A randomized phase 3 trial comparing nimotuzumab plus cisplatin chemoradiotherapy versus cisplatin chemoradiotherapy alone in locally advanced head and neck cancer.

BACKGROUND: Because the addition of nimotuzumab to chemoradiation in patients with locally advanced head and neck cancer improved outcomes in a phase 2 study, the authors conducted a phase 3 study to confirm these findings. METHODS: This open-label, investigator-initiated, phase 3, randomized trial was conducted from 2012 to 2018. Adult patients with locally advanced head and neck cancer who were fit for radical chemoradiation were randomized 1:1 to receive either radical radiotherapy (66-70 grays) with concurrent weekly cisplatin (30 mg/m2 ) (CRT) or the same schedule of CRT with weekly nimotuzumab (200 mg) (NCRT).The primary endpoint was progression-free survival (PFS); key secondary endpoints were disease-free survival (DFS), duration of locoregional control (LRC), and overall survival (OS). An intent-to-treat analysis also was performed. RESULTS: In total, 536 patients were allocated equally to both treatment arms. The median follow-up was 39.13 months. The addition of nimotuzumab improved PFS (hazard ratio [HR], 0.69; 95% CI, 0.53-0.89; P = .004), LRC (HR, 0.67; 95% CI, 0.50-0.89; P = .006), and DFS (HR, 0.71; 95% CI, 0.55-0.92; P = .008) and had a trend toward improved OS (HR, 0.84; 95% CI, 0.65-1.08; P = .163). Grade 3 through 5 adverse events were similar between the 2 arms, except for a higher incidence of mucositis in the NCRT arm (66.7% vs 55.8%; P = .01). CONCLUSIONS: The addition of nimotuzumab to concurrent weekly CRT improves PFS, LRC, and DFS. This combination provides a novel alternative therapeutic option to a 3-weekly schedule of 100 mg/m2 cisplatin in patients with locally advanced head and neck cancer who are treated with radical-intent CRT.

Health-related quality of life in patients with metastatic, relapsed, or inoperable squamous cell carcinoma of the head and neck in India.

OBJECTIVE: The objective of this study was to evaluate changes in health related quality of life (HRQoL) in patients with metastatic head and neck (H&N) cancer randomized to receive metronomic (methotrexate and celecoxib) or cisplatin chemotherapy. METHODS: Patients older than 18 years, with a Karnofsky Performance score of ≥70, and diagnosed with metastatic, locally advanced inoperable or recurrent head and neck (H&N) cancer not amenable to surgery or radiation were randomized (1:1) to receive metronomic or cisplatin chemotherapy. All patients were recruited from the Tata Memorial Hospital, Mumbai, India. In addition to demographic and baseline clinical characteristics, patients were asked to rate their HRQoL using the EORTC QLQ-C30 and the EORTC QLQ-H&N35 questionnaires (Indian versions) at baseline and at the end of each chemo cycle (every 3 weeks) till the end of study or early termination. RESULTS: Of the 110 patients screened, 87 agreed to participate in the study. Mean age of the study population was 47.5 years (S.D. ±10.04) for the metronomic group and 47.2 years (S.D. ±9.89) for the cisplatin group. Overall quality of life was not significantly different between the two treatment groups from baseline to end of treatment. However, there was a statistically significant improvement in Pain QLQ-C30 score from baseline to week 3 (OR = 3.14, p = 0.036) and week 6 (OR = 3.33, p = 0.034) in the metronomic arm compared with the cisplatin arm. CONCLUSION: In addition to improvements in survival, understanding the impact of treatment options on changes in HRQoL is important as it can aid physicians in making treatment and rehabilitation decisions for patients with advanced inoperable H&N cancer.

Can multiparametric MRI and FDG-PET predict outcome in diffuse brainstem glioma? A report from a prospective phase-II study.

