The Armed Forces Institute of Pathology.

European Organization for Research and Treatment of Cancer

Dedifferentiation is a well recognized, if sometimes controversial, form of tumor progression in certain types of soft tissue and bone sarcoma, and confers a worse prognosis when compared with the low-grade counterpart. To date, dedifferentiation has not been described in solitary fibrous tumor (SFT). Among 948 cases of both intrathoracic and extrathoracic SFTs in our files accessioned between 1988 and 2008, we identified 8 cases of conventional SFT with a discrete anaplastic component, which we believe represents dedifferentiation. These occurred in 3 men and 5 women, 40 to 76 years old (median 60 y), and measured 3.4 to 20.0 cm (median 8.5 cm). Two cases were intrathoracic, 2 were located in the deep soft tissue of thigh, and single cases were located in the omentum, scalp, retroperitoneum, and abdominal wall. In addition to typical features of benign-appearing SFT there was an abrupt transition to nondistinctive high-grade sarcoma in all cases. The latter included epithelioid, round cell, and/or spindle cell components with increased mitotic activity, necrosis, and cystic degeneration. By immunohistochemistry, 7 of 8 cases were CD34 positive in the usual SFT areas, whereas 5 showed loss of CD34 in the poorly differentiated component. Six of 7 cases stained for p53 and p16 showed either negative or scattered positive cells in well-differentiated SFT areas, in contrast to positive or stronger and more diffuse staining in the high-grade component. Follow-up information available in 7 patients ranged from 1 to 58 months (mean 24 mo). Three patients with the largest tumors (9.0, 17.0, and 20.0 cm) died of disease, whereas 3 patients whose tumors measured 8.0 cm or less were treated by surgical excision only, and show no evidence of disease but with only limited follow-up. One patient with an 11.5 cm intrathoracic tumor is alive with disease at 58 months after recurrence and metastasis. We describe, apparently for the first time, what seems, at least in our view, to be dedifferentiation in primary SFT. Our results demonstrate that dedifferentiation in SFT, comparable with that in other low grade/intermediate soft-tissue tumors, poses a higher risk of tumor recurrence and/or metastasis, most notably in large and deep-seated tumors. Similar to other dedifferentiated sarcomas, abrupt transition between low grade and high-grade areas is typically observed with loss of CD34 positivity. The p53 and p16 overexpression in the high-grade component is common as in other dedifferentiated lesions, perhaps pertaining to the underlying molecular mechanism.

Expanding the spectrum of malignant progression in solitary fibrous tumors: a study of 8 cases with a discrete anaplastic component--is this dedifferentiated SFT?

Importance Dual blockade of programmed death ligand 1 (PD-L1) and cytotoxic T-lymphocyte associated protein 4 (CTLA-4) may overcome immune checkpoint inhibition. It is unknown whether dual blockade can potentiate antitumor activity without compromising safety in patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) and low or no PD-L1 tumor cell expression. Objective To assess safety and objective response rate of durvalumab combined with tremelimumab. Design, Setting, and Participants The CONDOR study was a phase 2, randomized, open-label study of Durvalumab, Tremelimumab, and Durvalumab in Combination With Tremelimumab in Patients With R/M HNSCC. Eligibility criteria included PD-L1–low/negative disease that had progressed after 1 platinum-containing regimen in the R/M setting. Patients were randomized (N = 267) from April 15, 2015, to March 16, 2016, at 127 sites in North America, Europe, and Asia Pacific. Interventions Durvalumab (20 mg/kg every 4 weeks) + tremelimumab (1 mg/kg every 4 weeks) for 4 cycles, followed by durvalumab (10 mg/kg every 2 weeks), or durvalumab (10 mg/kg every 2 weeks) monotherapy, or tremelimumab (10 mg/kg every 4 weeks for 7 doses then every 12 weeks for 2 doses) monotherapy. Main Outcomes and Measures Safety and tolerability and efficacy measured by objective response rate. Results Among the 267 patients (220 men [82.4%]), median age (range) of patients was 61.0 (23-82) years. Grade 3/4 treatment-related adverse events occurred in 21 patients (15.8%) treated with durvalumab + tremelimumab, 8 (12.3%) treated with durvalumab, and 11 (16.9%) treated with tremelimumab. Grade 3/4 immune-mediated adverse events occurred in 8 patients (6.0%) in the combination arm only. Objective response rate (95% CI) was 7.8% (3.78%-13.79%) in the combination arm (n = 129), 9.2% (3.46%-19.02%) for durvalumab monotherapy (n = 65), and 1.6% (0.04%-8.53%) for tremelimumab monotherapy (n = 63); median overall survival (95% CI) for all patients treated was 7.6 (4.9-10.6), 6.0 (4.0-11.3), and 5.5 (3.9-7.0) months, respectively. Conclusions and Relevance In patients with R/M HNSCC and low or no PD-L1 tumor cell expression, all 3 regimens exhibited a manageable toxicity profile. Durvalumab and durvalumab + tremelimumab resulted in clinical benefit, with minimal observed difference between the two. A phase 3 study is under way. Trial Registration clinicaltrials.gov Identifier:NCT02319044

