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Background: In view of improving biomarkers predicting the efficacy of immunotherapy for head and neck squamous cell carcinoma (R/M HNSCC), this multicenter retrospective study aimed to identify clinical, tumor microenvironmental, and genomic factors that are related to therapeutic response to the anti- Programmed cell death protein 1 (PD-1) antibody, nivolumab, in patients with R/M HNSCC. Methods: The study compared 53 responders and 47 non-responders, analyzing formalin-fixed paraffin-embedded samples using 14-marker multiplex immunohistochemistry and targeted gene sequencing. Results: Of 100 patients included, responders had significantly lower smoking and alcohol index, higher incidence of immune related adverse events, and higher PD-1 ligand (PD-L1) expression in immune cells as well as PD-L1 combined positive score (CPS) than non-responders. The frequency of natural killer cells was associated with nivolumab response in patients with prior cetuximab use, but not in cetuximab-naïve status. Age-stratified analysis showed nivolumab response was linked to high CPS and lymphoid-inflamed profiles in patients aged ≥ 65. In contrast, lower NLR in peripheral blood counts was associated with response in patients aged < 65. Notably, TP53 mutation-positive group had lower CPS and T cell densities, suggesting an immune-excluded microenvironment. Patients with altered tumor suppressor gene pathways, including TP53, CDKN2A, and SMAD4 mutations, had lower CPS, higher smoking index, and were associated with poor responses. Conclusion: Nivolumab treatment efficacy in HNSCC is influenced by a combination of clinical factors, age, prior treatment, immune environmental characteristics, and gene mutation profiles.
Subject(s)
Head and Neck Neoplasms , Nivolumab , Squamous Cell Carcinoma of Head and Neck , Tumor Microenvironment , Humans , Tumor Microenvironment/immunology , Nivolumab/therapeutic use , Nivolumab/adverse effects , Male , Squamous Cell Carcinoma of Head and Neck/drug therapy , Squamous Cell Carcinoma of Head and Neck/immunology , Squamous Cell Carcinoma of Head and Neck/genetics , Female , Aged , Middle Aged , Head and Neck Neoplasms/drug therapy , Head and Neck Neoplasms/immunology , Head and Neck Neoplasms/genetics , Retrospective Studies , Biomarkers, Tumor/genetics , Antineoplastic Agents, Immunological/therapeutic use , Antineoplastic Agents, Immunological/adverse effects , Immune Checkpoint Inhibitors/therapeutic use , Immune Checkpoint Inhibitors/adverse effects , Treatment Outcome , Adult , B7-H1 Antigen/genetics , Aged, 80 and over , Mutation , Genomics/methodsABSTRACT
The optimal timing for actively discontinuing immune checkpoint inhibitor therapy in long-term responders with recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) remains unresolved. We conducted a retrospective study of 246 patients with R/M HNSCC treated with nivolumab to determine the optimal timing to actively discontinue nivolumab therapy. We examined the point at which progression-free survival (PFS) plateaued in all cases. We compared the prognosis of 19 (7.7%) ongoing cases and 227 (92.3%) discontinued cases and analyzed treatment duration and treatment-free interval (TFI). The 6-year overall survival was 11.8% (median, 12.1), and the 6-year PFS was 15.3% (median, 3.0). The PFS curve remained stable for 3 years. The median duration of nivolumab treatment was 2.9 months (range 0.03-81.9): Ongoing group, 41.8 (5.6-81.9); Decision group, 36.8 (4.0-70.1); Toxicity group, 30.6 (2.8-64.8); and progressive disease group, 2.0 (0.03-42.9). TFI in the Decision group was 15.1 months (0.6-61.6) and 30.6 months (2.8-64.8) in the Toxicity group. Long-term responses in R/M HNSCC patients treated with nivolumab are rare but gradually increasing. For this patient group, our best estimate of the optimal time to end treatment is 3 years, as the PFS in this study reached a plateau at that timepoint.
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[This corrects the article DOI: 10.1371/journal.pone.0271907.].
