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Introduction: Advanced oral carcinoma surgery results in large denuded areas leading to seroma and hematoma. Closed suction drains obliterate dead space and create negative pressure on wound bed. Non-placement or early removal of drain can lead to various complications, while placement for long duration can cause surgical site infection. The study aims to evaluate factors affecting postoperative neck drain volume, guiding surgeons for decision making for time of drain removal. Methods: The study comprised of 222 patients with oral squamous cell carcinoma who underwent primary tumor resection and neck dissection. Demographical, clinical, and surgical details were retrospectively analyzed. Results: The mean age of patients was 49.1 years. Majority of patients had advanced disease requiring extensive surgery. Patients with radical neck dissection and those reconstructed with pedicled flap had statistically significant drain volume as compared to those with selective neck dissection and free flaps, respectively. Patients with longer duration of surgery, higher blood loss, low postoperative albumin value, and complications showed increased drain volume. Mean duration of drain removal was 7 days, and all drains were removed by day 10. Discussion: Advanced stage primary disease, radical and modified neck dissections, PMMC flap reconstruction, longer duration of surgery, and higher blood loss had higher drain output. Thus, patient parameters, tumor factors, and surgery factors influence drain output and hospitalization. Conclusion: Diligent preoperative and perioperative assessment of various factors can aid trainee surgeons to make decisions for appropriate time for drain removal.
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Introduction: Early retromolar trigone (RMT) lesions are difficult to access and free tissue transfer is often an overkill for such small lesions. The aim was to devise a novel surgical approach that would aid the resection without raising a cheek flap and simultaneously provide a local reconstructive option for small lesions in the RMT. Methodology: This study was to demonstrate the outcomes of the "trans-facial" approach used to simultaneously access and reconstruct small RMT tumors through an islanded nasolabial flap. Patients with histologically proven squamous cell carcinoma of RMT requiring surgery were included from January 2021 to September 2022. Case selection was done based on the location of the disease and its size (cT1/T2). All needed bone and soft tissue resection via per oral trans-facial approach, along with an ipsilateral neck dissection. The technique is described along with their post-operative and pathologic outcomes. Results: Out of the eight patients included in this study, six underwent a bi-alveolar marginal resection and reconstructed using the trans-facial approach. No major complications were noted in the post-operative period. 50% were pT1 tumors and 75% were pN0 status. One patient had a close margin; while, the others had adequate resection margins. All patients were followed up for a median of 18 months with a locoregionally controlled status. Conclusion: The trans-facial approach can be a suitable option with a reasonable oncologic outcome to address small RMT lesions.
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BACKGROUND: Resection of oral cavity carcinoma often leads to complex defects causing functional and aesthetic morbidity. Providing optimum reconstruction with free flaps becomes challenging in a high-volume center setting with constrained resources. Hence, understanding the local flap technique for reconstructing oral cancer defects is prudent. MATERIALS AND METHODS: This study is a retrospective analysis of prospectively operated cases of oral cavity resections which were subsequently reconstructed using local flaps from 2019 to 2022. Patients who underwent reconstruction with either melolabial flap, islanded facial artery myomucosal (FAMM) flap, submental flap, supraclavicular artery island flap, infrahyoid flap, or platysma myocutaneous flap (PMF) were included in this analysis. Eligible patients were followed up to evaluate functional outcomes like oral feeding and to analyze the Performance Status Scale for Head and Neck Cancer. RESULTS: The study included 104 patients. The tongue was the most common subsite, resulting in most hemiglossectomy defects, which were reconstructed using the melolabial flap procedure. Buccal mucosa defects in our series were reconstructed using the supraclavicular flap, whereas the submental flap procedure was the choice for lower lip-commissure defects. Complications such as partial and total flap loss, deep neck infection, and donor site complications like infection and gaping, oral cutaneous fistula, parotid fistula, and seroma were analyzed; the supraclavicular flap presented with a majority of complications. CONCLUSION: Local flaps are an alternative to free flap reconstruction in select cases with optimum functional outcomes and minimal donor site morbidity. This article comprehensively reviews the surgical steps for various local flap procedures in oral cancer defects.