PURPOSE: To study the impact of multiparametric MRI and (18)F-FDG-PET on the outcome of children with diffuse intrinsic pontine gliomas (DIPG). MATERIALS AND METHODS: Imaging data from a phase-II prospective therapeutic study in children with newly diagnosed DIPG were considered for evaluation. They included baseline MRI with contrast enhancement before treatment. Functional imaging included MR spectroscopy, MR perfusion and FDG-PET studies. All patients (n = 20) had baseline MRI and 11 patients had FDG-PET. Response was assessed by MRI and PET 4 weeks after therapy. Baseline imaging findings were correlated with survival. Presence or absence of adverse parameters on MRI (heterogeneous contrast enhancement, hyperperfusion or increased choline:NAA ratio) was used to develop a cumulative radiological prognostic index (RPI). Sensitivity and specificity of each imaging modality in tumour grading was estimated. RESULTS: The cumulative RPI was able to classify the patients into different grades and was predictive of overall survival (p = 0.02). MR perfusion also predicted survival (p = 0.039). Sensitivity and specificity of MRI and FDG-PET to detect low-grade gliomas were low to moderate (33-66%), but moderate to high in detecting high-grade gliomas (50-100%). Baseline FDG uptake on PET scan did not correlate with survival (p = 0.7). CONCLUSIONS: Cumulative RPI was able to classify tumours into different grades and predicted clinical outcome. At baseline, MR hyperperfusion indicated a shorter survival for DIPG patients. Sensitivity and specificity of imaging modalities to detect low-grade gliomas were poor.

Inferior vena cava leiomyosarcoma with liver metastasis at presentation in a young male: A challenging diagnostic quandary.

Leiomyosarcomas of vascular origin are very rare tumors, predominantly affecting the inferior vena cava (IVC). Although vascular leiomyosarcomas are slow-growing, their non-specific and late presentation results in delayed diagnosis which portends a very poor prognosis. Here we report a case of a 24-year-old man who presented with abdominal pain since 15 days and was found to have unresectable metastatic leiomyosarcoma of the inferior vena cava at initial diagnosis.

Radiation Therapy Dose Escalation in Unresectable Ewing Sarcoma: Final Results of a Phase 3 Randomized Controlled Trial.

PURPOSE: Our aim was to assess the effect of radiation therapy (RT) dose escalation on outcomes in surgically unresectable Ewing sarcoma (ES)/primitive neuroectodermal tumor (PNET). METHODS AND MATERIALS: Patients with nonmetastatic unresectable ES/PNET (excluding intracranial/chest wall) receiving vincristine, doxorubicin, cyclophosphamide, ifosfamide, and etoposide chemotherapy, planned for definitive RT, were accrued in this single-institution, open-label, phase 3 randomized controlled trial. Randomization was between standard dose RT (SDRT; 55.8 Gy/31 fractions/5 days a week) versus escalated dose RT (EDRT; 70.2 Gy/39 fractions/5 days a week) with a primary objective of improving local control (LC) by 17% (65%-82%). Secondary outcomes included disease-free survival (DFS), overall survival (OS), and functional outcomes by Musculoskeletal Tumor Society score. RESULTS: Between April 2005 and December 2015, 95 patients (SDRT 47 and EDRT 48) with a median age of 17 years (interquartile range, 13-23 years) were accrued. The majority of patients were male (59%). Pelvis was the most common site of primary disease (n = 60; 63%). The median largest tumor dimension (9.7 cm) and the median maximum standardized uptake value (8.2) on pretreatment fluorodeoxyglucose positron emission tomography-computed tomography were similar. At a median follow-up of 67 months, the 5-year LC, DFS, and OS for the entire cohort was 62.4%, 41.3%, and 51.9%, respectively. The 5-year LC was significantly better in EDRT compared with SDRT (76.4% vs 49.4%; P = .02). The differences in DFS and OS at 5 years (for EDRT vs SDRT) did not achieve statistical significance (DFS 46.7% vs 31.8%; P = .22 and OS 58.8% vs 45.4%; P = .08). There was a higher incidence of Radiation Therapy Oncology Group grade >2 skin toxic effects (acute) in the EDRT arm (10.4% vs 2.1%; P = .08) with excellent functional outcomes (median Musculoskeletal Tumor Society score = 29) in both arms. CONCLUSIONS: EDRT results in improved LC with good functional outcomes without a significant increase in toxic effects. Radiation dose escalation should be considered for surgically unresectable nonmetastatic ES/PNET.

