features of medullary carcinoma. On total thyroidectomy, 2 distinct tumor nodules were identified in the left lobe with another in the isthmus, showing features of medullary carcinoma (MTC), papillary carcinoma and follicular variant of papillary carcinoma, respectively, accompanied with nodal metastasis. Subsequently, she underwent radioablation. RET gene analysis of the patient, her 2 daughters and a grandson revealed a unique G691S polymorphism on Exon 11. CONCLUSION: This unique case of a collision tumor of thyroid, including component of an MTC deals with the value of RET gene analysis and therapeutic implications in the index case and in family members

RMAC study:A randomized study for evaluation of metronomic adjuvant chemotherapy in recurrent head and neck cancers post salvage surgical resection in those who are ineligible for re-irradiation

Background: Adjuvant re-chemoradiation after salvage surgery improves disease-free survival in recurrent head and neck cancer. However, most patients are ineligible for re-irradiation and are kept on observation. We investigated the efficacy of metronomic adjuvant chemotherapy (MAC) in this group of patients compared to observation. Methods: This was a randomized integrated phase II/III clinical trial. Adults with recurrent head and neck cancer, who had undergone salvage surgery, but were ineligible for adjuvant re-irradiation were randomized in a 1:1 ratio to either MAC arm or observation. MAC consisted of weekly oral methotrexate (at a dose of 15 mg per square meter of body surface area) and celecoxib (at a dose of 200 mg orally twice daily) for 6 months. The primary endpoint of phase 2 was disease-free survival (DFS) while that of phase 3 was overall survival (OS). For phase 2, to detect an improvement in the hazard ratio (HR) 0.67 with MAC, with a type 1 error of 10% (1-sided), type 2 error of 30%, 105 patients were required. While for phase 3, with a target HR of 0.77, with a type 1 error of 5%, type 2 error of 20%, 318 patients were required. Here we report the results of phase 2 part of the study. Results: At a median follow up of 30.2 months (95% confidence interval (CI), 25.3 to 35.1) the 1 year and 2-year DFS were 57.4% (95% CI, 42.8–69.5) and 37.6% (95% CI, 24.1–51) in MAC arm whereas the corresponding numbers were 62.3% (95% CI, 47.8 to 73.8) and 54.2%(95% CI, 39.8 to 66.5) in observation arm, respectively (hazard ratio for progression, 1.45; 95% CI, 0.87 to 2.47; P = 0.15). In the MAC arm, the 1 and 2 year OS was 78.7% (95% CI, 64.9 to 87.6) and 48% (95% CI, 34.1 to 62).The corresponding figures in the observation arm were 79.2% (95% CI, 65.7 to 87.9) and 65.5% (95% CI, 50.9 to 76.7) (hazard ratio for death, 1.7, 95% CI, 0.94 to 3.08; P = 0.08). Conclusion: The adjuvant 6-month metronomic schedule was ineffective in improving outcomes in recurrent head and neck cancers post salvage surgery who are ineligible for re-radiation. Trial registration. Clinical trial registry of India (CTRI)- CTRI/2016/04/006872 [Registered on 26/4/2016] © 2022 Elsevier Lt

RMAC study:A randomized study for evaluation of metronomic adjuvant chemotherapy in recurrent head and neck cancers post salvage surgical resection in those who are ineligible for re-irradiation

