Survival Outcomes and Patterns of Failure in Maxillary Alveolus Squamous Cell Carcinoma.

Introduction Squamous cell carcinoma (SCC) of the maxillary alveolus is a relatively rare disease. There is lack of data on this subsite as compared with other sites. The factors that affect survival in cases of maxillary alveolar SCC are tumor stage, local and cervical metastases, histological grading, and the margin status. Objectives To evaluate the overall survival (OS), the disease free survival (DFS), and the complex interaction and effects of margin status, histological differentiation, habits (such as smoking and the use of smokeless tobacco products), and cervical and distant metastases based on clinicopathological data. Methods We examined the electronic database at our hospital from 2003 to 2017. We included all cases with a histopathological diagnosis of SCC of the maxillary alveolus. Tumors originating primarily from the maxillary alveolus were included, while those originating from adjacent subsites, like the hard palate, the buccal mucosa or the maxillary sinus were excluded. We also excluded all the patients who were not operated on with a curative intent. Results More than half of the patients had stage-IV tumors at the time of presentation, while only one fourth of them had nodal metastasis. The rate of recurrence increased in cases of primary tumors in advanced stages and the degree of histological differentiation. The 2-year and 5-year OS rates were of 54.5% (18 patients) and 30.3% (10 patients) respectively. Conclusion Primary tumors in advanced stages, histological grade, and presence of nodal metastasis are poor prognostic markers in terms of long-term survival.

Long-Term Disease Control of Locally Invasive Epithelial-Myoepithelial Carcinoma of Parapharyngeal Salivary Glands With Definitive Radiotherapy.

Epithelial-myoepithelial carcinoma (EMC) is a rare clinical entity that affects glandular tissues, most commonly salivary glands. EMC of parapharyngeal space is exceedingly rare. Surgery is the mainstay of treatment with or without chemotherapy, radiotherapy, or both. Due to the rarity of the disease, select cases where surgery is not possible present a management conundrum. We present a case of locally advanced, stage IVa EMC of parapharyngeal space that was treated with upfront definitive radiotherapy. Radiotherapy treatment alone led to long-term disease control in both clinical and radiological follow-ups. The patient was followed for more than eight years posttreatment with no disease recurrence, enjoying the normal activities of life with no late toxicities including xerostomia. This case report highlights the role of radiotherapy in the management of such patients, and more studies are required in this context for surgical candidates with positive disease margins.

Survival Outcomes and Patterns of Failure in Maxillary Alveolus Squamous Cell Carcinoma

Abstract Introduction Squamous cell carcinoma (SCC) of the maxillary alveolus is a relatively rare disease. There is lack of data on this subsite as compared with other sites. The factors that affect survival in cases of maxillary alveolar SCC are tumor stage, local and cervical metastases, histological grading, and the margin status. Objectives To evaluate the overall survival (OS), the disease free survival (DFS), and the complex interaction and effects of margin status, histological differentiation, habits (such as smoking and the use of smokeless tobacco products), and cervical and distant metastases based on clinicopathological data. Methods We examined the electronic database at our hospital from 2003 to 2017. We included all cases with a histopathological diagnosis of SCC of the maxillary alveolus. Tumors originating primarily from the maxillary alveolus were included, while those originating from adjacent subsites, like the hard palate, the buccal mucosa or the maxillary sinus were excluded. We also excluded all the patients who were not operated on with a curative intent. Results More than half of the patients had stage-IV tumors at the time of presentation, while only one fourth of them had nodal metastasis. The rate of recurrence increased in cases of primary tumors in advanced stages and the degree of histological differentiation. The 2-year and 5-year OS rates were of 54.5% (18 patients) and 30.3% (10 patients) respectively. Conclusion Primary tumors in advanced stages, histological grade, and presence of nodal metastasis are poor prognostic markers in terms of long-term survival.

Treatment Outcomes of Maxillary Sinus Squamous Cell Carcinoma at a Dedicated Cancer Institute: A Retrospective Study.

