Real-world evaluation of nivolumab in patients with non-nasopharyngeal recurrent or metastatic head and neck cancer: a retrospective multi-center study by the Turkish Oncology Group (TOG).

OBJECTIVES: Head and neck cancers (HNCs) represent a significant global health concern due to high morbidity and mortality rates. Despite therapeutic advances, the prognosis for advanced or recurrent cases remains challenging. Nivolumab obtained approval for recurrent or metastatic HNC based on the Phase III CheckMate 141 trial. This study aimed to evaluate the real-world outcomes of nivolumab in patients with non-nasopharyngeal HNC. DESIGN: In this multicenter retrospective study, we analyzed 124 patients with recurrent or metastatic non-nasopharyngeal HNC who received nivolumab in the second-line setting and beyond. Data were collected from 20 different cancer centers across Turkey. The effectiveness and safety of the treatment and survival outcomes were evaluated. RESULTS: Nivolumab exhibited favorable clinical responses, yielding an objective response rate of 29.9% and a disease control rate of 55.7%. Safety assessments revealed a generally well-tolerated profile, with no instances of treatment discontinuation or mortality due to side effects. Survival analysis disclosed a median overall survival (OS) of 11.8 (95% CI 8.4-15.2) months. Multivariate analysis revealed that ECOG-PS ≥ 1 (HR: 1.64, p = 0.045), laryngeal location (HR: 0.531, p = 0.024), and neutrophil-to-lymphocyte ratio > 3.5 (HR: 1.97, p = 0.007) were independent predictors of OS. CONCLUSIONS: Nivolumab is an effective and safe treatment option for patients with recurrent or metastatic non-nasopharyngeal HNC in real-world settings. Further studies are needed on factors affecting response to treatment and survival outcomes.

Evaluation of sarcopenia as a prognostic biomarker in locally advanced head and neck squamous cell carcinoma.

Background: We aimed to evaluate the effect of sarcopenia on survival in head and neck squamous cell carcinoma patients treated with chemoradiotherapy. Materials & methods: Disease-free survival and overall survival were compared according to cervical computed tomography for radiotherapy in 123 sarcopenic and non-sarcopenic patients with locally advanced head and neck squamous cell carcinoma treated with chemoradiotherapy with weekly cisplatin. Results: In multivariate analyses, pretreatment sarcopenia was associated with lower disease-free survival (hazard ratio: 2.60; 95% CI: 1.38-4.87; p = 0.003) and overall survival (hazard ratio: 2.86; 95% CI: 1.40-5.85; p = 0.004). Sarcopenic patients experienced more frequent radiotherapy-related toxicities and platinum-related side effects than non-sarcopenic patients. Conclusion: Sarcopenia could be a potential biomarker to predict prognosis and treatment toxicity in head and neck squamous cell carcinoma.

Head and neck cancer is one of the main causes of cancer-related death worldwide. Most patients are diagnosed in the advanced stage. Muscle wasting with significant weight loss occurs in nearly half of the patients at the initial diagnosis. In oncology research, sarcopenia has often been described as the loss of skeletal muscle mass. In this study, we evaluated the effect of sarcopenia on survival in head and neck cancer patients. Muscle mass was calculated using information from head and neck computed tomography before radiotherapy treatment in patients. We showed that patients with low muscle mass had significantly worse survival rates and were more susceptible to treatment-related side effects. Sarcopenia may function as a marker showing the course of disease in patients with head and neck cancer.

Post-induction lymph node delineation in nasopharyngeal cancer: A single-center experience.