Implications of limited exolaryngeal disease and cricoarytenoid joint involvement in organ conservation protocols for laryngopharyngeal cancers: Results from a prospective study.

BACKGROUND: To identify clinicoradiological factors that determine functional outcomes in laryngopharyngeal cancers treated with chemoradiotherapy. METHODS: One hundred patients of locally advanced laryngopharyngeal cancers who were treated with chemoradiotherapy were accrued in this prospective study. The coprimary endpoint of the study was local control (LC) and functional larynx preservation survival (FLPS). RESULTS: The median follow-up was 39 months. Thirty-nine patients had a local failure of which 17 underwent a salvage laryngectomy. A dysfunctional larynx with clinic-radiologically disease was seen in only 1 patient. Factors significant for LC were thyroid cartilage erosion/lysis and cricoarytenoid joint involvement. Within the T4a subset, patients with exolaryngeal disease through the soft tissue framework had significantly better LC and FLPS than those with cartilage erosion/lysis. CONCLUSIONS: Patients with limited exolaryngeal disease through the soft-tissue framework can be considered for functional organ preservation, while those with thyroid cartilage involvement and cricoarytenoid joint involvement are not suitable.

Salvage surgery in head and neck cancer: Does it improve outcomes?

BACKGROUND: Studies reporting outcomes of salvage surgery in locally advanced head and neck squamous cell carcinoma (LAHNSCC) have inherent biases like biological and temporal selection. Our study considered all patients deemed fit for salvage surgery and compared to those who underwent surgery versus those who refused it thus throwing light on the real world benefit of salvage surgery. METHODS: This was a post hoc analysis of a phase 3 randomized trial conducted between 2012 and 2018. Out of 536 LAHNSCC patients randomised in the study, 113 patients had residual disease or recurrent disease and were planned for salvage surgery in a multidisciplinary clinic. Patients were divided into 2 cohorts for comparison, willing for salvage surgery (n = 91) and unwilling for salvage surgery(n = 22). The primary endpoint was overall survival. RESULTS: The median follow up was 28.7 months (95%CI 23.9-33.5 months). Out of the 91 patients who were willing for salvage surgery, 78 underwent same. The median survival in cohort of patients willing for salvage surgery was 22.0 months (95%CI 10.1-33.9) while it was 9.7 months (95%CI 6.6-12.8) in patients who were unwilling for salvage surgery (HR = 0.262 95%CI HR 0.147-0.469, p = 0.000). CONCLUSION: Salvage surgery leads to a substantial improvement in outcomes in head and neck cancers and should be the de facto standard of care in patients who are eligible for the same.

Analysis of bone and soft-tissue sarcomas registered during the year 2012 at Tata Memorial Hospital, Mumbai, with clinical outcomes.