Introduction Squamous cell carcinoma arising at the maxillary sinus is a rare neoplasm, characterized by an aggressive growth pattern and glooming prognosis. The proximity of the maxillary sinus with complex anatomical structures such as the eye, skull base, infratemporal fossa, pterygomaxillary fossa, nasal cavities, and ethmoid sinuses makes the surgical treatment of tumors infiltrating into these structures very challenging. The study's objective was to investigate the prognostic factors of survival and maxillary sinus SCC treatment outcomes. Methods We did a retrospective analysis of patients treated for maxillary sinus SCC at our institution between 2004 -2018. The study included all the patients with histologically proven maxillary sinus SCC treated with curative intent. The medical record of 43 patients was reviewed and utilized for the analysis. The Kaplan-Meier curve calculated five-year overall survival. Results A total of 43 patients were analyzed. At the presentation time, the mean age was 54.56 years (SD ± 11.65). Smoking (n=13, 30.2%) was the common risk factor. 36 (83.7%) patients presented with stage IV disease. Surgery was performed in 16 (37.2%) patients, whereas 27 (62.8%) patients received radiation and chemotherapy. Treatment failure was seen in 35 (81.4%) patients with locoregional recurrence in 30 (85.7%) patients and distant metastases in 5 (14.3%) patients. The five years overall survival in our study was 22%. Loco-regional recurrence and distant metastasis were the significant factors impacting survival (p=0.01). Conclusion Maxillary sinus SCC is rare cancer that is more common in males and usually presents at an advanced stage with a poor outcome. These tumors have a higher rate of treatment failure with a poor prognosis. Locoregional recurrence and distant metastasis adversely impact the overall survival.

Mammary analogue secretory carcinoma of parotid gland: Literature review and experience of a dedicated cancer institution in Pakistan.

Mammary Analogue Secretory Carcinoma (MASC) is a rare pathology of the salivary gland, most commonly involving the parotid gland. The objective of this study was to identify the characteristic features of MASC and its treatment outcomes. A retrospective review of 12 patients with histological diagnosis of MASC, who were managed between 2010 to 2019, was carried out at the Shaukat Khanum Memorial Cancer Hospital & Research Centre, Lahore. Their mean age was 34±16 years. There were 9 (75%) male and 3 (25%) female patients. Painless slow growing swelling was the most common presenting symptom. All the patients had undergone surgical excision with or without neck dissection, followed by adjuvant treatment. Of these, six patients had T2 tumours, while four had cervical lymph node metastasis. The mean follow-up period was 23±21 months. Local recurrence was seen in one patient. MASC is considered a low-grade tumour with good prognosis which can be treated with curative intent of surgery followed by radiotherapy effectively.

A digital score of tumour-associated stroma infiltrating lymphocytes predicts survival in head and neck squamous cell carcinoma.

The infiltration of T-lymphocytes in the stroma and tumour is an indication of an effective immune response against the tumour, resulting in better survival. In this study, our aim was to explore the prognostic significance of tumour-associated stroma infiltrating lymphocytes (TASILs) in head and neck squamous cell carcinoma (HNSCC) through an AI-based automated method. A deep learning-based automated method was employed to segment tumour, tumour-associated stroma, and lymphocytes in digitally scanned whole slide images of HNSCC tissue slides. The spatial patterns of lymphocytes and tumour-associated stroma were digitally quantified to compute the tumour-associated stroma infiltrating lymphocytes score (TASIL-score). Finally, the prognostic significance of the TASIL-score for disease-specific and disease-free survival was investigated using the Cox proportional hazard analysis. Three different cohorts of haematoxylin and eosin (H&E)-stained tissue slides of HNSCC cases (n = 537 in total) were studied, including publicly available TCGA head and neck cancer cases. The TASIL-score carries prognostic significance (p = 0.002) for disease-specific survival of HNSCC patients. The TASIL-score also shows a better separation between low- and high-risk patients compared with the manual tumour-infiltrating lymphocytes (TILs) scoring by pathologists for both disease-specific and disease-free survival. A positive correlation of TASIL-score with molecular estimates of CD8+ T cells was also found, which is in line with existing findings. To the best of our knowledge, this is the first study to automate the quantification of TASILs from routine H&E slides of head and neck cancer. Our TASIL-score-based findings are aligned with the clinical knowledge, with the added advantages of objectivity, reproducibility, and strong prognostic value. Although we validated our method on three different cohorts (n = 537 cases in total), a comprehensive evaluation on large multicentric cohorts is required before the proposed digital score can be adopted in clinical practice. © 2021 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Outcomes of Management of Sinonasal Malignancies at a Dedicated Cancer Institution: A Retrospective Study.