BACKGROUND: We routinely delineate the gross tumor volume (GTV) for the lymph nodes (LN) based on post-induction chemotherapy (IC) MRI in nasopharyngeal carcinoma (NPC). Herein, we investigated the sufficiency of this method, particularly in high-risk LNs. METHODS: Eighty-one LNs with a high-risk of clinical extranodal extension and/or ≥3-cm diameter in 58 patients were evaluated. A new GTV covering the pre-IC LN volume was delineated for each LN. RESULTS: The median volume reduction was 72.5% for the GTV and 53.1% for the planning target volume. After a median 43 months, the overall LN local control rate was 97.5%. The 2- and 5-year LN recurrence-free survival, overall survival, and disease-free survival rate was 88.3% and 84.4%, 92.5% and 85.1%, and 86.8% and 79.2%, respectively. CONCLUSION: IC yields a significant reduction in nodal target volumes, and post-IC nodal volume-based radiotherapy provides excellent LC in NPC, even in high-risk LNs.

The association between pan-immune-inflammation value and survival in head and neck squamous cell carcinoma.

PURPOSE: A significant portion of patients with locally advanced head and neck squamous cell carcinoma (HNSCC) relapse despite multimodality treatment denoting the need for biomarkers. The pan-immune-inflammation value (PIV) is a recently developed blood count-based prognostic biomarker. We evaluated the relationship between PIV and survival in locally advanced HNSCC patients treated with chemoradiotherapy (CRT). METHODS: A total of 199 patients who underwent CRT at Hacettepe University Oncology Hospital were included. The relationship between clinical and laboratory parameters with overall survival (OS) and disease-free survival (DFS) was analyzed by multivariate analyses. RESULTS: The median age was 59 years and 90.5% of the patients were male. 66.8% of the patients had laryngeal primaries, and 78.9% had T3-T4 disease. 84.9% of the patients received CRT with cisplatin. The optimal PIV threshold value was calculated as 404 in ROC analyses. This PIV value had 75.8% sensitivity and 70.4% specificity for OS prediction (AUC 0.781; 95% CI 0.715-0.846; p < 0.001). In multivariate analyses, high PIV levels (≤ 404 vs. > 404, HR 2.862; 95% CI 1.553-5.276; p = 0.001), higher NLR (≤ 2.5 vs. > 2.5, HR 1.827; 95% CI 1.017-3.281; p = 0.044) levels and ECOG performance score of 2 (HR 2.267; 95% CI 1.385-3.711; p = 0.001) were associated with shorter OS. These factors were associated with shorter DFS also (HR for PIV 2.485, 95% CI 1.383-4.467, p = 0.002). CONCLUSIONS: We observed shorter OS and DFS in locally advanced HNSCC patients with high PIV levels. If prospective studies support our findings, the PIV score could be a prognostic biomarker in HNSCC.

Results of concurrent radiotherapy and immunotherapy in recurrent and metastatic head and neck cancer: A single-center experience.

OBJECTIVES: In metastatic and recurrent head and neck cancer (M/R HN-SCC), the median survival is less than a year and locoregional recurrence is the main cause of death. Our aim was to evaluate the results of concurrent stereotactic body radiotherapy (SBRT) and immunotherapy (ICI) in these patients. MATERIALS AND METHODS: Fifteen patients diagnosed with M/R HN-SCC were evaluated retrospectively. All patients received SBRT (3x8 Gy) to all recurrent and metastatic foci with concurrent ICI. RESULTS: Six months overall survival (OS) rates and progression-free survival (PFS) rates were 93% and 86%, respectively. Local control (LC) rate in the site of SBRT was 96%. Higher survival and LC rates were achieved with lower doses of radiotherapy with the synergistic effect of SBRT and ICI. CONCLUSION: Concurrent ICI and SBRT was feasible with excellent LC.

Thyroid gland metastasis mimicking thyroid carcinoma in a lung cancer patient and dramatic response to crizotinib: A case report.

Metastasis of lung adenocarcinoma to the thyroid is extremely rare. Since treatment for primary thyroid cancer and non thyroid malignancy is totally different, precise diagnosis is clinically important.

The Association between the PRECISE-DAPT Score and New-Onset Atrial Fibrillation in Patients with ST-Elevation Myocardial Infarction.

