Three-year Progression-free Survival Research Articles

Nab-Paclitaxel-based induction chemotherapy followed by cisplatin and radiation therapy for human papillomavirus-unrelated head and neck squamous-cell carcinoma.

In patients with locally advanced human papillomavirus (HPV)-unrelated head and neck squamous-cell carcinoma (HNSCC), cisplatin and radiation therapy (CisRT) resulted in a local-regional recurrence (LRR) rate of 35%, progression-free survival (PFS) of 49%, and overall survival (OS) of 60%. We, and others, showed that nab-paclitaxel is an active agent in metastatic and locally advanced HNSCC. The aim of this report was to assess the efficacy of nab-paclitaxel-based induction chemotherapy and CisRT in HPV-unrelated HNSCC. We performed a retrospective single-institution analysis of patients treated with nab-paclitaxel-based chemotherapy and CisRT. Key inclusion criteria included stage III-IV HPV-unrelated HNSCC. Induction chemotherapy included nab-paclitaxel and cisplatin (AP), AP + 5-fluorouracil (APF), or APF + Cetuximab (APF-C). Endpoints included LRR, overall relapse, PFS, and OS. Thirty-eight patients were the subject of this analysis. Patient characteristics included median age 59years (IQR: 54-64) and smoking history in 36 patients (95%). Primary tumor sites included larynx/hypopharynx (27), p16 negative oropharynx (10), and oral cavity (1). Most patients had bulky disease: 82% T3-4 (n = 31) and 74% N2b-3 (n = 28). Median follow-up was 44months (IQR: 23-59). The three-year LRR rate was 16% (95% confidence interval [CI] 7-34) and the overall relapse rate was 22% (95% CI 11-41). The three-year PFS was 64% (95% CI 46-77) and OS was 72% (95% CI 54-84). Among patients with HPV-unrelated HNSCC, nab-paclitaxel-based induction chemotherapy and CisRT resulted in a lower-than-expected rate of LRR and more favorable PFS and OS compared to historical results with CisRT.

Impact of Proton Beam Irradiation of an Anatomic Subsegment of the Liver for Hepatocellular Carcinoma

PurposeThe objective of this research was to elucidate the impact on the prognosis, including the survival prognosis, resulting from proton beam irradiation of an anatomic subsegment of the liver (ASPT) for the treatment of hepatocellular carcinoma (HCC). Methods and MaterialsA total of 110 patients who received a diagnosis of HCC were analyzed in this retrospective study. Definitive proton beam therapy was delivered at a dose of 76 Gy (relative biological effectiveness) in 20 fractions between January 2008 and December 2015. When the HCC widely abutted blood vessels or when multiple HCC tumors occurred within the same liver subsegment, the clinical target volume was outlined as an anatomic subsegment of the liver, according to the portal territory, containing the tumor. In the remaining cases, the clinical target volume was delineated by adding a 5-mm margin around the gross tumor volume. The overall survival (OS), progression-free survival (PFS), and local control rates and adverse events were assessed. A review of the medical charts assessed adverse events that occurred during and after the treatment and were classified according to the Common Terminology Criteria for Adverse Events version 4.0. ResultsThe median follow-up duration was 36.5 months (range, 1-90.6 months). The median age of the patients was 73 years (range, 48-90 years). ASPT was performed in 31 patients (28%). Three-year OS, PFS, and local control rates were 74.2%, 40.4%, and 91.7%, respectively. Multivariate analysis identified ASPT as a factor that significantly improved PFS (P = .049) but not OS (P = .79). No association was found between ASPT and the frequency of grade ≥3 acute/late adverse events. ConclusionsASPT was associated with a reduction in the rate of tumor progression and no significant toxicity but was not associated with OS.

L1CAM expression in colorectal cancer identifies a high-risk group of patients with dismal prognosis already in early-stage disease