INTRODUCTION: Sinonasal malignancies (SNMs) are a rare and heterogeneous group of cancers with an incidence of 3%-5% of all head-and-neck tumours. The aim of the present study was to identify the characteristic features of SNMs and to analyze the treatment outcomes and the prognostic factors affecting it. MATERIALS AND METHODS: A retrospective review of patients with SNM treated at a dedicated cancer center of Pakistan between 2004 and 2018 was carried out. All patients with histologically proven diagnosis of malignancy arising from nasal cavity or paranasal sinuses and being treated with curative intent were included. The medical records of 184 cases were utilized for final analysis. Chi-square test was applied to identify significant differences. Five-year disease-specific survival (DSS) was calculated using Kaplan-Meier curve via log-rank test and comparison was made between squamous and nonsquamous histologies. P ≤0.05 was considered statistically significant. RESULTS: Squamous cell carcinoma was the most common histopathology (n = 62, 33.7%). 130 (70.7%) patients presented with stage IV disease. Nodal metastasis was seen in 24 (13%) patients. Treatment failure was seen in 96 (52.2%) patients and was significantly associated with tumour size and the overall stage. DSS of patients with squamous cell carcinoma was 29% as compared to 52% for patients with nonsquamous histologies (P = 0.001). DISCUSSION: SNM is a diverse group of cancers presenting in late stages. A higher rate of treatment failure associated significantly with stage of the disease was identified in our study.

Impact of Previous Irradiation on Wound Healing after Negative Pressure Wound Therapy in Head and Neck Cancer Patients-A Systematic Review.

(1) Background: Negative pressure wound therapy (NPWT) has been effectively used for wound management in comparison to traditional dressings. The purpose of this study was to provide an evidence-based review of NPWT in head and neck cancer patients, as well as the impact of previous irradiation and other risk factors on wound healing. (2) Material and Methods: We conducted a comprehensive search in PubMed, Medline, Embase, Web of Science, and Cochrane Library databases for relevant literature. (3) Results: 15 studies fulfilled the inclusion criteria. The most common etiologies requiring NPWT were defects post tumor resection and flap reconstruction and oro/pharyngo-cutaneous fistulas. The neck was found to be the most common site of involvement (47.3%). The overall wound healing response rate was 87.5%. The median negative pressure recorded was 125 mm of Hg, with a median dressing change time of three days. Previous irradiation (p = 0.01; OR = 4.07) and diabetes mellitus (DM) (p = 0.001; OR = 5.62) were found to be significantly associated with delayed wound healing after NPWT. (4) Conclusion: NPWT treats complex wounds in head and neck cancer patients and should represent a significant armamentarium in head and neck cancers. Previous irradiation and DM have detrimental effects on wound healing after NPWT.

Prognostic outcomes of treatment naïve oral tongue squamous cell carcinoma (OTSCC): a comprehensive analysis of 14 years.

OBJECTIVES: To analyze the factors predicting survival outcomes in treatment naïve oral tongue squamous cell carcinoma (OTSCC). MATERIALS AND METHODS: A comprehensive review of 531 oral tongue carcinoma patients treated with upfront surgery followed by adjuvant radiotherapy or chemoradiotherapy was conducted from 2004-2018. RESULTS: The mean age of presentation was 53 years (11-86) with a male to female ratio of 1.3:1. The associated risk factors were smoking (21%), betel nut (16%), naswar (9%) and alcohol (1%). Most of the cases were either well (45.1%) or moderately (46.2%) differentiated. Surgery was performed in 164 patients alone while 368 were treated with surgery in combination with adjuvant modalities. Overall (OS) and disease free survival (DFS) were 66 and 71%, respectively, with a median follow up of 2.5 years. Cox regression analysis showed nodal positivity, increased depth of invasion (DOI) and higher lymph node ratio (LNR) as significant prognosticators impacting OS and DSS. CONCLUSION: Nodal volume, DOI and LNR are the most consistent predictors of poor outcome in OTSCC. Nodal positivity, depth of invasion > 5 mm and lymph node ratio > 0.04 adversely affect OS and DSS.

Prevalence of pain in oral cancer: A retrospective study.