INTRODUCTION: Primary bone and soft tissue sarcomas are rare, but diagnostically and therapeutically challenging group of tumors, requiring multidisciplinary management. There are limited documented studies from multidisciplinary teams , in the form of comprehensive analysis of these tumors, from our country. This study is an analysis of cases of osteosarcomas, Ewing sarcomas (ESs), chondrosarcomas (CSs), and soft-tissue sarcomas (STSs), registered at our institution during 2012. METHODS: Clinical details, including outcomes of cases of bone and STSs, during the year 2012, were retrieved from the medical records of our institution and were further analyzed. RESULTS: Ninety-five high-grade, extremity-based, treatment-naïve cases of osteosarcomas were treated with a novel, dose-dense, nonhigh-dose methotrexate-based OGS-12 protocol. Good histopathologic response (necrosis ≥90%) was achieved in 59% nonmetastatic and 56% metastatic patients. At a median follow-up of 48 months, the estimated 5-year event-free survival and overall survival (OS) were 67% and 78%, respectively. In the metastatic cohort at a median follow-up of 51 months, the 5-year estimated progression-free survival was 24% and OS was 26%. Among 87 (73.2%) nonmetastatic and 32 (26.8%) metastatic, analyzable cases of ES, at a median follow-up of 40 months, the disease-free survival (DFS) and OS in the nonmetastatic group were 62% and 83%; in the metastatic group, they were 37.5% and 65.6%, respectively. Among 40 cases of CSs (33 nonmetastatic and 7 metastatic), 21 had limb salvage surgery while 5 had amputation. Microscopically, 90.4% were Grade II CSs. Five-year OS and DFS were 84.6% and 71%, respectively. Among 189 high-grade, extremity-based STSs (89% nonmetastatic), synovial sarcoma was the most common subtype (31%). Eighty-five percent had limb preservation surgery; a majority were offered adjuvant radiation with or without chemotherapy. At a median follow-up of 51 (1-63) months, 3-year local control, DFS, and OS were 81%, 48%, and 64%, respectively. CONCLUSIONS: The novel OGS 12 and Ewing Family of Tumors 2001 protocols have shown comparable outcomes to international standards in cases of osteosarcoma and ES, respectively, and merit wider applications, especially in low- and middle-income countries (LMICs). Outcomes in STS and CSs were also comparable and underscore the importance of a multidisciplinary approach for the management of sarcomas in LMICS.

Once-a-Week Versus Once-Every-3-Weeks Cisplatin Chemoradiation for Locally Advanced Head and Neck Cancer: A Phase III Randomized Noninferiority Trial.

Purpose Chemoradiation with cisplatin 100 mg/m2 given once every 3 weeks is the standard of care in locally advanced head and neck squamous cell cancer (LAHNSCC). Increasingly, low-dose once-a-week cisplatin is substituted because of perceived lower toxicity and convenience. However, there is no level 1 evidence of comparable efficacy to cisplatin once every 3 weeks. Patients and Methods In this phase III randomized trial, we assessed the noninferiority of cisplatin 30 mg/m2 given once a week compared with cisplatin 100 mg/m2 given once every 3 weeks, both administered concurrently with curative intent radiotherapy in patients with LAHNSCC. The primary end point was locoregional control (LRC); secondary end points included toxicity, compliance, response, progression-free survival, and overall survival. Results Between 2013 and 2017, we randomly assigned 300 patients, 150 to each arm. Two hundred seventy-nine patients (93%) received chemoradiotherapy in the adjuvant setting. At a median follow-up of 22 months, the estimated cumulative 2-year LRC rate was 58.5% in the once-a-week arm and 73.1% in the once-every-3-weeks arm, leading to an absolute difference of 14.6% (95% CI, 5.7% to 23.5%); P = .014; hazard ratio (HR), 1.76 (95% CI, 1.11 to 2.79). Acute toxicities of grade 3 or higher occurred in 71.6% of patients in the once-a-week arm and in 84.6% of patients in the once-every-3-weeks arm ( P = .006). Estimated median progression-free survival in the once-a-week arm was 17.7 months (95% CI, 0.42 to 35.05 months) and in the once-every-3-weeks arm, 28.6 months (95% CI, 15.90 to 41.30 months); HR, 1.24 (95% CI, 0.89 to 1.73); P = .21. Estimated median overall survival in the once-a-week arm was 39.5 months and was not reached in the once-every-3-weeks arm (HR, 1.14 [95% CI, 0.79 to 1.65]; P = .48). Conclusion Once-every-3-weeks cisplatin at 100 mg/m2 resulted in superior LRC, albeit with more toxicity, than did once-a-week cisplatin at 30 mg/m2, and should remain the preferred chemoradiotherapy regimen for LAHNSCC in the adjuvant setting.

