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Naomi Hayashi,1 Yasuyoshi Sato,1 Yu Fujiwara,1,2 Naoki Fukuda,1 Xiaofei Wang,1 Kenji Nakano,1 Testuya Urasaki,1 Akihiro Ohmoto,1 Makiko Ono,1 Junichi Tomomatsu,1 Yukiko Sato,3 Hiroki Mitani,4 Takashi Toshiyasu,5 Shunji Takahashi1 1Department of Medical Oncology, The Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan; 2Department of Medicine, Icahn School of Medicine at Mount Sinai, Mount Sinai Beth Israel, New York City, NY, USA; 3Pathology, The Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan; 4Head and Neck Oncology, The Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan; 5Radiation Oncology, The Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, JapanCorrespondence: Yasuyoshi SatoThe Cancer Institute Hospital of Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto, Tokyo, 135-8550, JapanTel +8135200111Fax +81335200141Email yasuyoshi.sato@jfcr.or.jpPurpose: There have been few reports on the evaluation of cancer cachexia based on skeletal muscle mass index (SMI) in patients with head and neck cancer.Patients and Methods: One hundred and ninety-two head and neck cancer patients were enrolled. In definitive and adjuvant chemoradiotherapy settings, clinical outcomes were compared between cachexia and non-cachexia patients.Results: Forty patients were diagnosed with cachexia (20.8%). In the definitive setting, overall survival (OS) was significantly shorter in the cachexia group (3-year OS: 50.0% vs 88.5%; p < 0.01), and multivariate analysis identified UICC stage IV, baseline albumin of < 4 and cachexia as poor prognostic factors. However, cachexia was not significant in the adjuvant setting.Conclusion: Cancer cachexia was negatively associated with prognosis in patients with HNC who received definitive chemoradiotherapy. Nutritional intervention during chemoradiotherapy may improve survival in these patients.Keywords: head and neck cancer, squamous cell carcinoma of head and neck, sarcopenia, cachexia, muscle, skeletal, chemoradiotherapy, prognosis

Background Immune checkpoint inhibitors (ICIs) have become one of the standard treatment options for solid tumours; however, treatment-related adverse events, including pneumonitis, sometimes disrupt the ongoing treatment. To evaluate the impact of ICI addition on the risk of pneumonitis, a meta-analysis was conducted. Methods Phase III randomised controlled trials comparing ICIs and conventional therapy with conventional therapy alone were selected by searching databases, including PubMed, Embase, Web of Science and Cochrane Library. The odds ratio (OR) of any grade and grade III–V pneumonitis was calculated. Meta-analysis was performed to compare the incidence of pneumonitis between the treatment arm with additional ICIs and the arm with conventional therapy. Results A total of 25 randomised controlled trials (RCTs) representing 16,343 patients for grade I–V and 23 RCTs with 15,006 patients for grade III–V pneumonitis were analysed. Adding ICIs was associated with a significant increase in pneumonitis (grade I–V: OR, 2.67, 95% confidence interval [CI]: 2.12–3.37, grade III–V: OR, 1.83, 95% CI: 1.26–2.65). In subgroup analyses based on the mechanism of action of ICIs, cancer types (lung and non-lung cancer) and each ICI, no significant difference in heterogeneity was observed. Conclusions Adding ICIs to the conventional treatment for solid tumours significantly increased both grade I–V and grade III–V pneumonitis regardless of the mechanisms of ICIs and cancer type. These results would be helpful for oncologists to choose the appropriate treatment options using ICIs, particularly for patients with known risk factors of pneumonitis or interstitial lung disease.