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Hypomagnesemia is a characteristic adverse event of cetuximab in patients with head and neck cancer (HNC). However, there is limited information about its prevalence, risk factors, and preventive strategies. This study aimed to investigate the risk factors of hypomagnesemia and examine the preventive effects of prophylactic magnesium (Mg) administration. We initially investigated HNC patients treated with cetuximab between 2013 and 2019. Our institute started prophylactic Mg treatment (20-mEq Mg sulfate administration before cetuximab) in practice during this period. We retrospectively assess the preventive efficacy by comparing patients before and after its implementation. In total, 109 patients were included. In 60 patients without prophylaxis, all-grade and grade ≥2 hypomagnesemia at 3 months occurred in 61.7 and 15.0% of patients. The incidence of hypomagnesemia was not affected by regimens and concomitant medications. In 49 patients treated with prophylactic Mg treatment, there was no significant decrease in the cumulative incidence of hypomagnesemia. However, the preventive Mg treatment eliminated the need for additional Mg repletion to maintain Mg levels in patients treated with paclitaxel + cetuximab. A risk factor in patients without prophylaxis was a low Mg level at pre-treatment (≤2.0 mg/dL) (odds ratio: 6.03, 95% confidence interval: 1.78-20.4, p = 0.004), whereas that in patients with prophylaxis was the number of cetuximab doses (≥10) (odds ratio: 5.50, 95% confidence interval: 1.52-19.87, p = 0.009). In conclusion, a low pre-treatment Mg level was the only risk factor that could be avoided by prophylactic Mg administration. This preventive intervention is recommended for managing cetuximab-induced hypomagnesemia.
Subject(s)
Head and Neck Neoplasms , Magnesium , Humans , Cetuximab/adverse effects , Retrospective Studies , Magnesium/therapeutic use , Antibodies, Monoclonal, Humanized/adverse effects , Head and Neck Neoplasms/drug therapy , Head and Neck Neoplasms/chemically induced , Risk FactorsABSTRACT
Background/Aim: There is limited evidence about the significance of head and neck surgical observation at the time of diagnosis and follow-up of oral cancer after treatment. The aim of this study was to elucidate the prognosis and prognostic factors of oral squamous cell carcinoma (OSCC), analyze cases of double cancers, and highlight the importance of examinations during both diagnosis and post-treatment for OSCC. Patients and Methods: We performed a retrospective analysis of 272 OSCC cases treated for the first time during a 10-year period from April 2013 to March 2023 at Kyushu University Hospital. Information obtained in the clinical setting, such as age, stage, prognosis, and presence of double cancers, was used in the analysis. Results: The mean age of 272 patients was 69 years; 203 patients were males and 69 were females. The most common oral cancer sites were the tongue (54.4%). The 5-year overall survival rate was 63.8%. Double cancer was found in 93 patients (34.2%). Synchronous double cancers were found in 38 patients (14.0%), 50% of whose cancer types were head and neck cancers. Conclusion: We analyzed 272 OSCC patients treated at the Kyushu University Hospital, and the results were comparable to those reported by other institutions. Tumor site, age, and stage were identified as prognostic factors. Half of the patients with synchronous double cancers had head and neck cancer, and 3-10% of patients with double cancers after treatment for OSCC also had head and neck cancer, suggesting the importance of otorhinolaryngological observation at the time of the diagnosis and after treatment.
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BACKGROUND: Rhabdomyosarcoma is the most common soft tissue sarcoma in children, but rare in adults. Para-meningeal rhabdomyosarcoma in head and neck (PM-HNRMS) is less applicable for surgery due to the anatomic reason. PM-HNRMS has a poor prognosis in children. However, its clinical outcomes remain unclear in adults due to the rarity. Further, there is almost no detailed data about salvage therapy. METHODS: We retrospectively examined the adult patients with PM-HNRMS treated at institutions belonging to the Kyushu Medical Oncology Group from 2009 to 2022. We evaluated the overall survival (OS) and progression-free survival (PFS) of the patients who received a first-line therapy. We also reviewed the clinical outcomes of patients who progressed against a first-line therapy and received salvage therapy. RESULTS: Total 11 patients of PM-HNRMS received a first-line therapy. The characteristics were as follows: median age: 38 years (range 25 - 63 years), histology (alveolar/spindle): 10/1, and risk group (intermediate/high): 7/4. As a first-line therapy, VAC and ARST0431-based regimen was performed in 10 and 1 patients, respectively. During a first-line therapy, definitive radiation for all lesions were performed in seven patients. The median PFS was 14.2 months (95%CI: 6.0 - 25.8 months): 17.1 months (95%CI: 6.0 - not reached (NR)) for patients with stage I-III and 8.5 months (95%CI: 5.2 - 25.8 months) for patients with stage IV. The 1-year and 3-year PFS rates were 54.5% and 11.3% for all patients. Median OS in all patients was 40.8 months (95%CI: 12.1 months-NR): 40.8 months (95%CI: 12.1 - NR) for patients with stage I-III and NR for patients with stage IV. The 5-year OS rate was 48.5% for all patients. Among seven patients who received salvage therapy, three are still alive, two of whom remain disease-free for over 4 years after completion of the last therapy. Those two patients received multi-modal therapy including local therapy for all detected lesions. CONCLUSION: The cure rate of adult PM-HNRMS is low in spite of a first-line therapy in this study. Salvage therapy might prolong the survival in patients who received the multi-modal therapy including local therapy for all detected lesions.