Background: Adjuvant re-chemoradiation after salvage surgery improves disease-free survival in recurrent head and neck cancer. However, most patients are ineligible for re-irradiation and are kept on observation. We investigated the efficacy of metronomic adjuvant chemotherapy (MAC) in this group of patients compared to observation. Methods: This was a randomized integrated phase II/III clinical trial. Adults with recurrent head and neck cancer, who had undergone salvage surgery, but were ineligible for adjuvant re-irradiation were randomized in a 1:1 ratio to either MAC arm or observation. MAC consisted of weekly oral methotrexate (at a dose of 15 mg per square meter of body surface area) and celecoxib (at a dose of 200 mg orally twice daily) for 6 months. The primary endpoint of phase 2 was disease-free survival (DFS) while that of phase 3 was overall survival (OS). For phase 2, to detect an improvement in the hazard ratio (HR) 0.67 with MAC, with a type 1 error of 10% (1-sided), type 2 error of 30%, 105 patients were required. While for phase 3, with a target HR of 0.77, with a type 1 error of 5%, type 2 error of 20%, 318 patients were required. Here we report the results of phase 2 part of the study. Results: At a median follow up of 30.2 months (95% confidence interval (CI), 25.3 to 35.1) the 1 year and 2-year DFS were 57.4% (95% CI, 42.8–69.5) and 37.6% (95% CI, 24.1–51) in MAC arm whereas the corresponding numbers were 62.3% (95% CI, 47.8 to 73.8) and 54.2%(95% CI, 39.8 to 66.5) in observation arm, respectively (hazard ratio for progression, 1.45; 95% CI, 0.87 to 2.47; P = 0.15). In the MAC arm, the 1 and 2 year OS was 78.7% (95% CI, 64.9 to 87.6) and 48% (95% CI, 34.1 to 62).The corresponding figures in the observation arm were 79.2% (95% CI, 65.7 to 87.9) and 65.5% (95% CI, 50.9 to 76.7) (hazard ratio for death, 1.7, 95% CI, 0.94 to 3.08; P = 0.08). Conclusion: The adjuvant 6-month metronomic schedule was ineffective in improving outcomes in recurrent head and neck cancers post salvage surgery who are ineligible for re-radiation. Trial registration. Clinical trial registry of India (CTRI)- CTRI/2016/04/006872 [Registered on 26/4/2016] © 2022 Elsevier Lt

Nimotuzumab-cisplatin-radiation versus cisplatin-radiation in HPV negative oropharyngeal cancer

BACKGROUND: Addition of nimotuzumab to weekly cisplatin and radiation improves outcomes in head and neck cancer. HPV negative oropharyngeal cancer has unsatisfactory treatment outcomes and is a candidate for escalation of treatment. We wanted to determine whether the addition of nimotuzumab to cisplatin-radiation could improve outcomes in these poor-risk tumors.METHODS: This was a subgroup analysis of a phase 3 randomized study. In this study, locally advanced head and neck cancer patients undergoing definitive chemoradiation were randomly allocated to weekly cisplatin (30 mg/m2 IV)- radiation (66–70 Gy) {CRT arm} or nimotuzumab (200 mg weekly) -weekly cisplatin (30 mg/m2)-radiation (66–70 Gy) {NCRT arm}. The data of HPV negative oropharyngeal cancer was extracted from the database of this study for the analysis. HPV testing was done with p16 immunohistochemistry (IHC) staining and reported according to the CAP criteria. The outcomes assessed were progression-free survival (PFS), disease-free survival (DFS), locoregional control, and overall survival (OS). Interaction test was performed between the study arms and HPV status prior to doing any HPV specific analysis for each of the studied outcomes. Kaplan Meier estimates for 2 year OS with 95% CI was calculated. The hazard ratio was obtained using COX regression analysis.RESULTS: We had 187 HPV negative oropharyngeal cancers, 91 in the CRT arm and 96 in NCRT arm. The interaction test was significant for PFS (p = 0.000), locoregional control (p = 0.007) and overall survival (p = 0.002) but not for DFS (p = 0.072). The 2- year PFS was 31.5% (95%CI 21.5–42) in CRT arm versus 57.2% (95%CI 45.8–67.1) in NCRT arm (HR -0.54; 95%CI 0.36–0.79, p = 0.002). The 2-year LRC was 41.4% (95%CI 29.8–52.6) in the CRT arm versus in 60.4% (95%CI 48.7–70.2) in the NCRT arm (HR -0.61; 95%CI 0.4–0.94, p = 0.024). The addition of nimotuzumab also lead to an improvement in 2-year OS from 39.0% (95%CI 28.4–49.6) to 57.6% (95%CI 46.3–67.4) (HR-0.63, 95%CI 0.43–0.92, p = 0.018).CONCLUSIONS: The addition of nimotuzumab to weekly cisplatin-radiation improves outcomes inclusive of OS in HPV negative oropharyngeal cancers.<br/

Nimotuzumab-cisplatin-radiation versus cisplatin-radiation in HPV negative oropharyngeal cancer