Background: Atrial fibrillation (AF) is associated with increased morbidity in myocardial infarction (MI), especially thromboembolic risk increases. The PRECISE-DAPT (The PREdicting bleeding Complications In patients undergoing Stent implantation and subsEquent Dual Anti-Platelet Therapy) score was created to predict the bleeding risk of dual antiplatelet therapy. The purpose of this study was to evaluate the association between new-onset AF and the PRECISE-DAPT score in ST-segment-elevation myocardial infarction (STEMI). Methods: This retrospective study enrolled patients who developed STEMI within 12 hours of the onset of symptoms and underwent primary percutaneous coronary intervention. The study population was divided into 2 groups of PRECISE-DAPT scores of 25 or greater and PRECISE-DAPT scores of below 25 and their baseline characteristics, as well as laboratory and echocardiography results, were compared. In-hospital new AF and related events were compared between the 2 PRECISE-DAPT score groups. Results: From February 2015 to December 2017, this study enrolled 2234 patients with STEMI at a mean age of 54.4 years. The new-onset AF incidence rate was higher in the higher PRECISE-DAPT group than in the lower PRECISE-DAPT group (62 [28.7 %] vs 58 [2.9%]; P<0.001). According to the multivariate logistic regression analysis, the factors associated with new-onset AF were the left atrial diameter (OR=1.98, 95% confidence interval=1.34-2.93; P=0.001) and the PRECISE-DAPT score (OR=1.04, 95% confidence interval=1.10-1.18; P<0.001). Conclusion: The PRECISE-DAPT score was associated with the development of new-onset AF in our patients with STEMI. Further follow-up of these patients will provide clearer information.

Can Levamisole be used in the treatment of COVID-19 patients presenting with diarrhea?

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was first identified in Wuhan, China, on Jan 7, 2020. Over the following months, the virus rapidly spread throughout the world. Coronavirus Disease 2019 (COVID-19) can involve the gastrointestinal tract, including symptoms like nausea, vomiting and diarrhea and shedding of the SARS-CoV-2 in feces. Angiotensin-converting enzyme 2 (ACE2) protein, which has been proven to be a cell receptor for SARS-CoV-2, is expressed in the glandular cells of gastric, duodenal, and rectal epithelia, supporting the entry of SARS-CoV-2 into the host cells. According to the literature, rates of COVID-19 patients reporting diarrhea were between 7 - 14%. Diarrhea in the course of COVID-19 disease can cause dehydration and hospitalization. Although no antiviral drug was specifically designed for the treatment of diarrhea, several molecules could have beneficial effects by reducing viral replication. In this letter, we discussed the Levamisole, which is an anthelmintic agent with immunomodulatory effects, could be used effectively both for antiviral therapy and especially in COVID-19 patients with diarrhea.

Cancer incidence in Behçet's disease.

BACKGROUND: Previous studies demonstrated an increased cancer risk in autoimmune diseases. Behçet's disease (BD) was also reported to be associated with an increased risk of cancer, although the data is limited. AIMS: In this study, we aimed to assess cancer incidence in a large cohort of BD patients and to compare with the data of the same age and gender groups. METHODS: The study cohort consisted of BD patients of > 18 years of age who were prospectively recorded in the Hacettepe University Vasculitis Center. Data on any cancer was collected from the patient files. Cancer incidence was compared with age- and gender-specific cancer incidence rates of the normal population retrieved from the 2014 Turkish National Cancer Registry (TNCR) data using standardized incidence rates (SIR). RESULTS: Totally, 451 adult cases with BD were included. The median age of the cohort was 43 (20-75), and 52.5% of the patients were males. Eleven cancer cases were observed during a median of 124 months follow-up. Behçet's disease was associated with an increase in cancer risk compared with expected counts in the corresponding age and sex group (SIR 2.84, 95% CI 1.50-4.94, p < 0.001). Patients with papulopustular lesions had a trend toward a decreased risk of cancer (p = 0.060), and patients using azathioprine had a significantly decreased cancer risk (p = 0.031). CONCLUSION: This study revealed BD patients had approximately three times increased cancer risk compared with corresponding age and sex groups. Besides the routine care, increased attention for cancer surveillance is required in the follow-up of BD patients.

