Prognostic Value of Radiological Extranodal Extension Detected by Computed Tomography for Predicting Outcomes in Patients With Locally Advanced Head and Neck Squamous Cell Cancer Treated With Radical Concurrent Chemoradiotherapy.

Objective: Extra Nodal Extension (ENE) assessment in locally advanced head and neck cancers (LAHNCC) treated with concurrent chemo radiotherapy (CCRT) is challenging and hence the American Joint Committee on Cancer (AJCC) N staging. We hypothesized that radiology-based ENE (rENE) may directly impact outcomes in LAHNSCC treated with radical CCRT. Materials and Methods: Open-label, investigator-initiated, randomized controlled trial (RCT) (2012-2018), which included LAHNSCC planned for CCRT. Patients were randomized 1:1 to radical radiotherapy (66-70 grays) with concurrent weekly cisplatin (30 mg/m2) [cisplatin radiation arm (CRT)] or same schedule of CRT with weekly nimotuzumab (200 mg) [nimotuzumab plus CRT (NCRT)]. A total of 536 patients were accrued and 182 were excluded due to the non-availability of Digital Imaging and Communications in Medicine (DICOM) computed tomography (CT) data. A total of 354 patients were analyzed for rENE. Metastatic nodes were evaluated based on five criteria and further classified as rENE as positive/negative based on three-criteria capsule irregularity with fat stranding, fat invasion, and muscle/vessel invasion. We evaluated the association of rENE and disease-free survival (DFS), loco-regional recurrence-free survival (LRRFS), and overall survival (OS). Results: A total of 244 (68.9%) patients had radiologically metastatic nodes (rN), out of which 140 (57.3%) had rENE. Distribution of rENE was balanced in the two study groups CRT or NCRT (p-value 0.412). The median follow-up period was 39 months (ranging from 35.5 to 42.8 months). Complete response (CR) was seen in 204 (57.6%); incomplete response (IR), i.e., partial response plus stable disease (PR + SD), in 126 (35.6%); and progressive disease (PD) in 24 (6.8%). rENE-positive group had poor survival compared to rENE-negative group 3-year OS (46.7% vs. 63.6%), poor DFS (48.8% vs. 87%), and LRRFS (39.9% vs. 60.4%). rENE positive had 1.71 times increased risk of IR than rENE negative. Overall stage, site, clinical metastatic node (cN), response, and rENE were the significant factors for predicting OS, DFS, and LRRFS on univariate analysis. After making adjustment on multivariate analysis, rENE was an independent prognostic factor for DFS and trending to be significant for OS. Conclusion: Pre-treatment rENE is an independent prognostic marker for survival in patients with LAHNSCC treated radically with CCRT that can be used as a potential predictive marker for response to treatment and hence stratify patients into responders vs. non-responders. We propose the mahajan rENE grading system applicable on CT, magnetic resonance imaging, positron emission tomography-contrast-enhanced CT, and ultrasound.

Is taxane/platinum/5 fluorouracil superior to taxane/platinum alone and does docetaxel trump paclitaxel in induction therapy for locally advanced oral cavity cancers?

BACKGROUND: Cisplatin and 5 fluorouracil drug combination is inferior to the combination of taxane with these 2 drugs. However, often in clinical practice at our center giving TPF (docetaxel, cisplatin, 5 fluorouracil) is difficult in view of logistics and tolerance issues. In such a scenario, we prefer to use the 2 drugs combination of platinum and taxane. However, no study has addressed whether a 2 drugs combination, which includes taxane is inferior to the 3 drugs combination and which the taxane of choice is in the 2 drugs combination of taxane and platinum. METHODS: This is a retrospective analysis of prospectively collected data of patients undergoing induction chemotherapy (IC) in oral cavity cancers from 2010 to 2012. We chose for analysis those patients who had a baseline scan done within 4 weeks of starting therapy and a follow-up scan done within 2 weeks of completion of the second cycle of IC. Response was scored in accordance with RECIST version 1.1. Chi-square analysis was done to compare response rates (RRs) between regimens. RESULTS: Two hundred and forty-five patients were identified. The median age was 45 years (24-70 years), 208 (84.9%) were male patients, and 154 patients (62.9%) had primary in the Buccal mucosa. The regimens received were TPF 22 (9%), docetaxel + cisplatin 97 (39.6%), paclitaxel + cisplatin 89 (36.3%), docetaxel + carboplatin 16 (6.5%) and paclitaxel + carboplatin 21 (8.6%). The overall RRs were complete response, partial response, stable disease and progressive disease in 4 (1.6%), 56 (22.9%), 145 (59.2%) and 40 (16.3%). The 3 drugs regimen (TPF) had 50% RR as compared to 22% RR with 2 drugs regimen (P = 0.004). Docetaxel containing regimens had 30.3% RR as compared to 17.2% RR with paclitaxel containing regimens (P = 0.094). CONCLUSIONS: TPF has better RR than a 2 drugs taxane-containing regimen and docetaxel leads to a better RR than paclitaxel for IC in locally advanced oral cavity cancers.