Clinicopathological Features of a Series of 27 Cases of Post-Denosumab Treated Giant Cell Tumors of Bones: A Single Institutional Experience at a Tertiary Cancer Referral Centre, India.

Giant cell tumor of bone (GCTB) is mostly a benign tumor, but associated with recurrences and metastasis. Lately, denosumab is being utilized in the treatment of certain GCTBs. Twenty-seven tumors, analyzed in the present study, occurred in 16 males and 11 females (M: F = 1.45:1), in the age-range of 16 to 47 years (mean = 29.5, median = 29). Most tumors were identified in the tibia(6) and femur(6), followed by the humerus(3), radius(3), pelvis(3), fibula(3), sacrum(1), metacarpal(1) and metatarsal(1) bones. There were 18(66.6 %) primary and 9(33.3 %) recurrent tumors. Exact tumor size (19 cases) varied from 3.7 to 15 cm (mean = 7.8, median = 6.4). Eight of the 19 tumors (42.1 %) had size more than or equal to 8 cm. On histopathologic examination of post-denosumab treated specimens, more than half cases (15)(55.5 %) revealed complete absence of osteoclast-like giant cells (OCLGs) and 12 cases revealed residual OCLGCs. In addition, there was replacement by fibro-osseous tissue, including reactive woven bone or osteoid in most cases, followed by variable amount of spindle cells, hyalinisation, fibrosis and chronic inflammatory cells, including lymphocytes, macrophages and plasma cells. Post-treatment follow-up (25 cases, 92.5 %), over 7-27 months duration (median = 18), revealed 20 cases continuously disease-free. Five patients developed recurrences at 9, 12, 13, 14 and 18 months, respectively. Out of these, who underwent repeat surgical intervention, 4 patients are alive with no evidence of disease and a single patient, planned for a second surgery, is alive-with-disease. Denosumab was mostly offered to patients with large sized, borderline salvageable tumors, in order to decrease the morbidity of index surgical procedure, that led to disappearance of OCLGCs in most cases. Post-denosumab treated GCT cases appear as low grade osteosarcomas on histopathologic examination, but lack the clinical behaviour of an osteosarcoma, therefore may be considered as pseudo malignant bony lesions.

Role of neoadjuvant chemotherapy in advanced carcinoma of the hypopharynx and larynx.

BACKGROUND: To assess the response rate and impact of neoadjuvant chemotherapy (NACT) in advanced carcinoma of the hypopharynx and larynx. MATERIALS AND METHODS: This is a retrospective case series of 80 patients with locally advanced laryngopharynx carcinoma who received NACT from April 2010 to October 2011 at our tertiary care center. The patients received NACT either for achieving resectability or for organ preservation. RESULTS: Majority of the patients (60%) had T4 a disease. Grade 3 and 4 neutropenia was seen in 18%, febrile neutropenia in 4%, mucositis in 4%, diarrhea in 5%, and vomiting in 3% patients. Resectability could be achieved in 34%, and larynx was preserved in 51% patients at a mean follow-up of 13 months. CONCLUSIONS: NACT was safe with acceptable toxicity. Majority of the patients who achieved resectability had oropharyngeal involvement. NACT followed by concurrent chemoradiotherapy could provide a high rate of organ preservation.

A tertiary care experience with paclitaxel and cetuximab as palliative chemotherapy in platinum sensitive and nonsensitive in head and neck cancers.

