Stereotactic body radiotherapy and checkpoint inhibitor for locally recurrent unresectable nasopharyngeal carcinoma.

The treatment of local recurrence of nasopharyngeal carcinoma (NPC) is challenging, and the role of reirradiation is controversial regarding the high risk for severe toxicity. Stereotactic body radiotherapy (SBRT) is a high-precision radiation technique that can spare surrounding normal tissues. Studies have demonstrated the high activity and low toxicity of both SBRT and anti-programmed-cell-death-1 immune checkpoint inhibitors for head and neck cancers. There has been preclinical and clinical evidence suggesting synergy between radiotherapy and checkpoint inhibitors. We report two patients with locally recurrent unresectable rT4 NPC both involving the retro-orbital areas. They received the same treatment with low-dose SBRT (28 Gy in 5 fractions) and pembrolizumab, and showed a remarkable tumour response without untoward radiation toxicity. SBRT plus an immune checkpoint inhibitor may provide a new treatment option for locally recurrent NPC. We propose further investigation with a formal clinical trial.

Evaluation of Rare and Common Variants from Suspected Familial or Sporadic Nasopharyngeal Carcinoma (NPC) Susceptibility Genes in Sporadic NPC.

BACKGROUND: Genetic susceptibility is associated with nasopharyngeal carcinoma (NPC). We previously identified rare variants potentially involved in familial NPC and common variants significantly associated with sporadic NPC. METHODS: We conducted targeted gene sequencing of 20 genes [16 identified from the study of multiplex families, three identified from a pooled analysis of NPC genome-wide association study (GWAS), and one identified from both studies] among 819 NPC cases and 938 controls from two case-control studies in Taiwan (independent from previous studies). A targeted, multiplex PCR primer panel was designed using the custom Ion AmpliSeq Designer v4.2 targeting the regions of the selected genes. Gene-based and single-variant tests were conducted. RESULTS: We found that NPC was associated with combined common and rare variants in CDKN2A/2B (P = 1.3 × 10-4), BRD2 (P = 1.6 × 10-3), TNFRSF19 (P = 4.0 × 10-3), and CLPTM1L/TERT (P = 5.4 × 10-3). Such associations were likely driven by common variants within these genes, based on gene-based analyses evaluating common variants and rare variants separately (e.g., for common variants of CDKN2A/2B, P = 4.6 × 10-4; for rare variants, P = 0.04). We also observed a suggestive association with rare variants in HNRNPU (P = 3.8 × 10-3) for NPC risk. In addition, we validated four previously reported NPC risk-associated SNPs. CONCLUSIONS: Our findings confirm previously reported associated variants and suggest that some common variants in genes previously linked to familial NPC are associated with the development of sporadic NPC. IMPACT: NPC-associated genes, including CLPTM1L/TERT, BRD2, and HNRNPU, suggest a role for telomere length maintenance in NPC etiology.

The Impact of First Complete Remission by PET-CT and Time to Next Treatment on Survival of Follicular Lymphoma Patients.

We retrospectively analyzed the impact of initial positron emission tomography and computed tomography (PET-CT) complete remission (CR) and time to next treatment (TTNT) on patient outcome in follicular lymphoma. Between 2002 and 2014, 150 patients could be evaluated for treatment response and long-term outcome. The CR after first line treatment with either rituximab-cyclophosphamide, oncovin, and prednisolone (R-COP) or rituximab-cyclophosphamide, doxorubicin, oncovin, and prednisolone (R-CHOP) was 89% and partial response (PR) was 7%. The 5- and 10-year survival rates were 86.0% and 62.6%, respectively. In five years, 11% of patients had died of lymphoma and 3% from other causes. Forty-seven patients (31%) underwent a second line of treatment comprising 19 (40%) with a TTNT shorter than 24 months and 28 (60%) longer than 24 months. There was no difference in overall survival (OS) between R-COP (86%) and R-CHOP (77%) at 5 years, but there were more next treatment events in the R-COP compared with the R-CHOP group on longer follow-up (60% versus 35% at 8 years). For PET-CT response, there was a significant OS difference between initial CR and PR patients (88% versus 70%, p < 0.01), and a longer TTNT was seen in initial CR patients. Patients with a TTNT longer than 24 months had better OS compared with patients with a shorter TTNT (93% versus 54% at 5 years, p < 0.01). In conclusion, patients with initial PET-CT CR and TTNT longer than 24 months had better OS compared with those achieving only PR and shorter TTNT. PET-CT CR should be considered the treatment goal during initial treatment, and more aggressive treatment should be considered for patients with a TTNT of less than 24 months.