Background/aim In the CheckMate-141 trial regarding head and neck cancer (HNC), nivolumab conferred a survival benefit to patients. However, the best treatment sequence of chemotherapy and anti-PD-1/PD-L1 therapy in these cancers is unclear. Patients and methods This was an observational study using data collected prospectively from 97 HNC patients treated with nivolumab at our institutions. Twenty-two HNC patients who received paclitaxel-based chemotherapy before (pre-PTX, n=12) and after (post-PTX, n=10) nivolumab were evaluated. Results The median follow-up time was 15.9 months (range=6.9-35.9 months). There was a significant difference in the overall response rate (ORR) between pre-PTX (17%) and post-PTX (70%) (p=0.027). Similarly, time to progression (TTP) was significantly longer after nivolumab than before nivolumab (post-PTX, 7.4 months; pre-PTX, 4.9 months, p=0.020). Conclusion Paclitaxel-based chemotherapy had a better ORR and TTP after nivolumab than before nivolumab for HNC. The sequential administration of anti-PD-1 therapy followed by paclitaxel-based chemotherapy could be a better strategy for HNC.

Background: Large prospective studies of chemotherapy for metastatic or recurrent adenoid cystic carcinoma (ACC) of the head and neck are lacking due to the rarity of ACC. The aim of this study is to evaluate the efficacy of carboplatin plus paclitaxel toward ACC and perform an exploratory investigation of the prognostic factors to investigate the optimal strategy for metastatic or recurrent ACC.Methods: We retrospectively analyzed recurrent or metastatic ACC patients treated with carboplatin plus paclitaxel between April 2007 and September 2019 in our hospital. Objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS) and overall survival (OS) were evaluated, and an exploratory analysis of the prognostic factors including tumor growth rate (TGR) was conducted.Results: A total of 26 ACC patients were enrolled. ORR and DCR were 11.5% and 76.9%; the median PFS and OS were 8.1 and 22.3 months, respectively. From the results of the multivariate analysis, higher (≥ 6%/month) TGR was associated with worse PFS (hazard ratio [HR] 7.00, 95%CI 1.34–36.53, p = 0.02) and OS (HR 29.33, 95%CI 3.38–254.80, p Conclusions: Carboplatin plus paclitaxel showed modest efficacy for recurrent or metastatic ACC patients. Watchful waiting may be optimal for ACC patients with lower TGR. Systemic chemotherapy should be considered when TGR increases during active surveillance.

BACKGROUND Research is lacking for understanding the health disparities in cancer survivorship in the lesbian, gay, and bisexual (LGB) population in the United States. Self-reported health status is used as a predictor of health disparities. METHODS This secondary data analysis study used 2018 Behavioral Risk Factor Surveillance System data to analyze cancer survivorship characteristics by sexual orientation and sex through the use of logistic regressions. RESULTS Overall, 17,656,329 US cancer survivors were included in this study after weighting, with percentage estimates of 1.52% for gays/lesbians and 1.41% for bisexuals. LGB participants were younger and more ethnically diverse. Significantly, bisexuals had current smoking (32.3% vs 13.6%) and binge drinking rates (17.1% vs 9.1%) twice those of heterosexuals; 16.6% of bisexuals versus 4.1% of heterosexuals reported no health insurance coverage (P < .0001). After adjustments for socioeconomic, health-related behavioral risk, and health care access factors, bisexual females reported poorer general health (odds ratio [OR], 1.33; 95% confidence interval [CI], 1.31-1.36) as well as mental health (OR, 2.43; 95% CI, 2.39-2.46) than their heterosexual peers (P < .0001). Bisexual males were 5.14 times more likely to be told that they had depressive disorders than their heterosexual counterparts (95% CI, 5.05-5.23), whereas bisexual females were 3.23 times more likely for the same outcome (95% CI, 3.18-3.28). All LGB groups reported significantly more inadequate sleep than their heterosexual counterparts (especially lesbians: OR, 2.14; 95% CI, 2.10-2.18). CONCLUSIONS This study indicates that LGB cancer survivors have worse survivorship than their heterosexual peers with heterogeneity in subgroups. Future studies should use larger sample sizes, further investigate disparities, and promote survivorship in LGB populations. LAY SUMMARY It has been observed that lesbian, gay, and bisexual (LGB) cancer survivors may face challenges in cancer survivorship that are not as prevalent in the heterosexual community. This cross-sectional study has found that LGB cancer survivors, especially bisexuals, have overall poorer physical and mental health, are more likely to be told that they have depressive disorders, and have worse sleep quality in comparison with their heterosexual counterparts. These results also differ by sex, and this can provide rationales for future studies and guide interventions to relocate resources to better promote equality.