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Introduction: Surgical site infections (SSIs) are a substantial healthcare burden in low- and middle- income countries. "Clean Cut" is a checklist-based infection prevention and control (IPC) program intended to improve compliance to peri-operative IPC standards. We aim to study the short-term and long-term impact of its implementation in a tertiary care cancer referral center. Methods: This was a single institute, prospective interventional study. Patients undergoing elective head-neck surgical procedures were included. The "Clean Cut" program consisting of surveillance, audits, and IPC training was implemented for 6 months, after which there was no active oversight. Post-intervention (T2) and 1-year follow-up (T3) data regarding compliance to core IPC practices and SSI rates were compared with baseline (T1). Results: One hundred eighty six patients were included with 50 (26.9%), 86 (46.2%), and 50 (26.9%) patients at T1, T2, and T3, respectively. At baseline, teams complied with a mean of 3.56 of the six critical components of infection control processes which rose to 4.66 (p < 0.001) at T2, but decreased to 4.02 at T3 (p = 0.053). The SSI rate at baseline decreased significantly after Clean Cut implementation [16 (32%) vs. 12 (13.95%), p = 0.012], but returned to baseline levels after 1 year [17 (34%), p = 0.006]. Conclusion: Implementation of the "Clean Cut" program increases compliance to infection control processes and reduces SSI rates in the short term. Without continuing oversight, these rates return to baseline values after 1 year.
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Controle de Infecções , Melhoria de Qualidade , Infecção da Ferida Cirúrgica , Humanos , Índia , Infecção da Ferida Cirúrgica/prevenção & controle , Infecção da Ferida Cirúrgica/epidemiologia , Estudos Prospectivos , Masculino , Feminino , Controle de Infecções/métodos , Controle de Infecções/normas , Pessoa de Meia-Idade , Lista de Checagem , Adulto , Idoso , Centros de Atenção Terciária/estatística & dados numéricos , Fidelidade a Diretrizes/estatística & dados numéricos , Assistência Perioperatória/normas , Assistência Perioperatória/métodosRESUMO
OBJECTIVE: The 2x2 factorial design is an effective method that allows for multiple comparisons, especially in the context of interactions between different interventions, without substantially increasing the required sample size. In view of the considerable preclinical evidence for Curcumin and Metformin in preventing the development and progression of head and neck squamous cell carcinoma (HNSCC), this study describes the protocol of the clinical trial towards applying the drug combination in prevention of second primary tumors. METHODS: We have applied the trial design to a large phase IIB/III double-blind, multi-centric, placebo-controlled, randomized clinical trial to determine the safety and efficacy of Metformin and Curcumin in the prevention of second primary tumours (SPT) of the aerodigestive tract following treatment of HNSCC (n=1,500) [Clinical Registry of India, CTRI/2018/03/012274]. Patients recruited in this trial will receive Metformin (with placebo), Curcumin (with placebo), Metformin, and Curcumin or placebo alone for a period of 36 months. The primary endpoint of this trial is the development of SPT, while the secondary endpoints are toxicities associated with the agents, incidence of recurrence, and identifying potential biomarkers. In this article, we discuss the 2x2 factorial design and how it applies to the head and neck cancer chemoprevention trial. CONCLUSION: 2x2 factorial design is an effective trial design for chemoprevention clinical trials where the effectiveness of multiple interventions needs to be tested parallelly.
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Curcumina , Neoplasias de Cabeça e Pescoço , Metformina , Segunda Neoplasia Primária , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Curcumina/uso terapêutico , Método Duplo-Cego , Seguimentos , Neoplasias de Cabeça e Pescoço/prevenção & controle , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Metformina/uso terapêutico , Segunda Neoplasia Primária/prevenção & controle , Prognóstico , Ensaios Clínicos Controlados Aleatórios como Assunto , Projetos de Pesquisa , Carcinoma de Células Escamosas de Cabeça e Pescoço/prevenção & controle , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Ensaios Clínicos Fase II como Assunto , Estudos Multicêntricos como Assunto , Ensaios Clínicos Fase III como AssuntoRESUMO
BACKGROUND: Adenoid cystic carcinoma (ACC) is a rare and malignant tumor of the salivary glands. Despite its slow-growing nature, this clinical entity is notorious for presenting with distant metastasis (DM) which significantly worsens patient outcomes. The role of surgery in patients with ACC and distant metastasis (DM) remains controversial. METHODS: We conducted a retrospective analysis of 47 patients with ACC who underwent surgery for the primary tumor and presented with DM at baseline or developed DM during follow-up. We compared survival outcomes between patients with DM at baseline (Group A) and those who developed DM during follow-up (Group B). RESULTS: The median overall survival (OS) for the entire cohort was 88%. Patients with DM at baseline (Group A) had significantly worse OS (51%) compared to those without DM at baseline (Group B) (91%; P = .04). Local recurrence (LR) was associated with poor survival in both groups. However, salvage surgery for LR+DM was associated with improved OS compared to palliative treatment (100% vs 77%; P = .79). CONCLUSION: Our findings suggest that surgery for the primary tumor of ACC may provide survival benefits in patients with DM. Salvage surgery should be considered particularly for patients who develop local recurrence and distant metastasis during follow-up.