OBJECTIVE: This study aimed to estimate the prevalence of pain among treatment-naïve patients with oral cancer and to identify the clinical and histopathological characteristics of oral cancer associated with pain occurrence. MATERIALS AND METHODS: A retrospective chart review was conducted of patients presenting with biopsy-proven oral cancer between January 2015 and December 2019. Variables, including demographic data, medical history, clinical presentation, and histopathological information, were extracted and analyzed. Appropriate descriptive and analytic statistics were computed. RESULTS: Among 1,067 participants, 682(63.9%) were males. The prevalence of pain was 67.5%. It was found to be significantly associated with the duration of symptoms, history of betel or areca nut, squamous cell carcinoma, presence of disease in tongue, palate, and lips, lesion size, clinical nodal involvement, depth of invasion, TNM classification, limited mouth opening, bleeding, and restricted tongue mobility. Logistic regression analysis suggested that pain in oral cancer was positively associated with the occurrence of disease in the tongue and negatively with TNM stage I. CONCLUSIONS: There is a high prevalence of pain among patients with oral cancer even before the initiation of any therapeutic intervention. Occurrence is significantly higher in patients with the presence of disease in the tongue and among those with TNM stage II or more.

Acquiring guideline-enabled data driven clinical knowledge model using formally verified refined knowledge acquisition method.

BACKGROUND AND OBJECTIVE: Validation and verification are the critical requirements for the knowledge acquisition method of the clinical decision support system (CDSS). After acquiring the medical knowledge from diverse sources, the rigorous validation and formal verification process are required before creating the final knowledge model. Previously, we have proposed a hybrid knowledge acquisition method with the support of a rigorous validation process for acquiring medical knowledge from clinical practice guidelines (CPGs) and patient data for the treatment of oral cavity cancer. However, due to lack of formal verification process, it involves various inconsistencies in knowledge relevant to the formalism of knowledge, conformance to CPGs, quality of knowledge, and complexities of knowledge acquisition artifacts. METHODS: This paper presents the refined knowledge acquisition (ReKA) method, which uses the Z formal verification process. The ReKA method adopts the verification method and explores the mechanism of theorem proving using the Z notation. It enhances a hybrid knowledge acquisition method to thwart the inconsistencies using formal verification. RESULTS: ReKA adds a set of nine additional criteria to be used to have a final valid refined clinical knowledge model. These criteria ensure the validity of the final knowledge model concerning formalism of knowledge, conformance to GPGs, quality of the knowledge, usage of stringent conditions and treatment plans, and inconsistencies possibly resulting from the complexities. Evaluation, using four medical knowledge acquisition scenarios, shows that newly added knowledge in CDSS due to the additional criteria by the ReKA method always produces a valid knowledge model. The final knowledge model was also evaluated with 1229 oral cavity patient cases, which outperformed with an accuracy of 72.57% compared to a similar approach with an accuracy of 69.7%. Furthermore, the ReKA method identified a set of decision paths (about 47.8%) in the existing approach, which results in a final knowledge model with low quality, non-conformed from standard CPGs. CONCLUSION: ReKA refined the hybrid knowledge acquisition method by discovering the missing steps in the current validation process at the acquisition stage. As a formally proven method, it always yields a valid knowledge model having high quality, supporting local practices, and influenced by standard CPGs. Furthermore, the final knowledge model obtained from ReKA also preserves the performance such as the accuracy of the individual source knowledge models.

Locally Advanced Oral Tongue Cancer: Is Organ Preservation a Safe Option in Resource-Limited High-Volume Setting?

BACKGROUND: Oral tongue is found to be the most common intraoral subsite with worse prognosis despite the use of multimodality treatments. Extensive resections have resulted in loss of form and function of tongue in advanced tumors. The objective of the study was to analyze the role of induction chemotherapy (IC) in intermediate to advanced staged oral tongue cancer for organ preservation and survival outcome in a developing country. MATERIALS AND METHODS: The records of oral tongue cancer patients treated from 2007 to 2016 were retrospectively analyzed. RESULTS: Eighty-one oral tongue cancer patients with advanced stage were treated using induction arm in 10 years. The median follow-up was 24 months with 3- and 5-year survival of 77% and 58%, respectively. IC has an overall response in 87% of the patients at primary site. The chemotherapy has completely resolved the nodal disease in 17% of the patients, but 23% of the patients had failed to respond. Only 21% of the patients received reconstruction using local or regional flaps. CONCLUSION: IC has shown encouraging results in advanced staged oral tongue cancers with function preservation and improved survival outcome in less privileged high-volume centers.