Referral pattern for neoadjuvant chemotherapy in the head and neck cancers in a tertiary care center.

BACKGROUND: Use of any treatment modality in cancer depends not only on the effectiveness of the modality, but also on other factors such as local expertise, tolerance of the modality, cost and prevalence of the disease. Oropharyngeal and laryngeal cancer are the major subsites in which majority of neoadjuvant chemotherapy (NACT) literature in the head and neck cancers is available. However, oral cancers form a major subsite in India. MATERIALS AND METHODS: This is an analysis of a prospectively maintained data on NACT in the head and neck cancers from 2008 to 2012. All these patients were referred for NACT for various indications from a multidisciplinary clinic. Descriptive analysis of indications for NACT in this data base is presented. RESULTS: A total of 862 patients received NACT within the stipulated time period. The sites where oral cavity 721 patients (83.6%), maxilla 41 patients (4.8%), larynx 33 patients (3.8%), laryngopharynx 8 patients (0.9%) and hypopharynx 59 patients (8.2%). Out of oral cancers, the major indication for NACT was to make the cancer resectable in all (100%) patients. The indication in carcinoma of maxilla was to make the disease resectable in 29 patients (70.7% of maxillary cancers) and in 12 patients (29.3% of maxillary cancers) it was given as an attempt to preserve the eyeball. The indication for NACT in laryngeal cancers was organ preservation in 14 patients (42.4% of larnyngeal cancer) and to achieve resectability in 19 patients (57.6% of larnyngeal cancer). The group with laryngopharynx is a cohort of eight patients in whom NACT was given to prevent tracheostomy, these patients had presented with early stridor (common terminology criteria for adverse events Version 4.02). The reason for NACT in hypopharyngeal cancers was for organ preservation in 24 patients (40.7% of hypopharyngeal cancer) and for achievement of resectability in 35 patients (59.3% of hypopharyngeal cancer). CONCLUSION: The major indication for NACT is to make disease resectable at our center while cases for organ preservation are few.

Oral metronomic scheduling of anticancer therapy-based treatment compared to existing standard of care in locally advanced oral squamous cell cancers: A matched-pair analysis.

CONTEXT: Head and neck cancers in developing countries present with advanced disease, compounded by poor access to tertiary care centers. AIM: We evaluated oral metronomic scheduling of anticancer therapy (MSAT) in advanced operable oral cancers, in conjunction with standard therapy. SETTINGS AND DESIGN: This was a retrospective matched-pair analysis carried out in a tertiary referral cancer center. MATERIALS AND METHODS: Advanced operable oral cancer patients having a waiting period for surgery > 3 weeks were administered MSAT. Patients then underwent standard therapy (surgery +/- adjuvant radiation/chemoradiation) as warranted by the disease, followed by MSAT maintenance therapy. Outcomes of the MSAT group were compared with stage-matched controls with similar waiting periods. STATISTICAL ANALYSIS: Survivals were found using the Kaplan-Meier method and compared between groups using the log rank test. RESULTS: Response was seen in 75% of 32 patients. Two-year disease-free survivals (DFS) in MSAT and control groups were 86.5 and 71.6%, respectively. Two-year DFS in MSAT group who received at least three months of MSAT was 94.6% (P = 0.03). CONCLUSIONS: Oral MSAT is an economical, effective, and safe adjuvant therapy for oral cancers. It has the potential for preventing progression of the disease and improving DFS.

Cut margins and disease control in oral cancers.