BACKGROUND: The combination of paclitaxel and cetuximab (PaCe) has led to an encouraging response rate in Phase 2 setting with limited toxicity. The aim of our study was to assess the efficacy of this regimen in our setting in platinum sensitive and nonsensitive patients. METHODS: This was a retrospective analysis of head and neck cancer patients treated with weekly PaCe as palliative chemotherapy between May 2010 and August 2014. The standard schedule of cetuximab along with 80 mg/m2 of weekly paclitaxel was administered till either disease progression or withdrawal of patient's consent. The toxicity and response were noted in accordance with CTCAE version 4.02 and RECIST version 1.1 criteria, respectively. The response rates between platinum sensitive and nonsensitive patients were compared by Chi-square test. Overall survival (OS) and progression-free survival (PFS) were estimated by Kaplan-Meier survival method and log-rank test was used for comparison. Cox proportional hazard model was used for identification of factors affecting PFS and OS. RESULTS: One Hundred patients with a median age of 52 years (interquartile range: 46-56 years) were included. Forty-five patients (45%) were platinum insensitive, whereas 55 patients (55%) were platinum sensitive. In platinum insensitive patients and sensitive patients, the response rates were 38.5% and 22.2%, respectively (P = 0.104), whereas the symptomatic benefit in pain was seen in 89.5% and 71.7%, respectively (P = 0.044). The median PFS in platinum insensitive and sensitive patients were 150 and 152 days, respectively (P = 0.932), whereas the median OS was 256 days (95% confidence interval [95% CI]: 168.2-343.8 days) and 314 days (95% CI: 227.6-400.4 days), respectively (P = 0.23). Nineteen patients (19%) had grades 3-4 adverse events during chemotherapy. CONCLUSION: Weekly paclitaxel combined with cetuximab has promising efficacy and good tolerability in the palliative setting in advanced head and neck cancer in both platinum sensitive and insensitive patients.

Neoadjuvant chemotherapy in geriatric head and neck cancers.

BACKGROUND: The purpose of this study was to present our findings on the treatment completion rates and outcomes in geriatric patients with head and neck cancer treated with neoadjuvant chemotherapy followed by definitive therapy. METHODS: Geriatric patients with locally advanced head and neck cancer who received neoadjuvant chemotherapy were selected for this analysis. Overall survival (OS) and progression-free survival (PFS) were estimated. RESULTS: Forty-six of 49 patients completed neoadjuvant chemotherapy (93.9%). The compliance to local treatment was 73.3% and the median OS was 49.9 months (95% confidence interval [CI] = 22.0-77.8 months) in patients who received neoadjuvant chemotherapy for organ preservation (n = 15). In patients receiving neoadjuvant chemotherapy for technically unresectable disease, the corresponding figures were 82.06% and 9.0 months (95% CI = 5.9-12.1 months), respectively. CONCLUSION: Individualized neoadjuvant chemotherapy protocols in geriatric patients have high compliance rates to treatment and the median OS in geriatric patients treated for organ preservation is similar to that of young patients. © 2017 Wiley Periodicals, Inc. Head Neck 39: 886-892, 2017.

Results of a phase II randomized controlled clinical trial comparing efficacy of Cabazitaxel versus Docetaxel as second line or above therapy in recurrent head and neck cancer.

BACKGROUND: Cabazitaxel has shown activity in squamous cancer cell lines and in taxane resistant cell lines. Hence we planned a phase 2 study to evaluate the efficacy of cabazitaxel against Docetaxel in recurrent head and neck cancer, post first line treatment. METHODS: This was a phase 2, investigator initiated, randomized controlled trial of Docetaxel (75 mg/m2) versus Cabazitaxel (20 mg/m2), in patients with head and neck cancer with ECOG performance status 0-2 who have been exposed to at least one line of chemotherapy, involving a sample size of 92 (46 per group)(CTRI/2015/06/005848). Disease control rate at 6 weeks was assessed and compared using the chi-square test. RESULTS: The disease control rate at 6 weeks was better in the Docetaxel arm over the cabazitaxel arm (52.3% versus 13.6%, p = 0.017). The median progression free survival was 21 days (95% CI 5.28 to 36.72 days) in the cabazitaxel arm versus 61 days (95% CI 21.39 to 100.60 days) in the Docetaxel arm (HR-1.455, 95% CI 0.919-2.304, p = 0.100). The median overall survival was 115 days (95% CI 74.04 to 155.95 days) in the cabazitaxel arm versus 155 days (95% CI 148.6 to 161.40 days) in the Docetaxel arm (HR-1.464, 95% CI 0.849-2.523, p = 0.170). CONCLUSION: Docetaxel had a superior disease control rate at 6 weeks compared to cabazitaxel.