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Carcinoma Adenoide Cístico , Recidiva Local de Neoplasia , Humanos , Carcinoma Adenoide Cístico/cirurgia , Carcinoma Adenoide Cístico/patologia , Carcinoma Adenoide Cístico/secundário , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Idoso , Adulto , Recidiva Local de Neoplasia/patologia , Neoplasias das Glândulas Salivares/patologia , Neoplasias das Glândulas Salivares/cirurgia , Metástase Neoplásica , Neoplasias de Cabeça e Pescoço/cirurgia , Neoplasias de Cabeça e Pescoço/patologia , Terapia de Salvação , Resultado do Tratamento , Taxa de Sobrevida , Idoso de 80 Anos ou maisRESUMO
AIM OF THE STUDY: We previously reported a survival benefit of elective neck dissection (END) over therapeutic neck dissection (TND) in patients with clinically node-negative early-stage oral cancer. We now report the results of the second question in the same study addressing the impact of adding neck ultrasound to physical examination during follow-up on outcomes. METHODS: Patients with lateralized T1/T2 oral squamous cell carcinoma (SCC) were randomized to END or TND and to follow-up with physical-examination plus neck ultrasound (PE+US) versus physical-examination (PE). The primary endpoint was overall survival (OS). RESULTS: Between January 2004 and June 2014, 596 patients were enrolled. This is an intention to treat analysis of 592 analysable patients, of whom 295 were allocated to PE+US and 297 to PE with a median follow-up of 77.47 months (interquartile range (IQR) 54.51-126.48). There was no significant difference (unadjusted hazard ratio [HR], 0.92, 95% CI, 0.71-1.20, p = 0.54) in 5-year OS between PE+US (70.8%, 95% CI, 65.51-76.09) and PE (67.3%, 95% CI, 61.81-72.79). Among 131 patients with neck node relapse as the first event, the median time to relapse detection was 4.85 (IQR 2.33-9.60) and 7.62 (IQR 3.22-9.86) months in PE+US and PE arms, respectively. The N stage in the PE+US arm was N1 33.8%, N2a 7.4%, N2b/c 44.1% and N3 14.7% while in PE was N1 28.6%, N2a 9.5%, N2b/c 39.7%, N3 20.6% and unknown 1.6%. CONCLUSION: Adding neck ultrasound to physical examination during follow-up detects nodal relapses earlier but does not improve overall survival.
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Carcinoma de Células Escamosas , Neoplasias Bucais , Esvaziamento Cervical , Exame Físico , Ultrassonografia , Humanos , Masculino , Feminino , Neoplasias Bucais/patologia , Neoplasias Bucais/mortalidade , Neoplasias Bucais/diagnóstico por imagem , Neoplasias Bucais/terapia , Neoplasias Bucais/cirurgia , Pessoa de Meia-Idade , Ultrassonografia/métodos , Idoso , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/diagnóstico por imagem , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/terapia , Estadiamento de Neoplasias , Seguimentos , Resultado do TratamentoRESUMO
INTRODUCTION: India contributes two-thirds of the global mortality due to oral cancer and has a younger population at risk. The societal costs of this premature mortality are barely discussed. METHODS: Using the human capital approach, we aimed to estimate the productivity lost due to premature mortality, valued using individual socioeconomic data, related to oral cancer in India. A bottom-up approach was used to prospectively collect data of 100 consecutive patients with oral cancer treated between 2019 and 2020, with a follow-up of 36 months. RESULTS: The disease-specific survival for early and advanced stage was 85% and 70%, with a median age of 47 years. With 671 years lost prematurely, the loss of productivity was $41 900/early and $96 044/advanced stage. Based on population level rates, the total cost of premature mortality was $5.6 billion, representing 0.18% of GDP. CONCLUSION: India needs to implement tailored strategies to reduce the economic burden from premature mortality.