AIM: This retrospective study was done to evaluate the impact of cut margins on disease-free survival in patients with previously untreated oral squamous cell cancers. MATERIALS AND METHODS: Records of 306 cases were reviewed for clinical details and status of margins at resection. The independent influence of margins on recurrence was analyzed. The impact of frozen section analysis on achieving free margins was also examined. RESULTS: 190 (62.1%) patients had negative margins of resection (≥ 5 mm), 102 (33.3%) patients had close margins (1-5 mm), while 14 (4.6%) patients had positive margins (≤ 1 mm). The median follow-up for the entire cohort was 26.5 months. There were 79 (25.8%) recurrences, of which, 46 (58.2%) were local, 9 (11.3%) were locoregional, 16 (20.2%) were regional, and 8 (10.1%) were distant metastasis. 42 (22.2%) cases with negative margins developed a recurrence as compared to 31 (30.4%) cases with close margins and 6 (42.8%) cases with positive margins (P value 0.01). Average time to recurrence in case of negative margins was 34.8 months, for close margins was 33.9 months, while in those with positive margins was 10.18 months (P value 0.002). Close and positive margins were found to be significantly associated with increased local recurrence (P values 0.01 and 0.03, respectively) and with overall recurrence (P values 0.003 and 0.003, respectively). Frozen section was seen to influence margins in 20.4% cases. CONCLUSION: Margins are an important predictor of disease control. The surgeon must aim for adequate margins at initial resection.

Current status of near-total laryngectomy: review.

Concurrent chemoradiation is currently the accepted 'standard of care' for locally advanced laryngeal and hypopharyngeal cancers. However, there is a subset of patients not suitable for chemoradiation, in whom primary surgery is the best option. Speech preservation is of prime importance in these patients. Near-total laryngectomy is a voice-preserving procedure which can be considered as an alternative to total laryngectomy for selected patients with lateralised, locally advanced cancers of the larynx and hypopharynx. Although these patients are left with a permanent tracheostomy, lung-powered speech is maintained by way of a dynamic shunt created from the uninvolved tissues of the larynx. Since its first description in the early 1980s, the procedure has been shown by various authors to be oncologically sound, with high success rates. Unfortunately, the procedure has not gained wide acceptance due to perceived fears of surgical complexity. In this review, we discuss the various issues related to the procedure and we review the relevant literature.

Bisphosphonate induced osteonecrosis of the jaw masquerading as tumor: a word of caution for oral surgeons and oncologists.

AIMS: To highlight the misdiagnosis or delay in the detection of Bisphosphonate induced necrosis of Jaw (BINJ). It is associated with prolonged administration of intravenous bisphosphonates that are routinely used in the management of osteoporosis, Paget's disease, Multiple Myeloma, bone metastases. It improves quality of life, delays the skeletal complication, decreases the pain and hypercalcemia. METHODS: We prospectively collected data of those patients who were receiving bisphosphonates for management of their primary illness and developed BINJ. This pathology being a new entity most oncologists are still ignorant about its existence. RESULTS: Use of intravenous bisphosphanates can lead to BINJ which may mimic malignancy or metastasis. None of our patients were counseled, oncologists did not perform routine oral examinations, dentists went ahead with unwarranted interventions, radiologist raised false alarm and oral surgeons undertook unnecessary biopsies. Misled by clinical presentation and radiological appearance, all patients were initially misdiagnosed and underwent unwarranted interventions. CONCLUSIONS: A careful dental clinical examination and appropriate imaging study is recommended before starting bisphosphonate therapy. The doctors prescribing Bisphosphonates especially intravenous preparations should not only counsel the patients but also routinely examine patient's oral cavity.

Epidermal inclusion cyst of the styloid process: a case report.

We report an unusual case of epidermal inclusion cyst of the styloid process which presented to us with decreased hearing and tinnitus. The patient underwent complete excision via a combined postaural cervical approach. The unusual location of the tumor and the absence of a history of trauma or intervention in that area added confusion to the diagnosis, which was finally made on histopathology.

In vitro chemosensitivity profile of oral squamous cell cancer and its correlation with clinical response to chemotherapy.