Human papillomavirus infection in patients with laryngeal carcinoma.

BACKGROUND: The aim of this study was to determine the HPV positivity rate in patients with laryngeal cancer, and to determine the effect of HPV positivity on survival. An additional aim was to determine if patients with HPV positive laryngeal cancer are more sensitive to chemotherapy and if such sensitivity differs according to chemotherapy protocol. METHODS: The study included laryngeal specimens obtained from 82 laryngeal cancer patients and 11 laryngeal specimens with normal laryngeal mucosa that were obtained from our hospital's paraffin block archives between 1995 and 2013. HPV was detected via chromogenic in situ hybridization (cISH) and confirmed via genotyping. RESULTS: HPV was not detected in any of the 82 laryngeal cancer patients' laryngeal specimens, nor in any of the 11 archived laryngeal specimens with normal laryngeal mucosa via cISH. Genotyping confirmed these findings; none of the HPV types studied were detected in any of the specimens. As none of the study samples were HPV positive, it was not possible to compare survival, recurrence, or chemotherapy sensitivity. CONCLUSIONS: HPV infection is not a leading cause of laryngeal cancer; however, additional research on HPV positivity in patients with laryngeal cancer and its effect on recurrence, survival, and chemotherapy sensitivity is warranted.

The Synergistic Effect of Immune Checkpoint Blockade and Radiotherapy in Recurrent/Metastatic Sinonasal Cancer.

Treatment options for recurrent/metastatic sinonasal cancer (RMSNC) patients are limited. We present two cases with RMSNC treated with a combination of immune checkpoint blockade and hypo-fractionated stereotactic radiotherapy (HSRT).  Case 1 presented with RMSNC three months after the primary treatment. The patient progressed under first-line chemotherapy and pembrolizumab was offered. The disease progressed after the sixth cycle. We performed reirradiation with HSRT to the primary site. Case 2 presented with local recurrence eight years after the primary treatment for maxillary sinus cancer. He refused surgery and chemotherapy and was offered nivolumab treatment. After two doses, we performed reirradiation with HSRT. Case 1 showed regression at both the local and the metastatic sites after radiotherapy. The second patient's symptoms resolved completely three months after radiotherapy. The HSRT and immune checkpoint blockade combination is a promising treatment option for patients with RMSNC.

Modified docetaxel, cisplatin and fluorouracil therapy as the first-line treatment for patients with recurrent/metastatic squamous cell carcinoma of the head and neck cancer: a retrospective study.

AIM: Modified docetaxel, cisplatin, and 5-fluorouracil (mDCF) therapy has been shown to be a well tolerated and highly effective regimen for metastatic gastric carcinoma. Herein we investigated the effectiveness of the mDCF combination as the first-line treatment in patients with recurrent/metastatic squamous cell carcinoma of the head and neck (HNSCC). METHODS: A total of 80 patients with recurrent/metastatic HNSCC who were treated with mDCF between 2009 and 2015 were enrolled into this study. All patients were treated in the first-line with 2-6 cycles of mDCF chemotherapy which consisted of docetaxel 60 mg/m2 intravenously (IV) on day 1, cisplatin 60 mg/m2 IV on day 1, and 5-fluorouracil 600 mg/m2 IV for 5 days of continuous infusion, with cycles repeated every 21 days. RESULTS: The most common grade 3-4 toxicities were neutropenia (22.5%), anemia (10%), thrombocytopenia (7.5%), nephrotoxicity (1.3%), hepatotoxicity (1.3%), and diarrhea (2.5%). Twelve patients (15%) experienced a febrile neutropenic episode. Dose modification was required in 22 (27.5%) of the patients due to drug toxicity. Complete response was achieved in 2.5% of all patients, while partial and stable responses were reported to be 43.8% and 25%, respectively, with a disease control rate of 71.3%. The median progression-free and overall survival was 7 (95% CI: 5.3-8.6) and 11.5 (95% CI: 9.4-13.7) months, respectively. CONCLUSIONS: The efficiency of the mDCF combination for induction chemotherapy has been well established previously. To our knowledge, this is one of the largest studies evaluating the survival and safety significance of mDCF chemotherapy as a first-line treatment in patients with recurrent/metastatic HNSCC.