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Eficiência , Mortalidade Prematura , Neoplasias Bucais , Humanos , Índia , Masculino , Pessoa de Meia-Idade , Feminino , Estudos Prospectivos , Neoplasias Bucais/mortalidade , Neoplasias Bucais/economia , Adulto , Efeitos Psicossociais da Doença , IdosoRESUMO
The Head and Neck Cancer International Group (HNCIG) has undertaken an international modified Delphi process to reach consensus on the essential data variables to be included in a minimum database for HNC research. Endorsed by 19 research organisations representing 34 countries, these recommendations provide the framework to facilitate and harmonise data collection and sharing for HNC research. These variables have also been incorporated into a ready to use downloadable HNCIG minimum database, available from the HNCIG website.
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Ensaios Clínicos como Assunto , Consenso , Bases de Dados Factuais , Neoplasias de Cabeça e Pescoço , Humanos , Neoplasias de Cabeça e Pescoço/terapia , Bases de Dados Factuais/normas , Ensaios Clínicos como Assunto/normas , Técnica Delphi , Pesquisa Biomédica/normasRESUMO
Head and neck cancer is a major cause of morbidity and mortality worldwide. The identification of genetic alterations in head and neck cancer may improve diagnosis and treatment outcomes. In this study, we report the identification and functional characterization of UBE3C-LRP5 translocation in head and neck cancer. Our whole transcriptome sequencing and RT-PCR analysis of 151 head and neck cancer tumor samples identified the LRP5-UBE3C and UBE3C-LRP5 fusion transcripts in 5.3% of patients of Indian origin (n = 151), and UBE3C-LRP5 fusion transcripts in 1.2% of TCGA-HNSC patients (n = 502). Further, whole genome sequencing identified the breakpoint of UBE3C-LRP5 translocation. We demonstrate that UBE3C-LRP5 fusion is activating in vitro and in vivo, and promotes the proliferation, migration, and invasion of head and neck cancer cells. In contrast, depletion of UBE3C-LRP5 fusion suppresses the clonogenic, migratory, and invasive potential of the cells. The UBE3C-LRP5 fusion activates the Wnt/ß-catenin signaling by promoting nuclear accumulation of ß-catenin, leading to upregulation of Wnt/ß-catenin target genes, MYC, CCND1, TCF4, and LEF1. Consistently, treatment with the FDA-approved drug, pyrvinium pamoate, significantly reduced the transforming ability of cells expressing the fusion protein and improved survival in mice bearing tumors of fusion-overexpressing cells. Interestingly, fusion-expressing cells upon knockdown of CTNNB1, or LEF1 show reduced proliferation, clonogenic abilities, and reduced sensitivity to pyrvinium pamoate. Overall, our study suggests that the UBE3C-LRP5 fusion is a promising therapeutic target for head and neck cancer and that pyrvinium pamoate may be a potential drug candidate for treating head and neck cancer harboring this translocation.
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BACKGROUND: Advanced head and neck cancers are known to cause swallowing dysfunction due to anatomical and post-treatment changes. Literature is sparse on post-surgical and/or multi-modality therapy-associated swallowing function in advanced oral cancers. We conducted this study to longitudinally assess and compare the pre- and post-therapy swallowing dysfunction associated with locally advanced oral cancers. METHODS AND MATERIAL: A prospective observational longitudinal study was conducted at a tertiary cancer center from 2017 to 2018 including treatment-naive cT4a oral cancer patients (AJCC 7th edition). The assessment was done pre-surgery, post-surgery, and post-adjuvant setting as per the scales (Dysphagia score, Penetration aspiration scale, and Yale pharyngeal residue (vallecular and pyriform fossa). RESULTS: Of the 30 patients in the study, 47.4%, 47.4%, 52.6%, and 47.4% experienced deterioration of Dysphagia score, Penetration-Aspiration Scale (PAS), vallecula residue, and pyriform residue scores in the postoperative period. And 52.6%, 47.4%, 68.4%, and 57.9% had inferior dysphagia score, PAS, vallecula, and pyriform residue scores even 6 months after completion of adjuvant therapy. The dysphagia score correlated well with other objective assessment scores at different time points. CONCLUSION: Swallowing functions are significantly affected by surgery and adjuvant therapy and continue to be affected even 6 months after completion of treatment. Appropriate rehabilitation and intervention must be offered to patients to reduce this problem. Dysphagia scores can predict the swallowing status similar to other objective assessments.