Background: Metastatic disease in colorectal cancer represents a major cause of significant cancer-associated morbidity and mortality. L1CAM is a stem cell marker, cell adhesion molecule, belongs to the immunoglobulin superfamily of cell adhesion molecules (IgCAM) and it is aberrantly expressed in several different types of human solid tumors. The aim of the present study was to assess the expression patterns of L1CAM and its clinical significance in colorectal cancer.Patients and methods: Surgical specimens of 109 patients with primary resectable colorectal cancer were examined for L1CAM expression via immunohistochemistry and the results were correlated with clinical and survival data.Results: L1CAM expression was significantly correlated with advanced stage of disease (p < .001), higher T classification (p = .040), the presence of lymph node (p < .001) and distant metastasis (p = .011). Patients displaying high L1CAM expression demonstrated a dismal three-year progression free survival (29.7% vs 87.1%, p < .001) and five-year overall survival (39.9% vs 87.7%, p < .001). Multivariate analysis using Cox proportional hazard models revealed high L1CAM expression as a prognostic marker of dismal progression free (HR 0.187, 95%CI = 0.075–0.467, p < .0001) and overall survival (HR 0.154, 95%CI = 0.049–0.483, p = .001) independent of other clinicopathological characteristics. Subgroup analysis comprised of patients with early stage disease only presented as well significantly worse progression free and overall survival when L1CAM exhibited high expression.Conclusions: Colorectal cancer patients displaying high expression of L1CAM harbor high risk for metastasis already in early stage disease identifying therefore a group of patients prone to dismal prognosis.

Ipsilateral Neck Irradiation for Postoperative Lateralized Buccal Mucosa Squamous Carcinoma with Extranodal Extension: Propensity Analysis

The presence of extranodal extension (ENE) is the most significant risk factor for tumor control in head and neck squamous cell carcinoma (HNSCC). Concomitant chemoradiotherapy has been the standard of care for postoperative HNSCC. However, ipsilateral or bilateral radiotherapy for well-lateralized HNSCC is still controversial. We try to evaluate whether ipsilateral irradiation is safe for ENE-positive patients with well-lateralized buccal mucosa squamous cell carcinoma (BMSCC). Data of 186 well-lateralized BMSCC patients with ENE treated by postoperative ipsilateral RT or bilateral RT from January, 1997 to December, 2016 were included in this retrospective analysis. Patients in both arms were matched using the propensity score method, with 1:2 ratio matching from the ipsilateral RT group and the bilateral RT group in 10 key clinicopathological features. All outcomes were evaluated from the date of radical surgery. Primary endpoint was three-year contralateral neck control (CLNC). Secondary endpoints were three-year overall survival (OS), progression free survival (PFS), local control (LC), regional control (RC) and distant metastasis-free survival (DMFS). After matching, 123 patients (45 patients in ipsilateral RT group and 78 patients in bilateral RT group) were selected for analysis. The median follow-up time was 36.3 months (range 3.6-218.5). Cox regression analysis revealed that ENE number ≥ 4 is the only prognostic factor in all endpoints. RT field (ipsilateral RT vs. bilateral RT) did not have impact in three-year CLNC (85.6% vs. 89.1%, p = 0.75), OS (53.2% vs. 57.4%, p = 0.23), PFS (46.5% vs. 48.6%, p = 0.52), LC (74.6% vs. 77.4%, p = 0.78), RC (79.9% vs. 76.2%, p = 0.47) and DMFS (70.7% vs. 72.0%, p = 0.50). Ipsilateral neck irradiation treatment did not have worse outcomes for the postoperative BMSCC patients with ENE compared with bilateral neck treatment. The number of ENE is the most important prognostic factor in postoperative BMSCC patients with ENE.

Patterns of failure after immunotherapy with checkpoint inhibitors predict durable progression-free survival after local therapy for metastatic melanoma

BackgroundCheckpoint inhibitors (CPI) have revolutionized the treatment of metastatic melanoma, but most patients treated with CPI eventually develop progressive disease. Local therapy including surgery, ablation or stereotactic body radiotherapy (SBRT) may be useful to manage limited progression, but criteria for patient selection have not been established. Previous work has suggested progression-free survival (PFS) after local therapy is associated with patterns of immunotherapy failure, but this has not been studied in patients treated with CPI.MethodsWe analyzed clinical data from patients with metastatic melanoma who were treated with antibodies against CTLA-4, PD-1 or PD-L1, either as single-agent or combination therapy, and identified those who had disease progression in 1 to 3 sites managed with local therapy. Patterns of CPI failure were designated by independent radiological review as growth of established metastases or appearance of new metastases. Local therapy for diagnosis, palliation or CNS metastases was excluded.ResultsFour hundred twenty-eight patients with metastatic melanoma received treatment with CPI from 2007 to 2018. Seventy-seven have ongoing complete responses while 69 died within 6 months of starting CPI; of the remaining 282 patients, 52 (18%) were treated with local therapy meeting our inclusion criteria. Local therapy to achieve no evidence of disease (NED) was associated with three-year progression-free survival (PFS) of 31% and five-year disease-specific survival (DSS) of 60%. Stratified by patterns of failure, patients with progression in established tumors had three-year PFS of 70%, while those with new metastases had three-year PFS of 6% (P = 0.001). Five-year DSS after local therapy was 93% versus 31%, respectively (P = 0.046).ConclusionsLocal therapy for oligoprogression after CPI can result in durable PFS in selected patients. We observed that patterns of failure seen during or after CPI treatment are strongly associated with PFS after local therapy, and may represent a useful criterion for patient selection. This experience suggests there may be an increased role for local therapy in patients being treated with immunotherapy.