CONTEXT: Oral cancers represent a disparate group of tumors with diverse clinical behavior and chemosensitivity profile. Currently, it is difficult to predict whether a tumor will respond to chemotherapy and which drug(s) will achieve the maximum clinical response. AIMS: To study in vitro chemosensitivity profile of oral cancers and to correlate the in vitro chemosensitivity of oral cancer to clinical response to chemotherapy. SETTINGS AND DESIGN: Prospective study in a tertiary cancer care center. METHODS AND MATERIAL: We prospectively studied the chemosensitivity profile of 57 untreated, advanced, unresectable oral cancers to cisplatin, methotrexate, 5-fluorouracil and their combinations by using histoculture drug response assay (HDRA) and correlated them to the clinical response to chemotherapy. STATISTICAL ANALYSIS USED: Chi Square test. RESULTS: Biopsy samples were successfully histocultured in 52/57 (91%) cases. Of these 52 evaluable patients, 47 had primary gingivo-buccal cancers and five had tongue / floor of mouth cancers. Based on the assay, 27 (52%) tumors were sensitive to cisplatin, 27 (52%) to methotrexate, 24 (46%) to 5-fluorouracil, 38 (73%) to combination of cisplatin and methotrexate and 36 (69%) to combination of cisplatin and 5-fluorouracil. Of these, 31 patients with good performance status received two cycles of chemotherapy using one or more of these test drugs. There was a significant correlation (p=0.03) between the in vitro chemosensitivity and the clinical response. Negative predictive value of the test was 80%, positive predictive value-69%, sensitivity-79% and specificity -71%. The overall accuracy of the assay was 74%. CONCLUSIONS: We found HDRA to be a fairly good predictor of chemo-response of oral cancer.

Split therapy: planned neck dissection followed by definitive radiotherapy for a T1, T2 pharyngolaryngeal primary cancer with operable N2, N3 nodal metastases--a prospective study.

BACKGROUND: The management of patients with a small pharyngolaryngeal cancer (T1 and T2) with large nodal metastases is a subject of debate. We present data on the feasibility and outcome of treating these patients with surgery for the nodal metastases followed by definitive radiotherapy. METHODS: Prospective study of 59 patients of small pharyngolaryngeal primary squamous carcinomas with operable (N2/N3) nodal metastasis treated with neck dissection followed by radiotherapy. RESULTS: Complete nodal clearance was achieved in 54 (90%). The mean nodal size was 4 cm and extranodal extension was seen in 88% of patients in the study group. There were no significant postoperative complications. Median interval between surgery and radiotherapy was 23 days. Forty-nine patients (83%) started their RT within 6 weeks of surgery. With a median follow-up of 25 months, the disease free and overall survival was 54% and 60% (5 years). CONCLUSION: The management of patients with a radiocurable pharyngolaryngeal primary with large nodes by this approach is a feasible option with adequate control and survival.

Simultaneous reconstruction of large skin and mucosal defect following head and neck surgery with a single skin paddle pectoralis major myocutaneous flap.

The pectoralis major myocutaneous (PMMC) flap is commonly used for head and neck reconstruction especially in impoverished nations. PMMC is a sturdy pedicled flap with relatively fewer complications, the learning curve is short and no specialized training in microvascular surgery is needed in order to use this flap. In a defect that requires a large skin and mucosal lining the authors routinely use either a bi-paddle PMMC or a combination of PMMC (for the mucosal lining) and a delto-pectoral flap (for the skin defect). It is indisputable that free tissue transfer is a better way of reconstruction for the majority of most such defects. Unfortunately, not all patients can be offered this form of reconstruction due to the cost, time, expertise and infrastructural constraints in high volume centres such as ours. Bi-paddling of PMMC is hazardous in obese males and most female patients. In such patients the skin defect is reconstructed usually by the delto-pectoral (DP) flap but this, for obvious reasons, is less welcomed by the patients. The authors suggest a technique wherein mucosal lining is created by the myofascial lining (inner surface) of the flap and the skin defect is reconstructed by the skin paddle of the single paddle PMMC. It should be considered wherever a DP flap is unacceptable, or bi-paddling or free tissue transfer is not possible.

Alveolar soft part sarcoma of the head and neck.

Alveolar soft part sarcoma (ASPS) of the head and neck region has been a rarely reported entity. These lesions have a high propensity for distant metastasis. A retrospective study of the medical records at our institute, revealed thirty-eight cases of ASPS. Six of these were of primary head and neck origin. The article highlights the aggressive nature of the tumour and the need to arrive at a consensus on the treatment protocol.

A prospective study of pharyngocutaneous fistulas following total laryngectomy.