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Transtornos de Deglutição , Neoplasias Bucais , Humanos , Deglutição , Transtornos de Deglutição/etiologia , Estudos Longitudinais , Estudos Prospectivos , Neoplasias Bucais/complicações , Neoplasias Bucais/cirurgiaRESUMO
BACKGROUND: Neoadjuvant chemotherapy (NACT) with TPF (docetaxel, cisplatin, and 5FU) is one of the treatment options in very locally advanced oral cancer with a survival advantage over PF (cisplatin and 5FU). TP (docetaxel and cisplatin) has shown promising results with a lower rate of adverse events but has never been compared to TPF. METHODS: In this phase 3 randomized superiority study, adult patients with borderline resectable locally advanced oral cancers were randomized in a 1:1 fashion to either TP or TPF. After the administration of 2 cycles, patients were evaluated in a multidisciplinary clinic and further treatment was planned. The primary endpoint was overall survival (OS) and secondary endpoints were progression-free survival (PFS) and adverse events. RESULTS: 495 patients were randomized in this study, 248 patients in TP arm and 247 in TPF arm. The 5-year OS was 18.5% (95% CI 13.8-23.7) and 23.9% (95% CI 18.1-30.1) in TP and TPF arms, respectively (Hazard ratio 0.778; 95% CI 0.637-0.952; P = 0.015). Following NACT, 43.8% were deemed resectable, but 34.5% underwent surgery. The 5-year OS was 50.7% (95% CI 41.5-59.1) and 5% (95%CI 2.9-8.1), respectively, in the surgically resected versus unresected cohort post NACT (P < 0.0001). Grade 3 or above adverse events were seen in 97 (39.1%) and 179 (72.5%) patients in the TP and TPF arms, respectively (P < 0.0001). CONCLUSION: NACT with TPF has a survival benefit over TP in borderline resectable oral cancers, with an increase in toxicity which is manageable. Patients who undergo surgery achieve a relatively good, sustained survival.
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Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Adulto , Humanos , Docetaxel/uso terapêutico , Platina/uso terapêutico , Cisplatino , Terapia Neoadjuvante , Fluoruracila , Taxoides/uso terapêutico , Carcinoma de Células Escamosas/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias Bucais/tratamento farmacológico , Neoplasias Bucais/cirurgia , Quimioterapia de Indução/métodos , Neoplasias de Cabeça e Pescoço/tratamento farmacológicoRESUMO
BACKGROUND: Translationally controlled tumour protein (TCTP) is a multifunctional protein elevated in multiple cancers. However, studies on its role in oral carcinogenesis and prognosis are rare. We recently reported the role of its interacting partner, MCL1, in oral cancer progression and outcome. Hence, the present study aimed to assess TCTP expression in oral tumorigenesis and its association with patient outcomes alone and in combination with MCL1. METHODS: TCTP expression was assessed by immunohistochemistry and immunoblotting in oral tissues and cells, respectively. Cell viability post siRNA/dihydroartemisinin treatment was analysed by tetrazolium salt assay. Cell survival, invasion and tumorigenic potential post TCTP knockdown were assessed by clonogenic, Matrigel and soft-agar assays, respectively. The association of TCTP with patient outcome was analysed by Kaplan-Meier and Cox regression. RESULTS: TCTP was significantly overexpressed in oral premalignant lesions (p < 0.0001), oral tumours (p < 0.0001) and oral dysplastic and cancer cells versus normal oral mucosa and also in recurrent (p < 0.05) versus non-recurrent oral tumours. Further, elevated TCTP was significantly (p < 0.05) associated with poor recurrence free survival (RFS) and poor overall survival (OS; hazard ratio = 2.29; p < 0.05). Intriguingly, the high co-expression of TCTP and MCL1 further reduced the RFS (p < 0.05) and OS (p < 0.05; hazard-ratio = 3.49; p < 0.05). Additionally, TCTP knockdown decreased survival (p < 0.05), invasion (p < 0.01) and in vitro tumorigenic potential (p < 0.0001). Dihydroartemisinin treatment reduced TCTP levels and viability of oral cancer cells. CONCLUSION: Our studies demonstrate an oncogenic role of TCTP in oral cancer progression and poor outcome. Thus, TCTP may be a potential prognostic marker and therapeutic target in oral cancers.