Objectives: This retrospective observational study is conducted to evaluate the association between cancer cachexia and prognosis in head and neck cancer patients treated with chemoradiotherapy using skeletal muscle mass index at the level of the third lumbar vertebra with computed tomography.Methods: Two hundred forty-two patients were enrolled and categorized into the following four groups based on cancer cachexia criteria and treatment setting: definitive chemoradiotherapy with cachexia, definitive chemoradiotherapy without cachexia, adjuvant chemoradiotherapy with cachexia, and adjuvant chemoradiotherapy without cachexia. Progression-free survival (PFS) and overall survival (OS) between cachexia and non-cachexia groups were compared by treatment setting using the long-rank test. Prognostic factors were evaluated using the Cox proportional hazards model.Results: Fifty patients were diagnosed with cancer cachexia (20.7%). In the definitive setting, both PFS and OS were significantly shorter in the cachexia group (median PFS, 15.5 months vs. not reached, p < 0.01; median OS, 48.4 months vs. not reached. p < 0.01). Conversely, there was no significant difference between the two groups in the adjuvant setting. UICC Stage IV, base of albumin of Conclusion: Cancer cachexia was negatively related with prognosis in patients with head and neck squamous cell carcinoma who received definitive chemoradiotherapy. Nutritional intervention during chemoradiotherapy may improve survival in these patients. Further research is warranted.

Cytotoxic chemotherapy, including cyclophosphamide, vincristine, and dacarbazine (CVD) therapy, is widely used to treat metastatic pheochromocytoma and paraganglioma. Because these diseases are rare, studies are needed to establish treatment strategies. This was a single-center and retrospective study to analyze the efficacy of chemotherapy for patients with metastatic pheochromocytoma and paraganglioma diagnosed in 1983-2020. Clinical characteristics, tumor volume response, biochemical response based on catecholamine level, overall survival, and progression-free survival were evaluated. Patients with a complete response or partial response in tumor volume or catecholamine level were classified as responders. Sixteen patients were administered chemotherapy for a median of 16.5 cycles (interquartile range, 10-42). The tumor volume response was classified as follows: partial response (N = 4), stable disease (N = 9), and progressive disease (N = 3) (disease control rate = 81%). The biochemical responses were as follows: complete response (N = 2), partial response (N = 5), no change (N = 3), and progressive disease (N = 1) (disease control rate = 91%). The 5-year survival rate was 50% (95% confidence interval [CI], 21-74%) and median overall survival was 4.4 years (95% CI, 2.4 years-not reached). Overall survival and progression-free survival between responders and nonresponders were not statistically different. One patient developed myelodysplastic syndrome during CVD therapy. In conclusion, chemotherapy achieved disease control among more than half of patients, although survival did not differ between responders and nonresponders. Further fundamental research and prospective trials are needed to analyze the efficacy of CVD therapy.

Background Head and neck squamous cell carcinoma (HNSCC) is a geriatric cancer. However, older adult patients are frequently underrepresented in large clinical trials. Aims The aim of this study is to assess the efficacy and safety of the EXTREME regimen (platinum + fluorouracil + cetuximab) in older and younger adult patients with HNSCC. Methods and results Patients with recurrent or metastatic HNSCC treated with the EXTREME regimen were retrospectively analyzed. We compare the efficacy and safety in older (aged ≥70 years) younger (aged