Comprehensive geriatric assessment is useful in an elderly Australian population with diffuse large B-cell lymphoma receiving rituximab-chemotherapy combinations.

Elderly patients may be heterogeneous in their abilities to tolerate immunochemotherapy-associated toxicities. We describe the morbidity of rituximab-chemotherapy combinations among 205 newly-diagnosed diffuse large B-cell lymphoma (DLBCL) patients aged ≥60years from 3 tertiary hospitals between 2009 and 2016, and explore the utility of retrospectively-assigned baseline Comprehensive Geriatric Assessment (CGA) in predicting these toxicities. Seventy-three percent (146/201) experienced grade ≥3 toxicities, 81% (163/201) needed admission, 52% (107/205) had ≥2 unplanned admissions, 82/201 (41%) required dose reductions (DR) subsequent to Cycle 1, 39/166(23%) had chemotherapy delays and 26/198(13%) ceased therapy early. CGA was associated with pre-emptive baseline DR and perhaps because of this, did not predict grade ≥3 toxicities, ≥2 unplanned admissions or subsequent DR. Three-year overall survival (OS) of CGA-fit, CGA-unfit and CGA-frail patients was 82%, 60% and 53%, respectively. Three-year progression-free survival (PFS) of CGA-fit, CGA-unfit and CGA-frail patients was 66%, 58% and 46%, respectively. OS of CGA-fit patients was not statistically different from CGA-unfit patients, but was superior to CGA-frail patients (hazard ratio 2·892, 95% confidence interval 1·275-6·559, P=0·011). PFS differences were not statistically significant. Baseline DR and early therapy cessation were associated with inferior OS and PFS independent of CGA. Prospective studies are needed to confirm if CGA-adapted treatment strategies minimize morbidity and improves survival.

Impact of next-generation sequencing (NGS) in patients with high grade glioma.

e13541 Background: Clinical utility of NGS in high grade glioma patients remain debatable. Methods: We reviewed patients who underwent Foundation One NGS between 7/2013 and 10/2018 after high-grade glioma diagnosis at Cleveland Clinic. Overall survival (OS) and progression free survival (PFS) were estimated by the Kaplan-Meier method and compared by log-rank test. Cox regression analysis was performed to identify predictors of OS. Results: We identified 153 patients, 130 (85%) had glioblastoma multiforme (GBM) and 23 (15%) had grade III glioma, 51 (33%) were female, and median age at diagnosis was 58 (range: 18 – 92). Sixteen (10%) patients had secondary glioma and 34 (22%) had multilobar involvement. ECOG performance score at diagnosis was 0 or 1, 2, and ≥ 3 for 79 (52%), 54 (35%), and 13 (9%) patients, respectively. Glioma was surgically resected for 112 (73%) patients, 85 (56%) had total and 27 (18%) had subtotal resection, whereas other 41 (27%) patients underwent biopsy only. Radiotherapy, temozolomide, and bevacizumab were given to 132 (86%), 129 (84%), and 67 (44%) patients, respectively. NGS revealed median of 5 mutated genes (range: 0 – 19), commonly mutated genes were TERT (63%), CDKN2AB (60%), EGFR (42%), TP53 (42%), PTEN (38%), and IDH1/2 (20%). Two patients received bevacizumab for KDR amplification, 1 received off-label lapatinib for EGFR amplification, and 3 received off-label everolimus for multiple mutations. Median follow-up was 18 months. Three-year OS and PFS for patients with GBM vs grade III glioma were 29% (95% CI: 22 – 39) vs 78% (95% CI: 63 – 97) and 17% (95% CI: 11 – 25) vs 74% (95% CI: 58 – 94), respectively (p &lt; 0.0001 for both). On univariable analysis, each 10 increase in age, ECOG ≥3 vs &lt; 3, grade IV vs III glioma, surgical resection vs biopsy, radiotherapy, temozolomide, bevacizumab, and IDH / TP53 / EGFR / TERT / PTEN / CDKN2AB / ATRX mutations predicted OS (p &lt; 0.01 for all). On multivariable analysis, ECOG ≥3 vs &lt; 3, grade IV vs III glioma, surgical resection vs biopsy, temozolomide, bevacizumab, PTEN and CDKN2AB mutations have remained to predict OS (p &lt; 0.01 for all). Conclusions: In our cohort, NGS results provided additional prognostic value, however led to change in the management for only 4% of patients with high-grade glioma.