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Artemisininas , Neoplasias Bucais , Humanos , Artemisininas/farmacologia , Artemisininas/uso terapêutico , Biomarcadores Tumorais/metabolismo , Neoplasias Bucais/genética , Proteína de Sequência 1 de Leucemia de Células Mieloides , Proteína Tumoral 1 Controlada por TraduçãoRESUMO
We have conducted this study to understand the impact of poor differentiation (PD), as a sole poor prognostic factor, in early oral cancers. This was a retrospective analysis of a prospectively maintained database of clinically node-negative early T stage OSCC patients operated between 2012 and 2014. Impact of PD on the survival and role of adjuvant therapy in these patients was noted. Out of 1172 patients screened, 280 patients were found to be eligible for the study. 11.4% patients had PDSCC. It was found to be associated with tongue cancers and peri-neural invasion. It had a significant impact on OS and DFS (48.7 months vs 81.4 months, p < 0.00 and 44.6 months vs 73.5 months, p < 0.00 respectively. Hazard ratio for DFS: 4.08. Although patients with PDSCC had better survival with radiotherapy, but this was not statistically significant. Poor differentiation as a stand-alone factor impacts survival in patients with early oral cancer. It may be seen more often in patients with tongue cancer and may have associated PNI. The role of adjuvant therapy in such patients is not clear.
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BACKGROUND: To assess the efficacy of prophylactic versus reactive feeding strategy in oral cavity squamous cell carcinoma (OCSCC) patients receiving adjuvant radiation therapy (RT). METHODS: This was a post hoc analysis of patients of OCSCC enrolled in a randomized trial comparing three adjuvant strategies. In this trial, till 2010, a prophylactic feeding approach was followed for all patients. Since January 2011, a reactive feeding approach was followed. RESULTS: Two hundred and sixty-eight in each cohort (total n = 526) were eligible for analysis after propensity score matching. At 6 weeks post-RT completion, the median weight loss in the prophylactic versus reactive cohort was 5 versus 3 kg, p = 0.002. At all other time points until 1 year, the median weight loss was lesser in reactive than in the prophylactic cohort. CONCLUSIONS: A reactive feeding tube approach should be preferred for OCSCC receiving adjuvant RT.
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Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Humanos , Carcinoma de Células Escamosas/patologia , Gastrostomia , Análise por Pareamento , Neoplasias Bucais/patologia , Pontuação de Propensão , Radioterapia Adjuvante , Estudos Retrospectivos , Carcinoma de Células Escamosas de Cabeça e Pescoço , Redução de PesoRESUMO
OBJECTIVE: To assess the diagnostic performance of response assessment 18F-fluorodeoxyglucose positron emission tomography/contrast-enhanced computed tomography (FDG-PET/CECT) following definitive radio(chemo)therapy in head and neck squamous cell carcinoma (HNSCC) using Neck Imaging Reporting and Data System (NI-RADS). STUDY DESIGN: A retrospective analysis from a prospectively maintained dataset. SETTING: Tertiary-care comprehensive cancer center in a low-middle-income country. METHODS: Adults with newly diagnosed, biopsy-proven, nonmetastatic HNSCC treated with definitive radio(chemo)therapy were included. Posttreatment response assessment FDG-PET/CECT scans were retrospectively assigned NI-RADS categories (1-3) for the primary site, neck, and both sites combined. Locoregional recurrence occurring within 2-years was defined as the event of interest. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and overall accuracy were calculated. Locoregional control stratified by NI-RADS categories was computed with the Kaplan-Meier method and compared using the log-rank test. RESULTS: Posttreatment FDG-PET/CECT scans were available in 190 patients constituting the present study cohort. Sensitivity, specificity, PPV, NPV, and overall accuracy of the NI-RADS template for the primary site was 73.5%, 81.4%, 46.3%, 93.4%, and 80.0%, respectively. Similar metrics for the neck were 72.7%, 87.5%, 43.2%, 96.1%, and 85.8%, respectively. Combining primary site and neck, the corresponding metrics of diagnostic accuracy were 84.4%, 69.7%, 46.3%, 93.5%, and 73.2%, respectively. At a median follow-up of 40 months, Kaplan-Meier estimates of 2-year locoregional control were significantly higher for NI-RADS category 1 (94.2%) compared to NI-RADS category 2 (69.4%) and category 3 (20.4%), respectively (stratified log-rank p < .0001). CONCLUSION: FDG-PET/CECT using the NI-RADS template is associated with good diagnostic performance and prognostic utility in HNSCC treated with definitive radio(chemo)therapy.