Survival without adjuvant chemotherapy for selected patients with stage II and III nasopharyngeal carcinoma after concurrent chemoradiotherapy alone.

BACKGROUND: The role of adjuvant chemotherapy after concurrent chemoradiotherapy (CRT) for nasopharyngeal carcinoma (NPC) is controversial. We report our phase II prospective study of withholding adjuvant chemotherapy in a subgroup of patients with American Joint Committee on Cancer (AJCC) stage II and III NPC with low risk for metastasis. METHODS: Between April 1998 and December 2008, 263 patients with stage II (AJCC 1997 T2aN0, T1-T2aN1; AJCC 2010 T1N1) NPC or stage III (AJCC 1997 T1-T2aN2; AJCC 2010 T1N2) NPC were enrolled. Patients received standard concurrent CRT with cisplatin and 5-fluorouracil (5-FU) but without adjuvant chemotherapy. RESULTS: With a median follow-up of 107 months, the 5-year overall survival (OS), disease-free survival (DFS), and distant metastasis-free survival (DMFS) were 92.4%, 84.4%, and 90.7% for all patients; 94.1%, 85.9%, and 92.9% for patients with stage II NPC; and 90.9%, 83.2%, and 88.9% for patients with stage III NPC, respectively. CONCLUSION: It is safe to withhold adjuvant chemotherapy for selected patients with stage II and III NPC.

Clinicopathologic features and treatment outcome of non-Hodgkin lymphoma of the breast--a review of 42 primary and secondary cases in Taiwanese patients.

Breast lymphoma is a rare form of non-Hodgkin lymphoma (NHL). However, its clinicopathologic features, treatment, patterns of failure and prognosis remains unclear. We reviewed the clinicopathologic features, treatment variables, failure patterns and the clinical outcome of all cases of breast NHL diagnosed in three institutions in Taiwan between 1984 and 2006. The diagnosis, based on the criteria proposed by Wiseman and Liao, was primary breast lymphoma (PBL) in 23 patients and secondary breast lymphoma (SBL) in 19. Diffuse large B-cell lymphoma was the predominant histological type of both. Among patients with PBL, 18 received chemotherapy and radiotherapy, 3 received chemotherapy alone and 2 received radiotherapy alone. In contrast, all 19 patients with SBL received chemotherapy alone. At a median follow-up of 4.4 years, patients with PBL had a significantly better 5-year event-free survival and overall survival. The contralateral breast was the predominant site of recurrence for patients with PBL. In multivariate analyses, young age and stage IIE disease were significantly associated with poorer prognosis of PBL. Our results indicate combined modality treatment results in a favourable outcome for patients with PBL. Further investigation of underlying mechanisms of young age- and stage IIE disease-related poor prognosis in patients with PBL is needed.

Prognostic factors in extrapulmonary small cell carcinomas. A large retrospective study.

BACKGROUND: Extrapulmonary small cell carcinoma (EPSCC) is a heterogeneous group of cancers. The clinicopathological features of EPSCC remain poorly defined. PATIENTS AND METHODS: Patients with the clinicopathological features of EPSCC, treated at three major medical centers in Taiwan, were included. Histologic and clinical diagnoses, smoking history, staging, clinical course and treatment outcome were reviewed and analyzed. RESULTS: A total of 90 patients, treated between 1995 and 2005, were eligible for analysis. Forty-nine patients had limited disease and 41 extensive disease. Ten, 18, 17 and 45 patients received no treatment, local treatment, chemotherapy alone or combined modality treatment, respectively; the median survival for these four groups was 1.1, 13.8, 6.7 and 24.9 months. The origin of cancer was head and neck in 17, gastrointestinal in 27, genitourinary in 10, gynecologic in 27 and unknown in 9 patients; the median survival time was 34.2, 6.4, 9.1, 23.7 and 9.2 months, respectively. Ten out of 90 patients were long-term survivors, and 9 of them had tumors of head-and-neck and gynecologic origin. There was no statistically significant difference in survival between smokers and non-smokers. Factors associated with survival in univariate analysis included age < or =60, female gender, limited disease, head-and-neck and gynecologic origin, as well as combined modality treatment. However, in multivariate analysis, only female gender, limited disease and combined modality treatment were independent predictors of survival. CONCLUSIONS: Female gender, limited disease and combined modality treatment are favorable prognostic factors for patients with EPSCC. Prolonged survival is more likely in patients with tumors of head-and-neck and gynecologic origin.