Detection of O6-methylguanine-DNA methyltransferase gene promoter region methylation pattern using pyrosequencing and the effect of methylation pattern on survival, recurrence, and chemotherapy sensitivity in patients with laryngeal cancer.

AIM: To determine the methylation pattern of the promoter region of the O6-methylguanine-DNA methyltransferase (MGMT) gene in laryngeal cancer and normal laryngeal mucosa samples using pyrosequencing, and to determine the relationship between the methylation pattern of MGMT, and tumor stage, survival, recurrence, and chemosensitivity in patients with laryngeal cancer. MATERIALS AND METHODS: Laryngeal cancer and normal laryngeal mucosa specimens were obtained from our paraffin block archives, and then subjected to pyrosequencing. Different cut-off values were used to detect methylation. Clinicopathological data for the patients that provided specimens were obtained from archive records. RESULTS: When 5% was used as the cut-off value, 78% of the laryngeal cancer specimens (64 of 82), and 27.3% of normal laryngeal mucosa specimens (3 of 11) were considered methylated. When 10% was used as the cut-off value, 47% of the laryngeal cancer specimens (39 of 82), and none of the normal laryngeal mucosa specimens were considered methylated. There was not a significant relationship between the methylation status of MGMT, and clinicopathological parameters, including age, tumor stage, histopathological differentiation, chemoradiotherapy protocol used, recurrence, or disease-free survival. CONCLUSION: Pyrosequencing is a reliable semiquantitative technique that can be used to detect the methylation pattern. Methylation was common in the laryngeal cancer specimens, but there was not a significant relationship between the methylation status of MGMT and clinicopathological parameters.

Renal cell carcinoma metastatic to the tongue: a case report and review of the literature.

Renal cell carcinoma (RCC) metastatic to the head and neck region is quite rare. This report describes a case of RCC metastatic to the oral tongue presenting initially with a renal mass that evaded diagnosis by biopsy examination of the primary lesion and was eventually established as a papillary type RCC by lingual biopsy examination. The tongue mass progressed rapidly despite chemotherapy with interferon-α2b, caused difficulties with oral food intake, and thus necessitated removal by partial glossectomy. Treatment alternatives for lingual RCC metastasis include surgical resection for major functional impairment, risk of airway compromise, or massive hemorrhage. Radiotherapy might be useful and should be considered for specific patients. Lingual metastasis from RCC usually predicts poor survival.

Long-term complications in Hodgkin's lymphoma survivors.

Background. Although patients with Hodgkin's lymphoma (HL) achieve prolonged survival, long-term complications are a major cause of morbidity and mortality among long-term survivors of HL. Methods. We retrospectively evaluated long-term complications in 336 HL survivors treated between January 1990 and January 2006 at the Department of Medical Oncology of the Hacettepe University Institute of Oncology who were >16 years old at presentation. All patients were regularly followed up every 3 months for the first 2 years after complete response, biannually for 3 years, and annually after 5 years. Results. Median follow-up was 8.5 years. The mean age (±SD) of the patients at the time of diagnosis was 35.7 ± 13.1 years. The male to female ratio was 61%/39%. During follow-up, 29 second malignancies (8.6%) were diagnosed in 28 patients with HL; 22 were solid tumors and 7 were hematological malignancies. Forty-seven (14.0%) of all patients with HL were found to have thyroid abnormalities. During follow-up, 54 (16.1%) patients developed cardiovascular complications. Overall, 29 (8.6%) patients developed late pulmonary toxicities. The cumulative number of chronic viral infections was 13 (3.9%). Conclusions. Long-term survivors of HL need to be properly followed up not only for disease control but also for evaluation of possible late morbidities to minimize the consequences.