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Fluordesoxiglucose F18 , Neoplasias de Cabeça e Pescoço , Adulto , Humanos , Carcinoma de Células Escamosas de Cabeça e Pescoço/diagnóstico por imagem , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia , Estudos Retrospectivos , Neoplasias de Cabeça e Pescoço/diagnóstico por imagem , Neoplasias de Cabeça e Pescoço/terapia , Recidiva Local de Neoplasia/diagnóstico por imagem , Recidiva Local de Neoplasia/terapia , Tomografia por Emissão de Pósitrons/métodos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Compostos RadiofarmacêuticosRESUMO
BACKGROUND: Limited data exists regarding the impact of intensification of adjuvant therapy in resected Oral Cavity Squamous Cell Carcinomas (OCSCC) with adverse prognostic features on histopathology. PATIENTS AND METHODS: This was a three-arm phase III, randomised trial including patients with resected advanced OCSCC. Randomisation was done in a 1:1:1 ratio: Arm-A- standard adjuvant radiation therapy (RT) 60Gy/30 fractions over 6 weeks versus Arm-B-concurrent chemoradiation versus Arm-C-accelerated radiation therapy (6 d a week). The trial was powered to detect an absolute difference of 10% in 5-year Locoregional Control (LRC). RESULTS: The trial was conducted between June 2005 and March 2013. Majority of the patients were males, had T3-T4 disease, had N2-N3 nodal status and had Extra-Capsular Extension (ECE) in nodes. The median follow-up was 95.9 months. There was no difference between the three arms (A versus B versus C) for 10-year locoregional control (LRC): 60.2% versus 61.4% versus 65.7%, p = 0.57; disease free survival (DFS): 37.4% versus 43.9% versus 39.6%, p = 0.40; or Overall Survival (OS): 39.7% versus 46.6% versus 40.4%, p = 0.40. There was no benefit of intensification with either modality in patients with any single adverse pathological factor. A benefit of intensification could be seen in patients with a combination of high-risk features: T3-T4 primary tumours with N2-N3 nodes along with ECE for DFS (Arm B versus Arm A HR) = 0.53, Arm C versus Arm A HR = 0.63) and OS (Arm B versus Arm A HR = 0.58, Arm C versus Arm A HR = 0.60). CONCLUSIONS: All optimally resected OCSCC with adverse features did not benefit from intensification of adjuvant therapy. Only a cohort of patients with a combination of high-risk features are likely candidates for intensification. CLINICAL TRIAL REGISTRATION: NCT00193843.
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Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Masculino , Humanos , Feminino , Carcinoma de Células Escamosas/cirurgia , Terapia Combinada , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia , Neoplasias Bucais/cirurgia , Neoplasias Bucais/patologia , Tomografia Computadorizada por Raios XRESUMO
Occult lymph-node metastasis is a crucial predictor of tongue cancer mortality, with an unmet need to understand the underlying mechanism. Our immunohistochemical and real-time PCR analysis of 208 tongue tumors show overexpression of Matrix Metalloproteinase, MMP10, in 86% of node-positive tongue tumors (n = 79; p < 0.00001). Additionally, global profiling for non-coding RNAs associated with node-positive tumors reveals that of the 11 significantly de-regulated miRNAs, miR-944 negatively regulates MMP10 by targeting its 3'-UTR. We demonstrate that proliferation, migration, and invasion of tongue cancer cells are suppressed by MMP10 knockdown or miR-944 overexpression. Further, we show that depletion of MMP10 prevents nodal metastases using an orthotopic tongue cancer mice model. In contrast, overexpression of MMP10 leads to opposite effects upregulating epithelial-mesenchymal-transition, mediated by a tyrosine kinase gene, AXL, to promote nodal and distant metastasis in vivo. Strikingly, AXL expression is essential and sufficient to mediate the functional consequence of MMP10 overexpression. Consistent with our findings, TCGA-HNSC data suggests overexpression of MMP10 or AXL positively correlates with poor survival of the patients. In conclusion, our results establish that the miR-944/MMP10/AXL- axis underlies lymph node metastases with potential therapeutic intervention and prediction of nodal metastases in tongue cancer patients.