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Safety and Efficacy of Durvalumab With or Without Tremelimumab in Patients With PD-L1-Low/Negative Recurrent or Metastatic HNSCC: The Phase 2 CONDOR Randomized Clinical Trial.

Purpose Concurrent chemoradiotherapy (CCRT) for squamous cell carcinoma of the head and neck (SCCHN) increases both local tumor control and toxicity. This study evaluates clinical factors that are associated with and might predict severe late toxicity after CCRT. Methods Patients were analyzed from a subset of three previously reported Radiation Therapy Oncology Group (RTOG) trials of CCRT for locally advanced SCCHN (RTOG 91-11, 97-03, and 99-14). Severe late toxicity was defined in this secondary analysis as chronic grade 3 to 4 pharyngeal/laryngeal toxicity (RTOG/European Organisation for the Research and Treatment of Cancer late toxicity scoring system) and/or requirement for a feeding tube ≥ 2 years after registration and/or potential treatment-related death (eg, pneumonia) within 3 years. Case-control analysis was performed, with a multivariable logistic regression model that included pretreatment and treatment potential factors. Results A total of 230 patients were assessable for this analysis: 99 p...

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Factors Associated with Severe Late Toxicity After Concurrent Chemoradiation for Locally Advanced Head and Neck Cancer: An RTOG Analysis

最近，頭頸部マイクロサージャリー術後に早期離床が行われてきている。当院でも2002年9月から段階的にベッド上安静期間を短くし，2004年10月以降は術翌日より安静度の制限をなくし，早期離床を行っている。安静度は2002年9月から2003年9月までの初期，45症例ではICU 2泊，ベッド上安静3日間，離床は4日目で車椅子，歩行開始は5日目であった。2003年10月から2004年9月までの中期，47例では，ICU 1泊，離床は2日目で車椅子，歩行開始は3日目であった。2004年10月以降の後期，164例ではICU 1泊，ベッド上安静を特に行わず，術翌日より歩行開始可能とした。血栓形成は初期で45例中1例（2.2%），中期で47例中1例（2.1%），後期で164例中3例（1.8%）であり，血栓形成率で差はなかった。せん妄は，初期で13例（29%），中期で11例（23%），後期で12例（7%）と，後期で少なかった。早期離床により術後肺炎，無気肺，深部静脈血栓，せん妄などの合併症が減少するため手術後は早期離床が推奨されている。静脈のうっ血の減少や起立性低血圧の減少，頭頸部浮腫の軽減より早期離床は吻合部血栓形成のリスクを減少させる可能性があると考える。

The benefit of postoperative early ambulation after microvascular surgery for head and neck reconstruction

頭頸部癌治療のチーム医療は近年，各施設に浸透しつつある。これには多くのコメディカルが介入しており，各職種の専門業務は患者にとって有益であるが，その労力に見合った妥当な診療報酬が算定できていないのが現状である。頭頸部癌学会評議員を対象にしたアンケートでも，頭頸部癌治療には多職種チーム医療が重要であるが，それに見合った算定ができていないため，診療報酬改定が必要であるという意見が多くを占めた。今後は，頭頸部癌学会の保険委員会などと協力しながら，頭頸部癌治療におけるチーム医療の有効性を証明し，外保連（外科系学会社会保険委員会連合）などにアピールする必要があると思われる。

https://www.jstage.jst.go.jp/article/jjhnc/34/4/34_4_478/_pdf

Yoshiyuki Iida

Papers

The benefit of postoperative early ambulation after microvascular surgery for head and neck reconstruction

Medical economy in head and neck cancer treatment and the promotion of team medical care

Molecular profile of a pleomorphic adenoma of the hard palate: A case report.

Distant metastases in head and neck squamous cell carcinomas after curative treatment

Sclerosing rhabdomyosarcoma of the oral floor mimicking a salivary gland tumor: A case report with immunohistochemical and genetic analyses