Background TAFRO (thrombocytopenia, anasarca, fever, renal insufficiency or reticulin fibrosis, and organomegaly) syndrome is a recently recognized disease with a variety of presentations of variable severity. In acute settings, this disease also involves organ dysfunction because of the associated systemic inflammation. However, cases of TAFRO syndrome with myocardial and/or skeletal muscle calcification have never been reported. Case presentation A 24-year-old healthy young Asian man was admitted with intermittent epigastric pain and fever for 2 weeks. Computed tomography revealed pleural effusion, ascites and systemic lymphadenopathy. Laboratory tests showed thrombocytopenia, elevated C-reactive protein, hypoalbuminemia, anemia and renal dysfunction. Based on these findings and bone marrow biopsy, we diagnosed his disease as TAFRO syndrome and commenced hemodialysis for the renal dysfunction. However, he developed refractory hypocalcemia with unstable vital signs, for which we administered calcium gluconate hydrate. Thereafter, myocardial and skeletal muscle calcification was revealed radiologically, with the myocardial calcification causing sick sinus syndrome. He was treated with tocilizumab and finally discharged in an ambulatory condition after prolonged hospitalization, with residual calcific lesions. Conclusion This is the first report of a patient with TAFRO syndrome and the complication of organ calcification. The etiology of calcification in this case is not clear. Systemic inflammation with possible hypercytokinemia might have been involved in the unexpected complication of systemic calcification. It is important to carefully handle the general management of TAFRO syndrome because of the possibility of various complications.

Portal vein thrombosis (PVT) while using an angiogenesis inhibitor is relatively rare. A 70-year-old Asian man was diagnosed with PVT two months after initiating 5-fluorouracil/leucovorin, irinotecan, and bevacizumab therapy for rectal cancer with liver metastases. Because the metastases were small and shrinking, we suspected that the thrombosis might have been caused by bevacizumab-containing chemotherapy. We stopped bevacizumab and started apixaban, a direct oral anticoagulant (DOAC). Eight months later, the complete dissolution of the thrombus and recanalization of the portal vein were attained. Our case suggests that PVT can occur during bevacizumab-containing chemotherapy, and DOAC therapy might be beneficial for treating PVT in patients with cancer.

Background/Aim: Lenvatinib is one of the few options for patients with anaplastic thyroid cancer (ATC). However, tumor markers for ATC treated with lenvatinib is lacking. The aim of this study was to explore whether the neutrophil-to-lymphocyte ratio (NLR) can be a tumor marker for ATC treated with lenvatinib. Patients and Methods: We retrospectively analyzed the prognostic significance of the NLR in 13 ATC patients treated with lenvatinib. Results: The disease control rate was better in patients with lower NLR (

Background TAFRO syndrome, which was first reported in 2010 in Japan, is a relatively rare disease characterized by thrombocytopenia, anasarca, fever, renal impairment, reticulin fibrosis, and organomegaly. Although this disease is considered similar to multicentric Castleman disease, some of the clinical features, such as thrombocytopenia, are different from typical cases of multicentric Castleman disease. In addition, the etiology of TAFRO syndrome remains unknown and controversial. There have only been a few cases of TAFRO syndrome complicated with adrenal gland lesions, and all of them have had hemorrhagic involvement. Case presentation This report describes the case of a 46-year-old Asian man who presented with fever, epigastric pain, and back pain for 1 month. A computed tomographic scan revealed ascites, mild lymphadenopathy, and left adrenal necrosis without hemorrhage. A blood test showed thrombocytopenia, anemia, and elevated C-reactive protein, alkaline phosphatase, and creatinine levels. Based on the edema, severe thrombocytopenia, fever, reticulin myelofibrosis shown by bone marrow biopsy, mild lymphadenopathy, and progressive renal insufficiency, we diagnosed this patient as having TAFRO syndrome. He was successfully treated by immediate administration of glucocorticoids and tocilizumab. Conclusions There have been no previous reports of a case of TAFRO syndrome complicated with adrenal necrosis. Because the biopsy of the left adrenal gland revealed necrosis without any evidence of hemorrhage, we concluded that the unilateral adrenal necrosis in this case was caused by either ischemia from infarction or organomegaly itself under severe hypercytokinemia. This unusual clinical course is useful for further analysis of the etiology of TAFRO syndrome.

Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of cancer over the last decade, bringing about a paradigm shift in systemic cancer therapy away from traditional cytotoxic and targeted therapies. While some patients have dramatic treatment responses, it is sobering to note that most tumors are either resistant at the outset, or develop resistance after initial response. A major area of translational and clinical research is in identifying therapeutic strategies to overcome resistance to ICIs. We have performed an in-depth review of the different mechanisms of resistance and potential avenues to overcome resistance through rationally designed combination treatment with ICIs.

It is known that prostate cancer usually presents as adenocarcinoma, frequently metastasizes to bone, appears osteoblastic on radiographs, and shows elevated PSA. Herein, we describe a case of an 80-year-old man diagnosed with prostate cancer presenting as adenocarcinoma and small cell carcinoma in different areas as well as osteolytic bone metastases in the ilium, right rib, vertebrae, and bilateral femurs with markedly elevated CEA (2391 ng/mL) and Pro-GRP (2610 pg/mL). Occasionally, prostate cancer can appear as osteolytic bone metastases, and in this case, it is possible that the prostate cancer contained small cell carcinoma.

2645 Background: Immune checkpoint blockade (ICB) has emerged as a promising treatment strategy for many solid tumors. Although safe for many patients, ICB causes immune-related adverse events (irAEs) including hepatitis, which may result in morbidity and treatment disruption. Severe hepatitis requires immunosuppression, including corticosteroids and mycophenolate mofetil. We conducted a meta-analysis of clinical trials to investigate the effect of adding ICB to conventional solid tumor therapy on the incidence of hepatitis. Methods: Phase 3 randomized clinical trials (RCTs) comparing ICB and conventional therapy to conventional therapy alone were chosen by database search on PubMed, Embase, Web of Science, and Cochrane Library. The odds ratios [OR] of any-grade and grade ≥3 hepatitis, elevated aspartate aminotransferase (AST), and elevated alanine aminotransferase (ALT) were calculated. Meta-analysis was conducted to determine the incidence of hepatitis, elevated AST, and elevated ALT among patients receiving ICB and those receiving conventional therapy alone. Subgroup analysis based on the mechanism of ICB (Cytotoxic T-lymphocyte-associated protein 4 [CTLA-4] inhibitor, programmed cell death protein 1 [PD-1] inhibitor, and programmed death-ligand 1 [PD-L1] inhibitor) was also conducted. Results: A total of 29 randomized controlled trials (RCTs) enrolling 18,829 participants were analyzed. Incidence of hepatitis was derived from 24 RCTs enrolling 15,183 patients, and incidence of grade ≥3 hepatitis was derived from 22 RCTs enrolling 13,846 patients. Incidence of elevated AST was extracted from 18 RCTs, and incidence of elevated ALT was extracted from 20 RCTs. Addition of ICB to conventional therapy was associated with an increase in incidence of any-grade hepatitis (OR 2.54, 95% confidence interval [CI] 1.82-3.55) and grade ≥3 hepatitis (OR 4.22, 95% CI 2.51-7.11). The addition of ICB was also associated with an increase in incidence of elevated AST (any grade: OR 2.19, 95% CI 1.59-3.03; grade ≥3: OR 3.18, 95% CI 1.85-5.48) and elevated ALT (any grade: OR 2.08, 95% CI 1.47-2.92; grade ≥3: OR 2.41, 95% CI 1.40-4.14). Subgroup analysis based on the mechanism of ICB demonstrated increased incidence of grade ≥3 hepatitis associated with CTLA-4 inhibitor, PD-1 inhibitor, and PD-L1 inhibitor therapy (OR 2.78, 95% CI 1.26-6.14; OR 6.30, 95% CI 2.23-17.78; OR 4.73, 95% CI 1.83-12.23, respectively). No significant difference of heterogeneity was observed among subgroups ( I2= 0%, p = 0.43). Conclusions: Addition of ICB to conventional solid tumor therapy was associated with increased incidence of any-grade and severe hepatitis, and elevations of AST and ALT, regardless of the mechanism of ICB. Clinicians should weigh the risk of liver toxicity when considering addition of ICB therapy in patients with solid tumors.