Subject(s)
Head and Neck Neoplasms , Rhabdomyosarcoma , Adult , Humans , Middle Aged , Head and Neck Neoplasms/therapy , Japan , Neoplasm Recurrence, Local/therapy , Retrospective Studies , Rhabdomyosarcoma/pathology , Salvage TherapyABSTRACT
INTRODUCTION: Cholesterol granulomas, which frequently present in the temporal bone of the skull, are recognized as benign lesions occurring due to chronic inflammation or hemorrhage. However, cholesterol granuloma of the mediastinum is extremely rare. PRESENTATION OF CASE: An asymptomatic 43-year-old man with an incidental finding of anterior mediastinal mass by positron emission tomography scan was referred to our hospital. Preoperative computed tomography showed a well-circumscribed nodule 2 cm in size in the anterior mediastinum. A total tumor resection through a suprasternal approach was performed. Microscopically, numerous cholesterol clefts with an alveolar-like growth pattern and foreign body reaction were observed, indicating a pathological diagnosis of cholesterol granuloma. DISCUSSION: Cholesterol granuloma is generally thought to be initiated by cell degeneration and hemorrhage resulting from trauma or inflammation. The patient's long-term rugby experience may have played a role in the development of cholesterol granuloma. It is difficult to diagnose a cholesterol granuloma based on preoperative imaging alone, and anatomy often makes preoperative biopsy or cytology difficult. CONCLUSION: Complete resection and pathological examination may be unavoidable for diagnosis and treatment.
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BACKGROUND/AIM: Pembrolizumab monotherapy and pembrolizumab with chemotherapy (combination therapy) are standard treatments for recurrent and metastatic head and neck squamous cell carcinoma (R/M-HNSCC). This study aimed to explore which of the two, pembrolizumab monotherapy or combination therapy is superior for long-term use. PATIENTS AND METHODS: Participants of the study were 139 patients with histologically confirmed squamous cell carcinoma who had been treated with pembrolizumab monotherapy or combination therapy at the Kyushu University and related facilities. We analysed differences regarding long-term survival rate and adverse events (AEs) between the pembrolizumab monotherapy and combination therapy groups. RESULTS: The overall 2-year progression-free survival and 2-year overall survival were 28.6% and 41.8%, respectively; these results were not significantly different between the two groups. Patients in the monotherapy group with AEs had a significantly better prognosis than those without AEs (in both the monotherapy and combination therapy groups). In the combination therapy group, there was no difference in prognosis between those with AEs and those without AEs (p=0.636). CONCLUSION: Considering the treatment of R/M-HNSCC from a long-term perspective, we identified that it is better to use pembrolizumab as monotherapy than to use it in combination with chemotherapy. Combination therapy did not improve prognosis; moreover, it can also cause additional adverse effects.