A descriptive report of outcomes of primary mucinous ovarian cancer patients receiving either an adjuvant gynecologic or gastrointestinal chemotherapy regimen.

We described progression-free survival and overall survival in patients with primary mucinous ovarian cancer receiving adjuvant gynecologic versus gastrointestinal chemotherapy regimens. We identified all primary mucinous ovarian cancer patients receiving adjuvant gynecologic or gastrointestinal chemotherapy regimens at a single institution from 1994 to 2016. Gynecologic pathologists using strict pathologic/clinical criteria determined diagnosis. Adjuvant therapy was coded as gynecologic or gastrointestinal based on standard agents and schedules. Clinical/pathologic/treatment characteristics were recorded. Wilcoxon rank-sum test was used for continuous variables, and Fisher's exact test for categorical variables. Progression-free and overall survival were calculated using the Kaplan-Meier method, applying landmark analysis. Of 62 patients identified, 21 received adjuvant chemotherapy: 12 gynecologic, 9 gastrointestinal. Median age (in years) at diagnosis: 58 (range 25-68) gynecologic cohort, 38 (range 32-68) gastrointestinal cohort (p=0.13). Median body mass index at first post-operative visit: 25 kg/m2 (range 18-31) gynecologic cohort, 23 kg/m2 (range 18-31) gastrointestinal cohort (p=0.23). History of smoking: 6/12 (50%) gynecologic cohort, 3/9 (33%) gastrointestinal cohort (p=0.66). Stage distribution in gynecologic and gastrointestinal cohorts, respectively: stage I: 9/12 (75%) and 3/9 (33%); stage II: 2/12 (17%) and 1/9 (11%); stage III: 1/12 (8%) and 5/9 (56%) (p=0.06). Grade distribution in gynecologic and gastrointestinal cohorts, respectively: grade 1: 8/12 (67%) and 1/9 (13%); grade 2/3: 4/12 (33%) and 7/9 (88%) (p=0.03). Three-year progression-free survival: 90.9% (95% CI 50.8% to 98.7 %) gynecologic, 53.3% (95% CI 17.7% to 79.6%) gastrointestinal. Three-year overall survival: 90.9% (95% CI 50.8% to 98.7%) gynecologic, 76.2% (95% CI 33.2% to 93.5%) gastrointestinal. Ongoing international collaborative research may further define associations between chemotherapy regimens and survival.

R-CHOP without radiation in frontline management of primary mediastinal B-cell lymphoma

Prior to the introduction of rituximab, primary mediastinal B-cell lymphoma (PMBCL) had high rates of treatment failure with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP), prompting the use of consolidative mediastinal radiation or more intensive chemotherapy regimens. Cure rates improved dramatically with rituximab, but mediastinal radiation was still commonly employed with R-CHOP. We performed a retrospective review of patients treated with R-CHOP alone without radiation for PMBCL. Of 43 patients with PMBCL, 16 received R-CHOP alone. High-risk factors included 56% with bulky disease, 75% with elevated LDH, 25% with SVC syndrome, and 13% with stage IV disease. Three-year progression-free survival (PFS) and overall survival (OS) were 93% and 100% respectively. These results suggest that R-CHOP alone has a high cure rate in PMBCL while avoiding the side effects of mediastinal radiation.

No Added Benefit of Eight Versus Six Cycles of CHOP When Combined with Rituximab in Previously Untreated Diffuse Large B-Cell Lymphoma Patients: Results from the International Phase III GOYA Study

No Added Benefit of Eight Versus Six Cycles of CHOP When Combined with Rituximab in Previously Untreated Diffuse Large B-Cell Lymphoma Patients: Results from the International Phase III GOYA Study

Liver surgery prolongs the survival of patients with gastrointestinal stromal tumor liver metastasis: a retrospective study from a single center.