BACKGROUND: Addition of nimotuzumab to weekly cisplatin and radiation improves outcomes in head and neck cancer. HPV negative oropharyngeal cancer has unsatisfactory treatment outcomes and is a candidate for escalation of treatment. We wanted to determine whether the addition of nimotuzumab to cisplatin-radiation could improve outcomes in these poor-risk tumors.METHODS: This was a subgroup analysis of a phase 3 randomized study. In this study, locally advanced head and neck cancer patients undergoing definitive chemoradiation were randomly allocated to weekly cisplatin (30 mg/m2 IV)- radiation (66–70 Gy) {CRT arm} or nimotuzumab (200 mg weekly) -weekly cisplatin (30 mg/m2)-radiation (66–70 Gy) {NCRT arm}. The data of HPV negative oropharyngeal cancer was extracted from the database of this study for the analysis. HPV testing was done with p16 immunohistochemistry (IHC) staining and reported according to the CAP criteria. The outcomes assessed were progression-free survival (PFS), disease-free survival (DFS), locoregional control, and overall survival (OS). Interaction test was performed between the study arms and HPV status prior to doing any HPV specific analysis for each of the studied outcomes. Kaplan Meier estimates for 2 year OS with 95% CI was calculated. The hazard ratio was obtained using COX regression analysis.RESULTS: We had 187 HPV negative oropharyngeal cancers, 91 in the CRT arm and 96 in NCRT arm. The interaction test was significant for PFS (p = 0.000), locoregional control (p = 0.007) and overall survival (p = 0.002) but not for DFS (p = 0.072). The 2- year PFS was 31.5% (95%CI 21.5–42) in CRT arm versus 57.2% (95%CI 45.8–67.1) in NCRT arm (HR -0.54; 95%CI 0.36–0.79, p = 0.002). The 2-year LRC was 41.4% (95%CI 29.8–52.6) in the CRT arm versus in 60.4% (95%CI 48.7–70.2) in the NCRT arm (HR -0.61; 95%CI 0.4–0.94, p = 0.024). The addition of nimotuzumab also lead to an improvement in 2-year OS from 39.0% (95%CI 28.4–49.6) to 57.6% (95%CI 46.3–67.4) (HR-0.63, 95%CI 0.43–0.92, p = 0.018).CONCLUSIONS: The addition of nimotuzumab to weekly cisplatin-radiation improves outcomes inclusive of OS in HPV negative oropharyngeal cancers.<br/

Prospective subjective evaluation of swallowing function and dietary pattern in head and neck cancers treated with concomitant chemo-radiation

Aim : Prospective subjective evaluation of swallowing function and dietary pattern in locally advanced head and neck cancer patients treated with concomitant chemo-radiotherapy (CRT). Materials and Methods : Prospective evaluation of swallowing function with performance status scale for head and neck cancer patients (PSSHN) at pre-CRT, CRT completion and at subsequent follow-ups in adult with loco-regionally advanced head and neck squamous cell carcinoma (HNSCC) patients. Results : In 47 patients (40 male, seven females; mean age 53; 72% smoker 53%, oropharyngeal cancer), the mean total PSSHN score at pre-CRT was 258.5 and decreased to 225.2 and 219.2 at two and six months respectively. Understandability of speech, normalcy in diet and eating in public at pre-CRT and six months were 91.5 and 84.4; 80.4 and 63.1; 87.3 and 76.6 respectively. In univariate analysis, pre-CRT PSSHN scores were significantly lesser in patients with severe pre-CRT dysphagia (P = 0.001), hypopharyngeal cancer (P = 0.244) and advanced T-stage (T3/4) disease (P = 0.144). At CRT completion, there was significant reduction of PSSHN scores in patients with severe pre-CRT dysphagia (P = 0.008), post-CRT weight loss (&gt;10%) and disease progression (P = 0.039). At two months and six months, 17 (57%) and 11 (73.5%) patients respectively showed change in dietary habit. Mean increase in meal time was 13% and 21% at two and six-month follow-up. Conclusions : HNSCC patients show deterioration in swallowing function after CRT with normalcy of diet in maximum and eating in public least affected. Pre-CRT severity of dysphagia, weight loss&gt; 10% and disease progression have significant correlation with higher swallowing function deterioration after CRT