Subject(s)
Carcinoma, Squamous Cell , Head and Neck Neoplasms , Humans , Squamous Cell Carcinoma of Head and Neck/drug therapy , Neoplasm Recurrence, Local/pathology , Head and Neck Neoplasms/drug therapy , Carcinoma, Squamous Cell/pathology , Antineoplastic Combined Chemotherapy Protocols/adverse effectsABSTRACT
BACKGROUND/AIM: In recent years, individual patient cancer genomic profiling (CGP) has become more accessible, allowing determination of therapeutic strategies using driver gene mutations in cancer therapy. However, this precision oncology approach, tailored to specific patients, remains experimental. In this study, we verified the feasibility and benefit of using CGP to guide treatment of malignant head and neck tumors. We aimed to evaluate the profiling and clinical courses of patients with head and neck malignancies who underwent CGP and determine the extent to which CGP for head and neck malignancies has resulted in beneficial drug administration. PATIENTS AND METHODS: We analyzed CGP results, prognosis, and drug administration status in 27 patients. These patients had completed (or were expected to complete) standard therapy or had rare cancers without standard therapy. RESULTS: At least one somatic actionable gene alteration was seen in 25 (92.6%) patients, with a median number of actionable alterations per patient of 4 (range=0-11). Drugs in clinical trials were recommended to 22 (81.5%) patients, but none could participate. However, 3 patients (11.1%) could use approved drugs off-label based on CGP results. The most common genetic abnormality was TP53 (66.7%), with TP53 mutations leading to poor prognosis. CONCLUSION: CGP is clinically useful and serves as a bridge to increase the number of therapeutic options. However, candidate drugs confirmed using CGP may be ineffective when administered. Therefore, oncologists should not blindly accept CGP therapeutic recommendations but should make recommendations that lead to optimal therapies after proper verification.
Subject(s)
Head and Neck Neoplasms , Precision Medicine , Humans , Precision Medicine/methods , Medical Oncology , Mutation , Head and Neck Neoplasms/drug therapy , Head and Neck Neoplasms/genetics , Genomics/methodsABSTRACT
The prevalence and prognostic significance of high-risk human papillomavirus (HR-HPV) have been well-established in oropharyngeal squamous cell carcinoma (OPSCC), but not in hypopharyngeal squamous cell carcinoma (HPSCC) or laryngeal squamous cell carcinoma (LSCC). Moreover, HR-HPV infection in squamous cell carcinoma with multisite involvement has not been examined. To clarify these issues, we retrospectively collected 480 invasive tumors from 467 patients with HPSCC, LSCC, or OPSCC, and comprehensively analyzed the detailed tumor localization, transcriptionally active HR-HPV infection by messenger RNA in situ hybridization, and immunohistochemical staining for p16 and Rb. HR-HPV infection was observed in 115/480 tumors (24%). Human papillomavirus (HPV)-positive cases were closely related with p16 positivity and the partial loss pattern of Rb. HR-HPV was detected in 104 of 161 tumors (64.6%) in the pure OPSCC group and only 1 of 253 tumors (0.4%) in the pure HP/LSCC group; the positive case occurred in the vocal cords. In the multisite-involving combined-type squamous cell carcinoma group, HPV infection was observed in 10/40 (25%) cases, and the 10 HPV-positive cases had OPSCC extending to the larynx or hypopharynx. Among high T-stage (T3/T4) cases of pure OPSCC, HPV-positive cases showed a better prognosis ( P =0.0144), whereas the HPV-positive combined OPSCC group did not show a better prognosis ( P =0.9428), as compared with HPV-negative counterpart. The results suggest that HR-HPV infection in pure HPSCC and LSCC may be extremely rare. HR-HPV infection seems to be present in a substantial proportion of patients with combined OPSCC and HPSCC/LSCC, but it may not improve prognosis at such advanced disease stages. Confirmation of these points awaits future studies with larger cohorts.
Subject(s)
Carcinoma, Squamous Cell , Head and Neck Neoplasms , Larynx , Oropharyngeal Neoplasms , Papillomavirus Infections , Humans , Papillomavirus Infections/complications , Papillomavirus Infections/epidemiology , Hypopharynx/pathology , Retrospective Studies , Carcinoma, Squamous Cell/pathology , Squamous Cell Carcinoma of Head and Neck , Prognosis , Oropharynx/pathology , Larynx/pathology , Cyclin-Dependent Kinase Inhibitor p16/genetics , Papillomaviridae/geneticsABSTRACT
BACKGROUND/AIM: Lacrimal sac tumors are rare tumor types, with a long time interval from disease onset to diagnosis. We aimed to investigate the characteristics and outcomes of patients with lacrimal sac tumors. PATIENTS AND METHODS: The medical records of 25 patients with lacrimal sac tumors initially treated at the Kyushu university hospital from January 1996 to July 2020 were reviewed. RESULTS: Our analysis included 3 epithelial benign tumors (12.0%) and 22 malignant (88.0%) tumors (squamous cell carcinoma, n=6; adenoid cystic carcinoma, n=2; sebaceous adenocarcinoma, n=2; mucoepidermoid carcinoma, n=1; malignant lymphoma, n=10). The average time from symptom onset to diagnosis was 14.7 months (median=8 months; range=1-96 months). The analysis of patients revealed that lacrimal sac mass (22/25, 88.0%) was the most frequent symptom and a possible tumor marker. Most epithelial benign (n=3) and malignant epithelial (n=12) tumors were treated surgically (14/15, 93.3%). One malignant case was treated with heavy ion beam therapy. Eight patients were treated with postoperative (chemo)radiation therapy because of positive surgical margins (including one unanalyzed case). Local control was ultimately achieved in all but one case. The patient survived for 24 months with immune checkpoint inhibitors and subsequent chemotherapy for local and metastatic recurrence. CONCLUSION: We report our experience in the diagnosis and treatment of lacrimal sac tumors and analyze the clinical trends in cases involving these tumors. Postoperative radiotherapy and pharmacotherapy, including immune checkpoint inhibitors, may be useful for recurrent cases.