Ifosfamide and doxorubicin combination chemotherapy for recurrent nasopharyngeal carcinoma patients.

BACKGROUND: We assessed the efficacy and toxicity of ifosfamide and doxorubicin combination chemotherapy (CT) regimen retrospectively in Turkish patients with recurrent or metastatic nasopharyngeal carcinoma (NPC) previously treated with platinum-based chemotherapy. METHODS: A total of thirty patients who had received cisplatin based chemotherapy/chemoradiotherapy as a primary treatment received ifosfamide 2500 mg/m2 days 1-3, mesna 2500 mg/m2 days 1-3, doxorubicin 60 mg/m2 day 1 (IMA), repeated every 21 days. Eligible patients had ECOG PS<2, measurable recurrent or metastatic disease, with adequate renal, hepatic and hematologic functions. RESULTS: Median age was 47 (min-max; 17-60). Twenty six (86.7%) were male. Median cycles of chemotherapy for each patient were 2 (range:1-6). Twenty patients were evaluable for toxicity and response. No patient achieved complete response, with nine partial responses for a response rate of 30.0% in evaluable patients. Stable disease, and disease progression were observed in five (16.7%) and six (20.0%) patients, respectively. Clinical benefit was 46.7%. Median time to progression was 4.0 months. Six patients had neutropenic fever after IMA regimen and there were one treatment-related death due to tumor lysis syndrome in first cycle of the CT. No cardiotoxicity was observed after CT and treatments were generally well tolerated. CONCLUSION: Ifosfomide and doxorubicin combination is an effective regimen for patients with recurrent and metastatic NPC. For NPC patients demonstrating failure of cisplatin based regimens, this CT combination may be considered as salvage therapy.

A retrospective comparison of robotic stereotactic body radiotherapy and three-dimensional conformal radiotherapy for the reirradiation of locally recurrent nasopharyngeal carcinoma.

PURPOSE: We assessed therapeutic outcomes of reirradiation with robotic stereotactic radiotherapy (SBRT) for locally recurrent nasopharyngeal carcinoma (LRNPC) patients and compared those results with three-dimensional conformal radiotherapy (CRT) with or without brachytherapy (BRT). METHODS AND MATERIALS: Treatment outcomes were evaluated retrospectively in 51 LRNPC patients receiving either robotic SBRT (24 patients) or CRT with or without BRT (27 patients) in our department. CRT was delivered with a 6-MV linear accelerator, and a median total reirradiation dose of 57 Gy in 2 Gy/day was given. Robotic SBRT was delivered with CyberKnife (Accuray, Sunnyvale, CA). Patients in the SBRT arm received 30 Gy over 5 consecutive days. We calculated actuarial local control and cancer-specific survival rates for the comparison of treatment outcomes in SBRT and CRT arms. The Common Terminology Criteria for Adverse Events v3.0 was used for toxicity evaluation. RESULTS: The median follow-up was 24 months for all patients. Two-year actuarial local control rates were 82% and 80% for SBRT and CRT arms, respectively (p = 0.6). Two-year cancer-specific survival rates were 64% and 47% for the SBRT and CRT arms, respectively (p = 0.4). Serious late toxicities (Grade 3 and above) were observed in 21% of patients in the SBRT arm, whereas 48% of patients had serious toxicity in the CRT arm (p = 0.04). Fatal complications occurred in three patients (12.5%) of the SBRT arm, and four patients (14.8%) of the CRT arm (p = 0.8). T stage at recurrence was the only independent predictor for local control and survival. CONCLUSION: Our robotic SBRT protocol seems to be feasible and less toxic in terms of late effects compared with CRT arm for the reirradiation of LRNPC patients.