ObjectivesGastrointestinal stromal tumor (GIST) liver metastasis (GLM) is a special subset of advanced GIST, because its lesions are easier to define and assess. We aim to determine the role of liver metastasectomy for patients with GLM in the era of tyrosine kinase inhibitor (TKI) therapy.MethodsWe reviewed patients with metastatic GIST who received surgery or other treatments in Sun Yat-sen University Cancer Center between January 1991 and December 2017. Patients with metastases confined to the liver and with no previous metastasis to other locations were included into the study and were classified into surgical and non-surgical groups. All patients received 400 mg/d imatinib after the operation. We compared progression-free survival (PFS) and overall survival (OS) between the two groups.ResultsA total of 102 patients were included into the study. Of them, 21 (20.1%) underwent surgery for liver metastases and 81 (79.9%) received TKI therapy alone. During the operation, six patients received radiofrequency ablation for suspicious or unresectable lesions. Three-year PFS rate was 77.5% in the surgical group and 65.5% in the non-surgical group (P=0.027); 5-year OS rate was 85.7% and 59.6%, respectively (P=0.008). About 22.1% of patients had metastases of less than three in the surgical group, while the rate was 42.9% in the non-surgical group (P=0.011). Patients with metastases of less than three had longer PFS than those with three or more, with a 3-year PFS rate of 72.8% and 65.8%, respectively (P=0.019). But their difference in 5-year OS rate was not significant (91.7% vs 55.3%, P=0.08).ConclusionFollowed by continuous TKI therapy, R0 surgery significantly prolongs the survival of patients with GLM, regardless of the extent of disease or the phase of metastasis.

Influence of perioperative intraarterial selective chemotherapy on terms of recurrent ductal adenocarcinoma of the pancreatic head after pancreaticoduodenectomy

Aim.To analyze influence of perioperative intra-arterial selective chemotherapy on terms of recurrent ductal adenocarcinoma of pancreatic head after pancreaticoduodenectomy.Material and methods. 111 patients underwent combined treatment. Surgical stage included conventional pylorussparing pancreaticoduodenectomy in all groups. The main group consisted of 52 patients who received combined treatment: neoadjuvant chemoembolization with gemcitabine (400 mg/m2) and oxaliplatin (50 mg/m2), surgical treatment and 6 courses of regional chemotherapy – infusion of gemcitabine (800 mg/m2) and oxaliplatin (45 mg/m2) into celiac trunk in adjuvant mode. The control group was presented by 59 patients who underwent perioperative regional chemotherapy (neoadjuvant chemoembolization and adjuvant infusion of gemcitabine (800 mg/m2). Progression-free survival (PFS) and terms of recurrence were analyzed in all groups. In case of progression and recurrence we applied regional chemotherapy alone. Systemic chemotherapy was not used in the study.Results.Annual PFS in the main and the control groups was 80%. Three-year PFS in the main group was 37%, in the control group – 14% (p &lt; 0.01). Five-year PFS was 11% in the main group and absent in the control group. Median survival was 26 months in the main group and 22.6 months in the control group. Overall annual, 2-year and 5-year survival in main group was 80%, 57% and 15%, respectively.Conclusion.Regional intra-arterial chemotherapy decreases incidence of recurrences and improves PFS after surgical treatment of pancreatic head adenocarcinoma.Further multi-center studies are necessary to assess the effectiveness of regional chemotherapy.

Pediatric Central Nervous System Atypical Teratoid/Rhabdoid Tumor: Early and Aggressive Post-Operative Radiation Therapy Provides Better Outcome

Atypical teratoid/rhabdoid tumor (AT/RT) is a rare and highly aggressive pediatric CNS malignant tumor mainly affects infants and young children. The purpose of the study is to evaluate the possible prognostic factors and optimal management for this rare disease. Twenty-eight pediatric patients of CNS AT/RT treated with radiation therapy (RT) as part of multimodality treatment at one institution between 1996 and 2015 were retrospectively reviewed. Progression free survival (PFS), overall survival (OS), and neuro-axis failure free survival were analyzed in correlation with possible prognostic factors. The median age at diagnosis was 4.3 years old (range 0.6-19 years), with 12 patients (42.9%) less than 3 years old. Six patients (21.4%) had neuro-axis spreading at diagnosis. Radiotherapy was delayed for a longer period after surgery in patients less than 3 years old compared to older ones, with mean interval 4.9 and 1.9 months, respectively (p=0.06). Chemotherapy was given before RT initiation in 14 patients (50.0%). All of the patients ≥ 3 years old received cranio-spinal irradiation (CSI) followed by boost to tumor bed, while only 4 patients < 3 years-old(33.3%) did so (p<0.01). Mean dose to the primary tumor bed was 48.7 Gy (range 30.0-56.0 Gy), and mean CSI dose was 29.8Gy (range 24.0-36.0 Gy). Seven of 12 patients < 3 years old received high dose chemotherapy and autologous peripheral blood stem cell (PBSC) rescue. The median follow-up period was 45 months. The median PFS was 11 months and OS was 67 months. Three-year PFS was 46.4%, and OS was 60.7%. At the end of follow-up, 15 patients (53.6%) suffered from disease relapse; 13 of them had disseminating neuraxis seeding, and 11 died within one year after relapse. Interval between surgery and RT > 2 months (HR= 3.38, p=0.01) was correlated with worse PFS, while higher tumor bed RT dose (HR 0.9, p<0.01) was associated with better PFS. Overall survival was significantly worse with interval between surgery and RT > 2 months (HR=3.54, p=0.02). Cranio-spinal irradiation increased neuraxis failure free survival (HR 0.36, p= 0.05). In the group of patients < 3 years old, high dose chemotherapy followed by autologous PBSC rescue was associated with better OS compared to intravenous +/- intra-thecal chemotherapy alone (HR 0.15, p=0.04). Early and aggressive RT immediately after surgery is critical for disease control. Prognosis is extremely poor after relapse. For younger patients, high dose chemotherapy with autologous PBSC rescue provides better outcome, and may be considered as an alternative treatment to cranio-spinal irradiation.