Subject(s)
Carcinoma, Squamous Cell , Eye Neoplasms , Lacrimal Apparatus Diseases , Nasolacrimal Duct , Humans , Nasolacrimal Duct/pathology , Lacrimal Apparatus Diseases/diagnosis , Lacrimal Apparatus Diseases/therapy , Immune Checkpoint Inhibitors , Eye Neoplasms/diagnosis , Eye Neoplasms/therapy , Eye Neoplasms/pathology , Carcinoma, Squamous Cell/pathology , Retrospective StudiesABSTRACT
BACKGROUND/AIM: The advent of immune checkpoint inhibitor (ICI) treatment has transformed the treatment of recurrent or metastatic head and neck cancer; however, nasopharyngeal carcinoma (NPC) has not been included in major phase III trials. The clinical outcomes of ICI for NPC in real-world practice remain to be fully elucidated. PATIENTS AND METHODS: We retrospectively reviewed 23 patients with recurrent or metastatic NPC treated with nivolumab or pembrolizumab at 6 institutions from April 2017 to July 2021 and investigated the correlation of clinicopathological factors and immune-related adverse events with the effects of ICI therapy and the prognosis. RESULTS: The objective response rate was 39.1% and the disease control rate was 78.3%. The median progression-free survival was 16.8 months and overall survival has not been reached. As with other treatment procedures, the efficacy and the prognosis tended to be better in EBER-positive cases than in EBER-negative cases. The rate of significant immune-related adverse events that necessitated discontinuation of treatment was only 4.3%. CONCLUSION: ICI monotherapy (e.g., nivolumab and pembrolizumab) was effective and tolerable for NPC in a real-world setting.
Subject(s)
Immune Checkpoint Inhibitors , Nasopharyngeal Neoplasms , Humans , Immune Checkpoint Inhibitors/adverse effects , Nivolumab/adverse effects , Japan , Nasopharyngeal Carcinoma/drug therapy , Retrospective Studies , Nasopharyngeal Neoplasms/drug therapyABSTRACT
BACKGROUND/AIM: Differentiated thyroid cancer (DTC) has a good prognosis, except in the case of patients with radioiodine therapy (RIT)-refractory cancer. However, since DTC is essentially a slowly progressing cancer, it is usually judged to be a DTC with a poor prognosis after multiple RITs and yearly follow-up with echo, computed tomography (CT), and serum thyroglobulin values. This study investigated whether fluorodeoxyglucose-positron emission tomography/CT (FDG PET/CT) combined with initial RIT could identify early-stage patients with poor prognosis. PATIENTS AND METHODS: We evaluated 100 patients with high-risk DTC who underwent total thyroidectomy and received RIT at our institution. We analyzed the clinical outcomes of patients and 18F-FDG accumulation using univariate and multivariate Cox proportional hazards regression models. RESULTS: The 10-year overall survival (OS) was 87.9%, with no significant difference in OS between 18F-FDG accumulation at pre-total or near-total thyroidectomy (NTT) (p=0.180) and 131I accumulation at initial RIT (p=0.577). However, 18F-FDG positive patients had a significantly worse prognosis than negative patients (p=0.005) at initial RIT. CONCLUSION: 18F-FDG PET/CT plays an important role in both the diagnosis and prognostic prediction of RIT refractory disease in DTC patients. 18F-FDG PET/CT can be a useful tool particularly at the time of initial RIT since the 18F-FDG accumulation enables the screening of high-risk DTC with poor prognosis at a very early time stage.