e18007 Background: Concurrent chemoradiotherapy (CCRT) with cisplatin (CDDP) is a standard treatment for locally advanced head and neck cancer (LAHNC) in the definitive setting. Three cycles of 100 mg/m2 CDDP for every three weeks (Q3W) are now recommended but compliance with CCRT is relatively low due to its severe toxicity. Therefore, the potential de-escalation strategies for LAHNC have been discussed to decrease the therapeutic toxicity. Methods: Patients with LAHNC who underwent definitive CCRT with CDDP between 2012 and 2018 at The Cancer Institute Hospital of Japanese Foundation for Cancer Research were analyzed. Patients were classified into two groups based on the planned CDDP dose: (A) 100 mg/m2 and (B) 80 mg/m2 Q3W for three times. One-to-one propensity score matching was performed to minimize bias between two groups. After patients in two groups were matched by using propensity score, the overall survival (OS), recurrence-free survival (RFS), local recurrence-free survival (LRFS), and metastatic recurrence-free survival (MRFS) were analyzed by the Kaplan-Meier method with the Cox proportional hazards model. The follow-up term was set as two years to evaluate the early survival benefit. The dose and density of CDDP and the objective adverse events were also assessed. Results: A total of 304 patients were included with the median age of 62 (Interquartile range [IQR]: 54-67) years. Among them, 249 patients (82%) were male. Patients were treated with 100 mg/m2 CDDP (n = 145) and 80 mg/m2 CDDP (n = 159) regimens. After the propensity score matching, 119 patients were included in each group, respectively. There were no significant differences in baseline characteristics between two propensity-matched cohorts. The median follow-up time was 24 months in each group. Two-year OS was 93.0% (95% confidence interval [CI]: 88.4-97.8) in group A and 94.9% (91.0-99.0) in group B. Two-year RFS was 86.5% (80.6-92.9) in group A and 83.1% (76.6-90.1) in group B, respectively. No significant difference was observed in OS (Hazard ratio [HR] = 1.42, 95% CI: 0.49-4.08, p = 0.52), RFS (HR = 0.81, 95% CI: 0.42-1.57, p = 0.54), LRFS (HR = 0.57, 95% CI: 0.24-1.36, p = 0.20), and MFS (HR = 1.32, 95% CI: 0.52-3.35, p = 0.56). The median cumulative dose of CDDP was significantly higher in group A (300 mg, interquartile range [IQR]: 240-300) than in group B (240 mg, IQR:160-240) but the frequency of hematological, hepatic, renal, electrolytic, and grade 3-5 any adverse events was not significantly different between two groups. Conclusions: Our study showed no survival difference at 2-year follow-up between 100 mg/m2 and 80 mg/m2 CDDP regimens of definitive CCRT for LAHNC. This result could support the tide of the de-escalation strategy in head and neck cancer treatment. Longer follow-up is necessary and further prospective trials comparing CDDP dosage are warranted.

The risk of malignancy in inflammatory myopathy patients is well recognized. However, the incidence of germ cell tumor (GCT) with inflammatory myopathy is low, and most reported cases of GCT also exhibit testicular tumors. Therefore, a case of extragonadal GCT with dermatomyositis (DM) is reported in the current study to better understand this paraneoplastic syndrome. A 53-year-old man presented with bilateral cervical lymph node enlargement. A lymph node biopsy showed embryonal carcinoma, and computed tomography showed multiple lymph node and lung metastases. A period of one month after bleomycin, etoposide and cisplatin (BEP) chemotherapy, this patient developed an erythematous eruption over the extensor surfaces of bilateral fingers, or Gottron's sign and facial erythema. The patient was diagnosed with DM with a positive anti-TIF-1γ-antibody result. High-dose prednisolone was effective, and there has been no evidence of cancer recurrence for over one year. The literature review identified 17 cases of GCT with inflammatory myopathy that have been reported so far, and it was indicated that this is the first case of extragonadal GCT with DM following chemotherapy. This case highlights the importance of monitoring after the completion of cancer treatment, as distinctive dermal and muscular symptoms should cause us to consider the possibility of paraneoplastic inflammatory myopathy.