Disseminated cysticercosis: role of whole body Magnetic Resonance Imaging.

UNLABELLED: Cysticercercosis is a parasitic infection that is commonly seen in developing countries. Treatment of cysticercosis can precipitate an intense inflammatory response which may further worsen the symptoms. Whole body MRI is an upcoming tool for screening of diseases. It can be acquired in the same setting as a brain MRI in reasonable time without any additional hardware. We present a case wherein whole body MRI was used to evaluate disseminated cysticercosis. It can prove as useful screening tool to gauge the disease load and modify the treatment plan accordingly, especially in endemic areas. KEY WORDS: disseminated cysticercosis, whole body MRI.

Solitary osseous metastasis of rectal carcinoma masquerading as osteogenic sarcoma on post-chemotherapy imaging: a case report.

Solitary metastases from colorectal carcinoma in the absence of hepatic or pulmonary metastases are rare. These can have a diverse imaging appearance, particularly after chemotherapy. It is important identify patients with solitary skeletal metastases, as they have a better prognosis than those with multiple skeletal or visceral metastases. We describe an unusual case of a solitary metastasis to the femur in a case of colon carcinoma that went undiagnosed and later presented with imaging features of osteogenic sarcoma.

Which is the most optimal technique to spare hippocampus?-Dosimetric comparisons of SCRT, IMRT, and tomotherapy.

AIMS: To evaluate current focal high precision radiotherapy (RT) techniques to spare hippocampi most optimally, in view of mounting clinical evidence to preserve neurocognition. MATERIALS AND METHODS: Computed tomography/magnetic resonance imaging (CT/MRI) datasets of 10 patients with benign/low-grade brain tumors, treated with focal conformal RT were replanned with helical tomotherapy (Tomo), intensity-modulated radiotherapy (IMRT) with high definition multileaf collimator (HD-MLC), and forward planning stereotactic conformal radiotherapy (SCRT). The primary planning objective was to encompass 99% of planning target volume (PTV) by 95% of prescribed dose (54 Gy/30#). Assessments included target coverage (TC), homogeneity index (HI), and maximum (max) and minimum (min) dose. Hippocampal dose was assessed with mean, maximum, minimum, median dosem and various dose levels. RESULTS: Mean V 95 for PTV coverage in Tomo, IMRT, and SCRT were 99.7, 99.4, and 98.3%, respectively. PTV coverage was significantly better in Tomo and IMRT compared to SCRT (P = 0.03). Tomotherapy (HI ≤ 0.06) and IMRT (HI ≤ 0.06) plans were more homogenous than SCRT (HI > 0.7) (P = 0.00). Right hippocampus mean dose with Tomo (20Gy) was 18.5% less than SCRT (30 Gy); but for left hippocampus, difference decreased to 3.3% (Tomo-32.2Gy and SCRT-34Gy). At 30% dose level, 9% more volume of right hippocampus was treated in IMRT and 20% in SCRT when compared to Tomo plan. At 80% dose, 6 and 12% more volumes were treated with IMRT and SCRT, respectively, in comparison to Tomo plan. For left hippocampus all three techniques were comparable. CONCLUSION: Tomotherapy and Linear accelerator (LINAC)-based IMRT achieved significantly better PTV coverage than forward planned SCRT. Tomo as compared to SCRT and IMRT plans showed trend towards significant sparing of the contralateral hippocampus, in eccentrically located tumors.

Neoadjuvant chemotherapy in advanced sinonasal teratocarcinosarcoma with intracranial extension: Report of two cases with literature review.