Subject(s)
Adenocarcinoma , Thyroid Neoplasms , Humans , Positron Emission Tomography Computed Tomography , Fluorodeoxyglucose F18 , Iodine Radioisotopes/therapeutic use , Thyroid Neoplasms/diagnostic imaging , Thyroid Neoplasms/radiotherapy , Positron-Emission Tomography , Adenocarcinoma/drug therapyABSTRACT
OBJECTIVE: Early detection of hypopharyngeal squamous cell carcinoma (SCC) is important for both an improved prognosis and less-invasive treatment. We retrospectively analyzed the detection rates of early hypopharyngeal SCCs according to the evaluation methods and the clinical management of early hypopharyngeal SCCs. METHODS: Sixty-eight patients with early hypopharyngeal SCC who were diagnosed were reviewed. RESULTS: The number of early hypopharyngeal cancer patients with asymptomatic or synchronous or metachronous esophageal cancer examined by upper gastrointestinal endoscopy with narrow-band imaging (NBI) was significantly higher than those examined by laryngopharyngeal endoscopy with NBI. The 3-year disease-specific survival rates according to T classification were as follows: Tis, 100%; T1, 100%; T2, 79.8%; and overall, 91.2%, respectively. CONCLUSIONS: Early-stage hypopharyngeal SCC can be cured by minimally invasive transoral surgery or radiotherapy. Observation of the pharynx using NBI in patients with a history of head and neck cancer, esophageal cancer, gastric cancer, or pharyngeal discomfort is very important, and routinely examining the pharynx with NBI, even in patients undergoing endoscopy for screening purposes, is recommended.
Subject(s)
Esophageal Neoplasms , Head and Neck Neoplasms , Hypopharyngeal Neoplasms , Humans , Squamous Cell Carcinoma of Head and Neck , Retrospective Studies , Endoscopy/methods , Esophageal Neoplasms/diagnosis , Esophageal Neoplasms/pathology , Esophageal Neoplasms/therapy , Hypopharyngeal Neoplasms/diagnostic imaging , Hypopharyngeal Neoplasms/therapyABSTRACT
BACKGROUND: Molecular-targeted agents used as a treatment for cancer can cause some rare and serious adverse events such as, delayed wound healing. Depending on the anticancer drug used, temporary withdrawal may be recommended before and after surgery to avoid complications. Once a surgical incision has healed and closed completely, wounds rarely open because of the initiation of molecular targeted therapy several months to years after surgery. Here, we aimed to describe a rare complication of pharyngocutaneous fistula in two patients that was thought to be caused by molecular targeted therapy. CASE PRESENTATION: Case 1 involved a 64-year-old asian man who developed a delayed pharyngocutaneous fistula 3 months after total laryngectomy for laryngeal cancer. Ramucirumab, a vascular endothelial growth factor receptor inhibitor used for recurrent gastric cancer, was speculated to be involved. Case 2 involved a 71-year-old japanese man who developed a delayed pharyngocutaneous fistula 2 years and 1 month after total pharyngeal laryngectomy for pharyngeal cancer. It was speculated that imatinib, a platelet-derived growth factor receptor alpha inhibitor used for chronic myeloid leukemia, was involved. CONCLUSIONS: Although the incidence of late drug-induced anastomotic leakage is very low, when it occurs, it makes oral intake impossible for an extended period and interferes with the appropriate cancer treatment. In this report, we demonstrate the details of these two patients with such a rare complication, which may help accumulate essential data on this topic.