Incidence of thyroid gland invasion in advanced laryngeal cancers and its impact on disease-specific survival; a retrospective review at a tertiary care center.

Background: Incidence of thyroid gland invasion in advanced laryngeal cancers is low. Ipsilateral or total thyroidectomy along with total laryngectomy has been controversial and there has been no consensus over the management of thyroid gland in advanced laryngeal cancers.Objective: To determine the frequency of thyroid gland invasion in locally advanced laryngeal squamous cell carcinoma and the risk factors associated with it.Material and methods: A retrospective review of patients with laryngeal squamous cell carcinoma operated at our center between January 2011 and December 2018 was carried out. Patients undergoing upfront or salvage laryngectomy with or without neck dissection along with hemi or total thyroidectomy were included. Histopathology reports were reviewed to record the involvement of thyroid gland.Results: Invasion of thyroid gland by squamous cell carcinoma larynx was seen in 10 (10.9%) patients out of 92. All of the cases showed direct extension of the tumor. Trans-glottic, subglottic, and tumors with extra laryngeal spread were found to be significantly associated with thyroid gland invasion. Patients with thyroid gland invasion showed higher rate recurrence.Conclusion and significance: Incidence of thyroid gland invasion in squamous cell carcinoma larynx is low, allowing us not to address thyroid routinely in patients undergoing total laryngectomy for laryngeal carcinoma.

Pre-operative Occurrence of First Bite Syndrome in Two Cases of Parotid Gland Tumour.

Introduction: First bite syndrome (FBS) is a gustatory-evoked painful condition that is characterised by the onset of severe electric shock-like pain in the periauricular region. In the majority of patients, FBS develops postoperatively. However, in rare instances, it may present in a pre-operative setting. Case Description: Two cases of FBS developing preoperatively secondary to parotid gland tumour are presented. The patients, 54 and 30 years old, presented with complaints of electric shock-like pain localised over the periauricular region. In each case, the pain was triggered following the first bite of the meal. In both cases, the pain lasted for few seconds and with subsequent bites subsided only to return at the beginning of the next meal. Practical Implications: Pre-operative occurrence of FBS in the absence of a history of trauma or surgery should necessitate a thorough investigation and follow-up for an underlying salivary gland tumour.

Reasons for Admission and Outcome to an Acute Palliative Care Unit in Patients with Advanced Malignancy in a Cancer Hospital.

Introduction: The alleviation of suffering is a primary goal of palliative care team for patients with terminal cancer. In some cases, patients experience symptoms requiring inpatient care. The purpose of this investigation was to assess the clinical presentation and outcomes of hospitalisation in patients that were admitted to the acute palliative care service. Materials and Methods: This is a retrospective descriptive study looking at admissions to an acute palliative care unit in a single centre over a 24-month period. Medical records of all patients, admitted in palliative care unit from 1 January, 2013, to 31 December, 2014, were reviewed for reason of admission and outcome. Results: A total of 226 patients were identified and included in the present investigation. Among these, 55.5% (125) were females. The median age of the cohort was 48 (15-86) years. The most common reasons for admission were alteration in consciousness (19.5%), respiratory tract infection (18%), diarrhoea and/or vomiting (14.2%) and respiratory distress (not related to infection) (13.4%). The median duration of hospital stay was 4 (0- 27) days. The majority of the patients were discharged home (65.1%). However, a significant portion (33.1%) of the patients did not survive the hospitalisation. Following discharge from the hospital, at 4-weeks follow-up, the survival rate was 38.7%. This dropped to 21.7% at 8-weeks. Conclusion: Patients with advanced disease have a multitude of reasons to seek acute inpatient care. The majority of the patients were discharged following care. However, the survival rate of patients following discharge was low.

Effectiveness of Nerve Blocks for the Management of Head and Neck Cancer Associated Neuropathic Pain Disorders; a Retrospective Study.