Sinonasal teratocarcinosarcoma (SNTCS) is a highly aggressive rare tumor of the nasal cavity. Surgery followed by concurrent chemoradiation is the mainstay of treatment in SNTCS. However, intracranial extension may complicate surgical resection, with difficulty in achieving R0 resection. Here we present two cases of SNTCS with intracranial extension; both patients were seen in skull base clinic of our hospital and deemed unsuitable for surgery. These patients then were offered neoadjuvant chemotherapy (NACT), both patients had a partial response with cisplatin and etoposide protocol; subsequently they underwent R0 resection (no macroscopic residual tumor at surgery with all margins were negative for tumor on microscopy). The present cases highlight the fact that NACT with cisplatin and etoposide protocol may be considered in technically unresectable SNTCS.

Neoadjuvant chemotherapy in technically unresectable carcinoma of external auditory canal.

BACKGROUND: Carcinoma of external auditory canal (EAC) is a very rare malignancy with surgical resection as the main modality of treatment. The outcomes with nonsurgical modalities are very dismal. We present a retrospective analysis of 4 patients evaluating the role of neoadjuvant chemotherapy in technically unresectable cancers. MATERIALS AND METHODS: This is a retrospective analysis of 4 patients from our institute from 2010 to 2014 with carcinoma EAC who were deemed unfit for surgery due to extensive disease involving occipital bone with soft tissue infiltration (n = 2), temporal dura (n = 1), left temporal lobe, and extensive soft tissue involvement (n = 1). All these patients received neoadjuvant chemotherapy with docetaxel, cisplatin and 5 fluorouracil (n = 3) and paclitaxel and cisplatin (n = 1). RESULTS: Response evaluation showed a partial response (PR) in 3 and stable disease (SD) in 1 patient by Response Evaluation Criteria in Solid Tumors criteria. All 3 patients who received 3 drug chemotherapy had PR while 1 patient who received 2 drug chemotherapy had SD. Two of these patients underwent surgery, and other 2 underwent definitive chemoradiation. One of 3 patients who achieved PR underwent surgical resection; the other 2 remained unresectable in view of the persistent intradural extension and infratemporal fossa involvement. One patient who had SD could undergo surgery in view of clearance of infraatemporal fossa. Recent follow-up shows that 3 out of these 4 patients are alive. CONCLUSION: This indicates that there may be a role of induction chemotherapy in converting potentially unresectable tumors to resectable disease that could produce better outcomes in carcinoma EAC.

A prospective randomized phase II study comparing metronomic chemotherapy with chemotherapy (single agent cisplatin), in patients with metastatic, relapsed or inoperable squamous cell carcinoma of head and neck.

BACKGROUND: Cetuximab based treatment is the recommended chemotherapy for head and neck squamous cell cancers in the palliative setting. However, due to financial constraints, intravenous (IV) chemotherapy without cetuximab is commonly used in lesser developed countries. We believe that oral metronomic chemotherapy may be safer and more effective in this setting. METHODS: We conducted an open label, superiority, parallel design, randomized phase II trial comparing oral MCT [daily celecoxib (200mg twice daily) and weekly methotrexate (15mg/m(2))] to intravenous single agent cisplatin (IP) (75mg/m(2)) given 3 weekly. Eligible patients had head and neck cancers requiring palliative chemotherapy with ECOG PS 0-2 and adequate organ functions who could not afford cetuximab. The primary end point was progression-free survival. RESULTS: 110 Patients were recruited between July 2011 to May 2013, 57 randomized to the MCT arm and 53 to the IP arm. Patients in the MCT arm had significantly longer PFS (median 101 days, 95% CI: 58.2-143.7 days) compared to the IP arm (median 66 days, 95% CI; 55.8-76.1 days) (p=0.014). The overall survival (OS) was also increased significantly in the MCT arm (median 249 days, 95% CI: 222.5-275.5 days) compared to the IP arm (median 152 days, 95% CI: 104.2-199.8 days) (p=0.02). There were fewer grade 3/4 adverse effects with MCT, which was not significant. (18.9% vs. 31.4%, P=0.14). CONCLUSION: Oral metronomic chemotherapy has significantly better PFS and OS than single agent platinum in the palliative setting.