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Receptor Tirosina Quinase Axl , Metaloproteinase 10 da Matriz , MicroRNAs , Neoplasias da Língua , Animais , Camundongos , Metástase Linfática , Metaloproteinase 10 da Matriz/genética , MicroRNAs/genética , Neoplasias da Língua/genética , Neoplasias da Língua/patologia , Receptor Tirosina Quinase Axl/genéticaRESUMO
PURPOSE: There is a lack of published literature on systemic therapeutic options in cisplatin-ineligible patients with locally advanced head and neck squamous cell carcinoma (LAHNSCC) undergoing chemoradiation. Docetaxel was assessed as a radiosensitizer in this situation. METHODS: This was a randomized phase II/III study. Adult patients (age ≥ 18 years) with LAHNSCC planned for chemoradiation and an Eastern Cooperative Oncology Group performance status of 0-2 and who were cisplatin-ineligible were randomly assigned in 1:1 to either radiation alone or radiation with concurrent docetaxel 15 mg/m2 once weekly for a maximum of seven cycles. The primary end point was 2-year disease-free survival (DFS). RESULTS: The study recruited 356 patients between July 2017 and May 2021. The 2-year DFS was 30.3% (95% CI, 23.6 to 37.4) versus 42% (95% CI, 34.6 to 49.2) in the RT and Docetaxel-RT arms, respectively (hazard ratio, 0.673; 95% CI, 0.521 to 0.868; P value = .002). The corresponding median overall survival (OS) was 15.3 months (95% CI, 13.1 to 22.0) and 25.5 months (95% CI, 17.6 to 32.5), respectively (log-rank P value = .035). The 2-year OS was 41.7% (95% CI, 34.1 to 49.1) versus 50.8% (95% CI, 43.1 to 58.1) in the RT and Docetaxel-RT arms, respectively (hazard ratio, 0.747; 95% CI, 0.569 to 0.980; P value = .035). There was a higher incidence of grade 3 or above mucositis (22.2% v 49.7%; P < .001), odynophagia (33.5% v 52.5%; P < .001), and dysphagia (33% v 49.7%; P = .002) with the addition of docetaxel. CONCLUSION: The addition of docetaxel to radiation improved DFS and OS in cisplatin-ineligible patients with LAHNSCC.[Media: see text].
Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Adulto , Humanos , Adolescente , Docetaxel/uso terapêutico , Cisplatino/uso terapêutico , Carcinoma de Células Escamosas/tratamento farmacológico , Taxoides/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológicoRESUMO
Context: The submandibular glands (SMGs) excision during head-and-neck oncosurgeries lead to significant morbidity and degradation of quality of life (QOL). The preservation of SMGs during head-and-neck oncosurgeries, without affecting oncological safety, will improve QOL by preventing xerostomia in these patients. Aims: The aim of this retrospective study was to assess the involvement of SMG by malignancy during neck dissection being done for the squamous cell carcinoma (SCC) of tongue and to evaluate oncological safety of SMG preservation in SCC of the tongue. Settings and Design: The study design was a retrospective analytical study. Subjects and Methods: The study included 391 patients of SCC of tongue operated at Quaternary oncological center from January 2016 to February 2020. The treatment records of 371 patients were reviewed for demographical data, nodal metastasis, and histopathological involvement of SMG by SCC. The statistical analysis was done using SPSS 22. Results: A total of 555 necks dissected were assessed, out of which 95 necks dissected were positive for nodal metastasis at level Ib. The SMG was involved by SCC in only two cases, both of which were poorly differentiated SCC. No intraglandular lymph nodes were detected in any of the SMG dissected. Conclusions: The study showed that involvement of the SMG by SCC of the tongue is not very common, and it may be possible to preserve the SMG during neck dissection in selected cases in SCC of the tongue. The preservation will definitely improve QOL of the patients, as excision of the SMG is one of the prominent factors, resulting in xerostomia.