Pharyngocutaneous (PC) fistula is a common complication following laryngectomy. It leads to increased morbidity, delay in adjuvant treatment, prolonged hospitalization and an increase in treatment costs. Although a number of factors that result in PC fistula have been described, there is still no agreement on the most significant factors. We undertook a prospective study to critically analyze PC fistula and its association with various tumors, patient and treatment related factors. This was a prospective study that included 143 patients who underwent laryngeal surgery for squamous cell carcinoma of the larynx and pyriform sinus. Use of pectoralis major myocutaneous flap to reconstruct the neopharynx, primary disease in pyriform and extensive soft tissue infiltration were significantly associated with PC fistula. Prior treatment (radiotherapy and chemotherapy), type of closure (T closure, Y closure and vertical closure), Layers of closure (full thickness interrupted, submucosal interrupted, submucosal continuous) type of suture material (silk, vicryl ), age, sex, stage, preoperative tracheostomy, cut margin status, pre/postoperative hemoglobin and experience of surgeons did not relate significantly.

Quality of life of head and neck cancer patient: validation of the European organization for research and treatment of cancer QLQ-C30 and European organization for research and treatment of cancer QLQ-H&N 35 in Indian patients.

AIMS: To present the first cross-culture validation of the European organization for research and treatment of cancer (EORTC) quality of life questionnaires, the EORTC-QLQ-C30, and the QLQ-H&N 35 in India. SETTINGS AND DESIGN: These questionnaires were translated into two vernacular languages and pilot test was done on 15 patients. Two hundred head and neck cancer patients completed the QLQ-C30 and the QLQ-H&N 35 at two time points during their treatment. Psychometric evaluation of the structure, reliability, and validity of the questionnaire was undertaken. RESULTS: The data supports the reliability of the scales. Validity was tested by item-scale, scale--scale correlation and by performing known group comparisons. The results demonstrated that the items correlated with their respective scale and no significant correlation was found between scales. The questionnaire was responsive to change over a period of time. SUMMARY: This data suggests that the EORTC QLO-C30 and the QLQ-H&N 35 are reliable and valid questionnaires when applied to a sample of head and neck cancer patients in India.

Follicular dendritic cell tumour of tonsil - is it an under-diagnosed entity?

Neoplasms of follicular dendritic cells are uncommon and while majority of them occur in lymph nodes, they are increasingly recognized at varied sites such as abdominal viscera. Tonsil is the most common extra nodal site for occurrence of FDCT in the head and neck region. We describe three cases of follicular dendritic cell tumour occurring in the tonsil.

Surgical treatment outcomes of localized squamous carcinoma of buccal mucosa.

BACKGROUND: The purpose of the study was to analyze the outcomes after surgical therapy (peroral wide excision) for early squamous carcinoma of the buccal mucosa. METHODS: This is a retrospective study of localized squamous carcinoma of the buccal mucosa treated with peroral wide excision at a major tertiary-care hospital. RESULTS: A total of 147 consecutive patients were analyzed. One hundred eight patients (73.5%) had no recurrence, whereas 18 (12.2%) had a local recurrence, 11 (7.5%) had regional metastasis, and 10 (6.8%) had locoregional recurrence over a median follow-up of 46 months. Most patients with local recurrences (15 patients, 83.3%) and regional metastases (eight patients, 72%) could be salvaged with treatment. In contrast, only four patients (40%) with locoregional recurrence could be salvaged. Most of the recurrences in this study group occurred within 2 years of primary treatment (29 [74%] of 39 patients). Three-year actuarial overall survival rate and disease-free survival rates were 91% and 77%, respectively. CONCLUSIONS: Peroral wide excision seems to be an adequate procedure for early squamous carcinoma of buccal mucosa. Histologic grade of the tumor emerged as the only prognostic factor of significance for recurrence in this study.

Effective rehabilitation after partial glossectomy.

OBJECTIVE: The surgical treatment of cancer of tongue results in speech deficits. Speech disorders in the glossectomised patients fall into, categories of impaired articulation, reduced speech intelligibility, altered oral & nasal resonance, impaired voice quality & reductions in global speech proficiency. Since speech is a social tool, its most significant measurements start with the degree to which it can be understood. METHODS: This study was conducted at Tata Memorial Hospital, Mumbai, India, An incidental sample of 25 patients was selected for this study. Different questionnaires specially devised for this study were used to assess patients' speech & deglutition post-operatively. The data was collected 3 months after surgery of these patients. RESULTS: Studies have indicated that larger the segment of the tongue, the greater is the distortion of speech & difficulty in deglutition. All functions associated with the interaction of the tongue with the related anatomy of the head & neck were severely impaired following glossectomy. The rehabilitation plan for partial glossectomy patients depended upon the assessment of their post-operative articulation level, education, job, age, family & motivation.