Subject(s)
Cutaneous Fistula , Laryngeal Neoplasms , Pharyngeal Diseases , Male , Humans , Middle Aged , Aged , Molecular Targeted Therapy , Imatinib Mesylate/adverse effects , Vascular Endothelial Growth Factor A , Cutaneous Fistula/chemically induced , Cutaneous Fistula/surgery , Pharyngeal Diseases/chemically induced , Pharyngeal Diseases/surgery , Laryngectomy/adverse effects , Laryngeal Neoplasms/drug therapy , Laryngeal Neoplasms/surgery , Receptors, Platelet-Derived Growth Factor , Postoperative Complications/surgery , Retrospective StudiesABSTRACT
OBJECTIVES: The benefit of sequential therapy after immune checkpoint inhibitor (ICI) treatment for recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) has been recently reported. Furthermore, there is a growing interest in the impact of cetuximab (Cmab)-containing salvage chemotherapy (SCT) and the therapeutic efficacy and adverse events (AEs) of Cmab administration prior to ICI administration. MATERIALS AND METHODS: We retrospectively reviewed the medical records of 52 patients with R/M HNSCC treated with SCT (weekly paclitaxel [PTX], n = 7, or weekly PTX and Cmab [PC], n = 45). RESULTS: The objective response rate (ORR) and a disease control rate (DCR) was 53.3% and 91.1% in the PC group and 42.9% and 57.1% in the PTX group, respectively. There was a significant difference in the DCR between the PC and PTX groups (p = 0.0143). The overall survival (OS) and progression-free survival were significantly better in the PC group than in the PTX group. On the other hand, the incidence of drug-induced interstitial pneumonia (DI-IP) in R/M HNSCC patients who received SCT was 21.2%. Patients in the PC group were divided according to whether they received Cmab (Group A) or did not receive Cmab (Group B) as palliative therapy prior to ICIs. Group B had a significantly better OS than Group A. Furthermore, our findings suggest that the incidence rate of DI-IP during SCT might be higher in Group B. CONCLUSION: Although PC following ICIs shows dramatic efficacy, careful monitoring of AEs, including DI-IP, is recommended.
Subject(s)
Cetuximab , Head and Neck Neoplasms , Immune Checkpoint Inhibitors , Paclitaxel , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Cetuximab/adverse effects , Head and Neck Neoplasms/drug therapy , Head and Neck Neoplasms/etiology , Humans , Neoplasm Recurrence, Local/pathology , Paclitaxel/adverse effects , Retrospective Studies , Squamous Cell Carcinoma of Head and Neck/drug therapy , Squamous Cell Carcinoma of Head and Neck/etiologyABSTRACT
BACKGROUND/AIM: This study investigated the effectiveness of pembrolizumab with or without chemotherapy on advanced-stage head and neck cancer (HNC), including nasopharyngeal, sinonasal cavity and external auditory canal cancer, in a real-world setting. PATIENTS AND METHODS: We retrospectively collected data from 97 HNC patients who were treated with pembrolizumab alone (n=60) or with chemotherapy (n=37), and we investigated the association between clinicopathological findings and treatment response or prognosis. RESULTS: Patients treated with pembrolizumab and chemotherapy had a 1-year overall survival (OS) of 72.8%, objective response rate (ORR) of 48.6%, and serious (≥G3) adverse events (AEs) of 29.7%. Patients treated with pembrolizumab alone had a 1-year OS of 51.9%, ORR of 21.7%, and ≥G3 AEs of 6.7%. Both the ORR and disease control rate (DCR) in the pembrolizumab with chemotherapy group were significantly better than those in the pembrolizumab group (p=0.074 and p=0.00101, respectively). Among patients with distant metastasis, patients on pembrolizumab with chemotherapy achieved significantly better OS than pembrolizumab alone (p=0.0039). Among patients in the pembrolizumab group, both AE-positive and better performance status were associated with longer OS (p=0.011 and p=0.0037, respectively). CONCLUSION: Our real-world experience reinforces the durability and effectiveness of pembrolizumab for HNC patients. Additionally, our results suggest that pembrolizumab with chemotherapy might be recommended for patients with distant metastasis and no prior treatment. Further studies are needed to determine the optimal treatment strategy for HNC.
Subject(s)
Antineoplastic Agents, Immunological , Head and Neck Neoplasms , Lung Neoplasms , Antibodies, Monoclonal, Humanized , Antineoplastic Agents, Immunological/adverse effects , Head and Neck Neoplasms/drug therapy , Humans , Lung Neoplasms/pathology , Retrospective StudiesABSTRACT
BACKGROUND/AIM: A long-term effect has been confirmed in clinical practice since the introduction of nivolumab for treating various malignant tumors. A similar phenomenon is speculated to occur in head and neck cancer; however, details remain unclear due to the lack of long-term reports. We aimed to investigate the five-year outcomes in long-term responders for over two years, and evaluate the optimal duration of therapy with nivolumab. PATIENTS AND METHODS: In this retrospective observational study, we analyzed 203 cases of recurrent/metastatic head and neck squamous cell carcinoma (R/MHNSCC), including 33 long-term responders. RESULTS: The median overall survival (OS), 5-year OS, median progression-free survival (PFS), and 5-year PFS values in the 203 cases were 13.1 months, 19.2%, 3.1 months, and 13.2%, respectively. Of the 33 long-term responders, 14 (42.4%) continued using nivolumab for more than 2 years. The remaining 19 patients (57.6%) discontinued nivolumab. The most common reason for discontinuation was severe immune-related adverse events (irAEs) (9 cases; 27.3%); in these 9 cases, the median disease-free survival was 33.2 (range=10.7-44.3) months. Nine patients (21.2%) were considered to have progressive disease (PD) after at least 2 years of administration, and 3 patients (9.1%) requested to discontinue treatment because a complete response (CR) was achieved. CONCLUSION: This study demonstrated the durable and long-term benefit of nivolumab in R/MHNSCC. In the future, we aim to accumulate real-world data for the establishment of criteria for completion of nivolumab treatment in long-term responders.