Liver Resection for Hepatic Metastases from Soft Tissue Sarcoma: A Nationwide Study

Background: This study aims to evaluate the feasibility and safety of resection of sarcoma liver metastases, and to identify possible prognostic factors for long-term survival. Methods: All patients who underwent resection of liver metastases of sarcoma in the Netherlands from 1998 to 2014 were included. Study data was retrospectively collected from patient files. Survival rates were calculated using Kaplan-Meier survival analysis. Results: Some 38 patients treated in 16 hospitals were included (15 male, 23 female). The median age was 57 years (37–80 years). The most common histological subtype was leiomyosarcoma (63%). The predominant site of primary tumour was the abdomen (59%). R0 resection was achieved in 16 patients. Mortality was 3 and 16% of included patients had 1 or more complications. The median follow-up period was 18 months (range 1–161). After liver resection, 1-, 3-, and 5-year survival were 88, 54, and 42% respectively. Median overall survival was 46 months (1–161 months). One- and three-year progression-free survival (PFS) after liver resection were 54 and 19% respectively. Median PFS was 16 months (1–61 months). Conclusions: Liver surgery for sarcoma metastases is safe and leads to a relatively good survival. The choice for surgical treatment should always be discussed in a multidisciplinary sarcoma and liver team.

Clinical characteristics and survival analysis of de novo grade 3 or transformed follicular lymphoma patients

目的探讨初治3级或伴有大B细胞转化滤泡淋巴瘤（FL）患者的临床特征及预后。方法收集2009年1月至2017年9月在北京大学肿瘤医院诊断治疗的52例FL患者资料，对患者的基本临床特征、生存及预后因素进行统计学分析。结果①52例患者中，男女各26例，其中3A级28例，3B级13例，伴大B细胞转化11例。②整组患者的3年无进展生存（PFS）率为56.0%，3年总生存（OS）率为80.6%。IPI评分0~1分者较2~3分者的3年PFS率（80.3%对20.1%，t=18.902，P<0.001）和OS率（95.7%对57.0%，t=10.406，P<0.001）高；FLIPI 1评分低、中、高危组患者的3年PFS率分别为94.1%、37.2%、25.2%（P=0.002），3年OS率分别为100%、76.0%、59.8%（P=0.020），FLIPI 2评分低、中、高危组患者的3年PFS率分别为68.4%、0、0（P=0.001），3年OS率分别为87.5%、76.2%、0（P=0.003），差异均有统计学意义。③多因素分析显示，IPI评分≥2分是影响患者PFS（HR=3.536，P=0.015）和OS（HR=15.713，P=0.015）的不良预后因素；FLIPI 2评分与患者OS（以≥3分为参照，0~1分：HR=0.078，P=0.007；2分：HR=0.080，P=0.022）显著相关。结论以现有治疗手段，初治高级别FL和伴大B细胞转化FL有可能治愈，IPI评分仍可以预测该组患者预后。

Nasopharyngeal carcinoma outcome with induction chemotherapy followed by concurrent chemoradiotherapy