Introduction: A portion of patients with head and neck cancer (HNC)- associated pain may not experience relief in symptoms with non-invasive modalities. A nerve block is a procedure in which a local anaesthetic agent is injected along the nerve track to preferentially block sensory transmission. The literature on the effectiveness of nerve blocks in the management of HNC-related pain is limited. The purpose of this study was to determine the effectiveness of nerve blocks in the management of breakthrough HNC-associated trigeminal or cervical neuropathic pain disorders. Materials and Methods: A retrospective chart review of patients who underwent a nerve block or infiltration procedure in the regions of head and neck for the management of breakthrough HNC-associated trigeminal or cervical neuropathic pain disorders in the Orofacial Pain Medicine Clinic, Shaukat Khanum Memorial Cancer Hospital and Research Centre, between November 2018 and November 2019 was completed. Information regarding demographics, diagnosis and pain characteristics was extracted and reviewed. The Fisher's exact test and Mann-Whitney U-test were used for analysis between independent and dependent variables. Results: A total of 27 participants were included in the investigation, of which 66.7% were male. The average pre-procedure pain score was 6.85±2.54. Following intervention, 81.5% of the participants experienced >75% relief in pain for longer than 48 hours. The mean immediate post-procedure pain score was 0.26±1.02 and the average duration of relief was 6.10±6.50 weeks. The significant effect of nerve blocks was found to be statistically associated with the concurrent use of amitriptyline (P = 0.017). Conclusion: Nerve blocks, as an adjunctive therapy to pharmacologic treatment, can provide significant relief to patients with breakthrough HNC-associated trigeminal and cervical neuropathic pain disorders. However, the duration of relief experienced by the participants is inconsistent. The beneficial effect of nerve blocks appears to be more common in patients that were concurrently using amitriptyline.

Clinicopathological Behavior and Treatment-related Outcome of Rare Salivary Duct Carcinoma: The Shaukat Khanum Memorial Cancer Hospital Experience.

Background Salivary gland tumors are rare salivary gland malignancies with resemblance to ductal breast carcinoma. We have described clinicopathological behavior and treatment outcomes of this rare malignancy. Methods Salivary duct carcinoma patients treated from 2010 to 2015 were retrospectively analyzed for clinicopathological characteristics and treatment-related outcomes of the disease. Results A total of 12 patients with salivary duct carcinoma were included in the study. All were males with mean age of 52.58 ± 13.43. Parotid gland was the most commonly involved major salivary gland while buccal mucosa and anterior tongue were most common oral cavity sub-sites involving minor salivary glands. The disease-free survival was 75% at 10 months and 25% at 20 months. The mean follow-up time was 12 months. There were three local recurrences and one distant metastasis. Conclusion Salivary duct carcinoma is a locally aggressive tumor with tendency for local recurrence and distant metastasis. Adverse features such as perineural invasion, extra-capsular spread and advanced nodal disease may worsen prognosis.

An Overview of Laryngeal Cancer Treatment at a Tertiary Care Oncological Center in a Developing Country.

Introduction Development of laryngeal cancer is multifactorial, and management is surrounded with controversies. Recent reports suggest a decline in the survival of these patients. We conducted a study to analyze the clinicopathological parameters and compute the outcomes in terms of survival in patients with laryngeal cancer treated at our institution. Methods Electronic charts of 515 patients with Laryngeal cancer treated at our Hospital and Research Center from 2004 to 2014 were retrospectively reviewed. Results Median age was 62 years. Male: female ratio 91%: 9%. Sixty-two percent were smokers. Histologically, all were squamous cell carcinoma. Most common subsite was glottis (88%). Treatment was non-surgical in 92% and surgical in 8%. The five-year overall survival (OS), disease-specific survival (DSS), disease-free survival (DFS) and locoregional control (LRC) were 67%, 74%, 59% and 70%, respectively. OS, DSS, DFS and LRC for early stage (I-II) and advance stage (III-IV) were 81 and 54%, 86 and 63%, 75 and 45%, and 83 and 57%, respectively. Twenty-two percent recurred locally. Of these failures, 19% were inoperable, 36% were surgically salvaged and 34% refused laryngectomy. Conclusions Our survival rates are comparable with published data. The high refusal rate for salvage total laryngectomy is concerning and needs further study to evaluate the reasons.