Subject(s)
Antineoplastic Agents, Immunological , Carcinoma , Head and Neck Neoplasms , Antineoplastic Agents, Immunological/adverse effects , Carcinoma/drug therapy , Follow-Up Studies , Head and Neck Neoplasms/drug therapy , Humans , Neoplasm Recurrence, Local/pathology , Nivolumab/adverse effects , Retrospective Studies , Squamous Cell Carcinoma of Head and Neck/drug therapyABSTRACT
BACKGROUND/AIM: The inflammation-based prognostic score (IBPS) has attracted attention recently as a prognostic biomarker for head and neck cancer patients. However, as the IBPS often changes after anticancer drug therapy, its independent prognostic value remains controversial. We aimed to investigate the relationship between the IBPS and prognosis in recurrent and/or metastatic head and neck squamous cell carcinoma (RMHNSCC) treated with nivolumab, and investigate changes in the IBPS before and after nivolumab treatment. PATIENTS AND METHODS: Total of 164 patients with RMHNSCC received nivolumab therapy were retrospectively analyzed. RESULTS: Univariate analysis among the 164 patients revealed that the performance status (PS), immune-related adverse event (irAE) status, pre- and post-therapy Glasgow Prognostic Score (GPS), neutrophil-to-lymphocyte ratio (NLR), C-reactive protein-to-albumin ratio (CAR), platelet-to-lymphocyte ratio (PLR), and post-eosinophil count, were all significant predictors of overall survival (OS) (p<0.05). A multivariate analysis revealed that PS, irAEs, post-GPS, post-NLR, post-CAR, and post-eosinophil count were independent prognostic factors for overall survival. CONCLUSION: Post-treatment factors were identified as independent prognostic factors for RMHNSCC and can more accurately predict prognosis compared to nivolumab-treated RMHNSCC pre-treatment factors.
Subject(s)
Antineoplastic Agents, Immunological , Head and Neck Neoplasms , Nivolumab , Squamous Cell Carcinoma of Head and Neck , Antineoplastic Agents, Immunological/therapeutic use , Biomarkers/metabolism , Head and Neck Neoplasms/diagnosis , Head and Neck Neoplasms/drug therapy , Head and Neck Neoplasms/pathology , Humans , Inflammation/pathology , Lymphocytes/pathology , Neoplasm Recurrence, Local/pathology , Nivolumab/therapeutic use , Prognosis , Retrospective Studies , Squamous Cell Carcinoma of Head and Neck/drug therapyABSTRACT
BACKGROUND/AIM: Surgery remains the standard treatment for salivary gland carcinoma (SGC). Our study investigated the association between epidermal growth factor receptor (EGFR) status in recurrent/metastatic SGC and the effectiveness of treatment with cisplatin/carboplatin and 5-fluorouracil plus cetuximab (EXTREME). PATIENTS AND METHODS: We retrospectively collected 19 SGCs from patients treated with the EXTREME regimen. After analyzing EGFR expression and gene copy number gain, we evaluated the correlation between EGFR status and clinicopathological factors and prognosis. RESULTS: EGFR overexpression was detected in 77.8% cases, but not statistically associated with clinicopathological factors or prognosis. EGFR gene copy number gain was detected in 16.7% cases, and statistically positively correlated with lymph node metastasis (p=0.0291). The best overall response was partial response in two cases, stable disease in 15, and progressive disease in one case. The EXTREME regimen was discontinued in all cases. CONCLUSION: Our results suggest that SGCs are positive for EGFR protein expression but the response rate to the EXTREME regimen was unremarkable.