Treatment of Nasopharyngeal Carcinoma (NPC) has been based on the Intergroup 0999 trial with chemoradiation (CRT) and consolidation chemotherapy (CT). While effective, toxicities are significant. As a result, many oncologists use induction chemotherapy (IC) followed by CRT, citing better tolerance with anecdotally no worse outcome. We reviewed 95 NPC patients treated between 2005 and 2015 at MDACC with IC followed by CRT. Median age was 49 years. Fifty-seven were T3/T4 and 62 were N2-3. The most common IC regimen was a platinum-taxane doublet (N = 72). 83 patients completed IC. Grade 3–4 toxicities with IC occurred in 10 patients. There were 15 primary site complete responses (CR), 68 partial responses (PR),6 stable disease (SD), and 2 progressed. There were 10 nodal CR, 73 PR, 4 SD, and 3 progressed. 92 patients received RT, 74 with CRT. At completion of treatment, there were 81 CR and 8 PR patients.Post radiation toxicities included mucositis and skin rash (37), oto- toxicity (25), PEG placement (12), and osteonecrosis (2). Three-year progression free survival (PFS) and distant metastasis free survival (DMFS) were 77.3% and 78%. CRT for advanced NPC is standard, but IC remains controversial. Early trials failed to show a benefit but used older chemotherapy and pre-intensity modulated radiation therapy (IMRT) methods. Modern trials with platinum-taxane regimens and IMRT have shown reasonable PFS and OS results with acceptable toxicity. This retrospective review of IC followed by CRT showed acceptable toxicity and good response and survival outcomes. This approach has, for many oncologists, become a standard.

Prognostic significance of (18)F-fluorodeoxyglucose positron emission tomography in patients with diffuse large B cell lymphoma undergoing autologous stem cell transplantation

目的探讨18F-FDG PET-CT评估在接受auto-HSCT的弥漫大B细胞淋巴瘤（DLBCL）患者中的预后价值。方法回顾性分析2010年11月至2014年12月在北京大学肿瘤医院接受auto-HSCT的48例DLBCL患者资料，所有患者移植前或者移植后行PET-CT检查，结合患者基本临床特征及生存进行相关性分析。结果①48例患者中，男27例，女21例，中位年龄为43（17~59）岁。②移植前PET-CT评估阴性和阳性患者的3年无进展生存（PFS）率分别为87.1%和53.3%（χ2=7.02，P=0.019），3年总生存（OS）率分别为90.3%和60.0%（χ2=6.51，P=0.022）；移植后两组患者的3年PFS率分别为94.1%和30.0%（χ2=22.75，P=0.001），3年OS率分别为97.1%和40.0%（χ2=21.09，P=0.002）。③多因素分析结果显示，移植后PET-CT评估阳性是影响患者PFS（HR=13.176，P=0.005）和OS（HR=20.221，P=0.007）的预后不良因素；移植前治疗方案数与PFS相关（HR=10.039，P=0.040）。④Harrell's C值显示移植后PET-CT评估与移植前治疗方案数联合使用预测PFS的价值优于单独使用（联合使用、移植前治疗方案数、移植后PET-CT评估的Harrell's C值分别为0.976、0.869、0.927）；移植后PET-CT与ECOG体力状态评分联合使用能更好预测OS（联合使用、ECOG体力状态评分、移植后PET-CT评估的Harrell's C值分别为0.973、0.711、0.919）。结论移植后PET-CT评估在接受auto-HSCT的DLBCL患者中有重要预后作用，移植后PET-CT评估联合移植前治疗方案数以及ECOG体力状态评分可能能够更好地预测患者预后。

Prognosis of multi-level N2-positive non-small cell lung cancer according to lymph node staging using endobronchial ultrasound-transbronchial biopsy.

BackgroundThe optimal treatment for stage IIIA‐N2 non‐small cell lung cancer (NSCLC) remains controversial, and multidisciplinary team approaches are needed. Downstaging after induction therapy is a good prognostic factor in surgical patients; however, re‐evaluation of nodal status before surgery is challenging. The aim of this study was to evaluate the prognosis of patients with multi‐level N2 NSCLC who received surgery or chemoradiation therapy (CRT) according to restaging using endobronchial ultrasound‐transbronchial aspiration (EBUS‐TBNA).MethodsThis was a single center, prospective study that included 16 patients with biopsy‐proven multi‐level N2 disease on initial EBUS‐TBNA that was restaged using EBUS‐TBNA after induction therapy. Cases downstaged after rebiopsy were treated surgically. Three‐year progression‐free survival (PFS) and locoregional PFS were determined using Kaplan–Meier analysis.ResultsOf the 16 patients (median age 58 years, male 63%), eight had persistent N2 disease and eight showed N2 clearance on restaging using EBUS‐TBNA. Ten patients underwent surgery, including two patients without N2 clearance. Recurrence and locoregional recurrence occurred in eight and five patients, respectively. The three‐year PFS was longer in patients with N2 clearance than in those with N2 persistent disease (57.1% vs. 37.5%). Patients with N2 clearance also had longer three‐year locoregional PFS than those with N2 persistent disease (71.4% vs. 62.5%).ConclusionsEBUS‐TBNA could be an effective diagnostic method for restaging in multi‐level N2 NSCLC patients after induction CRT. As this was a pilot study, further large‐scale randomized studies are needed.