Fascin overexpression promotes neoplastic progression in oral squamous cell carcinoma

<p>Abstract</p> <p>Background</p> <p>Fascin is a globular actin cross-linking protein, which plays a major role in forming parallel actin bundles in cell protrusions and is found to be associated with tumor cell invasion and metastasis in various type of cancers including oral squamous cell carcinoma (OSCC). Previously, we have demonstrated that fascin regulates actin polymerization and thereby promotes cell motility in K8-depleted OSCC cells. In the present study we have investigated the role of fascin in tumor progression of OSCC.</p> <p>Methods</p> <p>To understand the role of fascin in OSCC development and/or progression, fascin was overexpressed along with vector control in OSCC derived cells AW13516. The phenotype was studied using wound healing, Boyden chamber, cell adhesion, Hanging drop, soft agar and tumorigenicity assays. Further, fascin expression was examined in human OSCC samples (N = 131) using immunohistochemistry and level of its expression was correlated with clinico-pathological parameters of the patients.</p> <p>Results</p> <p>Fascin overexpression in OSCC derived cells led to significant increase in cell migration, cell invasion and MMP-2 activity. In addition these cells demonstrated increased levels of phosphorylated AKT, ERK1/2 and JNK1/2. Our in vitro results were consistent with correlative studies of fascin expression with the clinico-pathological parameters of the OSCC patients. Fascin expression in OSCC showed statistically significant correlation with increased tumor stage (<it>P </it>= 0.041), increased lymph node metastasis (<it>P </it>= 0.001), less differentiation (<it>P </it>= 0.005), increased recurrence (<it>P </it>= 0.038) and shorter survival (<it>P </it>= 0.004) of the patients.</p> <p>Conclusion</p> <p>In conclusion, our results indicate that fascin promotes tumor progression and activates AKT and MAPK pathways in OSCC-derived cells. Further, our correlative studies of fascin expression in OSCC with clinico-pathological parameters of the patients indicate that fascin may prove to be useful in prognostication and treatment of OSCC.</p

Hypercalcemia and Treated Breast Cancers: The Diagnostic Dilemma

The relationship of hypercalcemia with cancer is well described in the literature. Breast cancer is the commonest malignancy associated with hypercalcemia; the detection of hypercalcemia in these patients usually signifies metastatic disease and is associated with a poor prognosis. However, the treating oncologist should keep in mind that a strong correlation exists between breast cancer and primary hyperparathyroidism. We present a case of a patient of treated breast cancer who, in the absence of metastatic bone disease, developed hypercalcemia due to hyperparathyroidism secondary to a parathyroid adenoma

Original Article - Squamous cell carcinoma of the maxillary sinus: A Tata Memorial Hospital experience

Background: The optimal treatment of maxillary sinus carcinoma remains to be defined and there is a paucity of Indian studies on the subject. Aims: To present experience of management of squamous cell carcinoma of the maxillary sinus treated with curative intent at a single institution. Settings and Design:Retrospective study of patients with squamous cell carcinoma of the maxillary sinus who presented between 1994 to 1999. Materials and Methods:The records of 73 patients with squamous cell carcinoma of the maxillary sinus were analyzed. Sixty-two patients were evaluable. Forty patients (65%) were treated with surgery followed by postoperative radiotherapy, five patients (8%) were treated with radiotherapy alone, five patients (8%) were treated with surgery alone; 12 patients (19%) received chemotherapy. Statistical analysis used: Statistical analysis was done using Kaplan-Meier method. Results: The majority of patients presented with locally advanced disease (52, 84%); nodal involvement was observed in five patients (8%). The most common site of recurrence was at the primary site, which was observed in 28 patients (45%) and regional failures occurred in 10 (16%). The 3 and 5-year overall survival was 38% and 35% and the disease free survival was 29% and 26% respectively. The 5-year overall survival after surgery and postoperative radiotherapy was 42%. Conclusions:The majority of patients present with advanced disease resulting in poor outcomes to conventional treatment modalities. Locoregional tumor progression remains a significant pattern of failure. New approaches such as neoadjuvant or concomitant chemoradiotherapy with aggressive surgery need to be considered and evaluated in prospective studies