Results of a multi-institutional, randomized, non-inferiority, phase III trial of accelerated fractionation versus standard fractionation in radiation therapy for T1-2N0M0 glottic cancer: Japan Clinical Oncology Group Study (JCOG0701)

BackgroundWe assessed the non-inferiority of accelerated fractionation (AF) (2.4Gy/fraction) compared with standard fractionation (SF) (2Gy/fraction) regarding progression-free survival (PFS) in patients with T1-2N0M0 glottic cancer (GC). Patients and methodsIn this multi-institutional, randomized, phase III trial, patients were enrolled from 32 Japanese institutions. Key inclusion criteria were GC T1-2N0M0, age 20–80, Eastern Cooperative Oncology Group performance status of 0–1, and adequate organ function. Patients were randomly assigned to receive either SF of 66–70Gy (33–35 fractions), or AF of 60–64.8Gy (25–27 fractions). The primary end point was the proportion of 3-year PFS. The planned sample size was 360 with a non-inferiority margin of 5%. ResultsBetween 2007 and 2013, 370 patients were randomized (184/186 to SF/AF). Three-year PFS was 79.9%(95% confidence interval [CI] 73.4–85.4) for SF and 81.7% (95% CI 75.4–87.0) for AF (difference 1.8%, 91% CI−5.1% to 8.8%; one-sided P=0.047>0.045). The cumulative incidences of local failure at 3years for SF/AF were 15.9%/10.3%. No significant difference was observed in 3-year overall survival (OS) between SF and AF. Grade 3 or 4 acute and late toxicities developed in 22 (12.4%)/21 (11.5%) and 2 (1.1%)/1 (0.5%) in the SF/AF arms. ConclusionAlthough the non-inferiority of AF was not confirmed statistically, the similar efficacy and toxicity of AF compared with SF, as well as the practical convenience of its fewer treatment sessions, suggest the potential of AF as a treatment option for early GC. Clinical trials registrationUMIN Clinical Trial Registry, number UMIN000000819.

Predictive value of 18F-FDG PET/CT before or after autologous hematopoietic stem cell transplantation for the clinical outcome of patients with non-Hodgkin′s lymphoma

Objective To evaluate the predictive value of 18F-fluorodeoxyglucose (FDG) PET/CT before or after autologous hematopoietic stem cell transplantation (Auto-HSCT) in patients with non-Hodgkin′s lymphoma (NHL). Methods Fifty-eight NHL patients who underwent PET/CT scan before or after Auto-HSCT were retrospectively analyzed. Between June 2007 and May 2016, 40 patients (32 males, 8 females; median age 39 years) underwent 18F-FDG PET/CT pre-transplantation, and 34 patients (23 males, 11 females; median age 34 years) underwent 18F-FDG PET/CT post-transplantation. There were 16 patients underwent both pre- and post-transplantation imaging. PET/CT results were categorized as positive or negative according to the standard response criteria. The predictive value of PET/CT was evaluated with progression-free survival (PFS) and overall survival (OS) using Kaplan-Meier survival analysis and log-rank test. Three-year PFS and OS of different groups were compared with Fisher exact test. Results (1)18F-FDG PET/CT before Auto-HSCT: PFS of patients in PET/CT negative group (n=27) and positive group (n=13) were significantly different (χ2=4.187, P 0.05). (2)18F-FDG PET/CT after Auto-HSCT: PFS and OS of patients in PET/CT negative group (n=18) and positive group (n=16) were significantly different (χ2 values: 15.430, 7.726, both P<0.01). The 3-year PFS and OS of the 2 groups were 8/10 vs 2/12(P=0.005) and 8/10 vs 4/12 (P=0.038), respectively. Conclusion 18F-FDG PET/CT before or after Auto-HSCT could provide prognostic information for NHL patients. Key words: Lymphoma, non-Hodgkin; Hematopoietic stem cell transplantation; Prognosis; Positron-emission tomography; Tomography, X-ray computed; Deoxyglucose