Results of spot-scanning proton radiation therapy for chordoma and chondrosarcoma of the skull base: the Paul Scherrer Institut experience

PURPOSE: To assess the clinical results of spot scanning proton beam radiation therapy (PT) in the treatment of skull base chordomas and low-grade chondrosarcomas (CS). METHODS AND MATERIALS: Between October 1998 and October 2003, 29 patients (median age, 39 years) with chordomas (n = 18) and CS (n = 11) were treated at the Paul Scherrer Institut (PSI) with protons using the main 510-MeV cyclotron. Tumor conformal application of proton beams was realized by spot scanning technology. The median chordoma and CS dose was 74 and 68 cobalt Gy equivalent, respectively (cobalt Gy equivalent = proton Gy x 1.1). Median gross tumor volumes (GTV) were 16.4 mL (range, 1.8-48.1 mL) and 15.2 mL (range, 2.3-57.3 mL) for chordoma and CS, respectively. Late toxicity was assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE, v3.0) grading system. The median follow-up time was 29 months (range, 6-68 months). RESULTS: Actuarial 3-year local control rates were 87.5% and 100% for chordoma and CS, respectively. We observed one surgical pathway and one marginal failure in patients with chordomas. No regional failure or distant metastasis was observed. At 3 years, actuarial PFS and OS for the entire cohort was 90% and 93.8%, respectively. Actuarial 3-year complication-free survival was 82.2%. Radiation-induced pituitary dysfunction was observed in 4 (14%) patients (CTCAE Grade 2). No patient presented with post-PT brainstem or optic pathways necrosis or dysfunction. In univariate analysis, age < or =40 years at the time of PT affected favorably on PFS (p = 0.09). CONCLUSION: Spot-scanning PT offers high tumor control rates of skull base chordoma and CS. These results compare favorably to other combined proton-photon or carbon ion irradiation series. Observed toxicity was acceptable. Younger age (< or =40 years) was a favorable prognostic factor of PFS. These preliminary results are encouraging but should be confirmed during a longer follow-up.     

Intracranial low-grade gliomas in adults: 30-year experience with long-term follow-up at Mayo Clinic

The purpose of this study was to evaluate long-term survival in patients with nonpilocytic low-grade gliomas (LGGs). Records of 314 adult patients with nonpilocytic LGGs diagnosed between 1960 and 1992 at the Mayo Clinic, Rochester, Minnesota, were retrospectively reviewed. The Kaplan-Meier method estimated progression-free survival (PFS) and overall survival (OS). Median age at diagnosis was 36 years. Median follow-up was 13.6 years. Operative pathology revealed pure astrocytoma in 181 patients (58%), oligoastrocytoma in 99 (31%), and oligodendroglioma in 34 (11%). Gross total resection (GTR) was achieved in 41 patients (13%), radical subtotal resection (rSTR) in 33 (11%), subtotal resection in 130 (41%), and biopsy only in 110 (35%). Median OS was 6.9 years (range, 1 month–38.5 years). Adverse prognostic factors for OS identified by multivariate analysis were tumor size 5 cm or larger, pure astrocytoma histology, Kernohan grade 2, undergoing less than rSTR, and presentation with sensory motor symptoms. Statistically significant adverse prognostic factors for PFS by multivariate analysis were only tumor size 5 cm or larger and undergoing less than rSTR. In patients who underwent less than rSTR, radiotherapy (RT) was associated with improved OS and PFS. A substantial proportion of patients have a good long-term prognosis after GTR and rSTR, with nearly half of patients free of recurrence 10 years after diagnosis. Postoperative RT was associated with improved OS and PFS and is recommended for patients after subtotal resection or biopsy.     

Postoperative spot-scanning proton radiation therapy for chordoma and chondrosarcoma in children and adolescents: initial experience at paul scherrer institute

PURPOSE: To evaluate postoperative spot-scanning proton radiation therapy (PT) and intensity-modulated PT (IMPT) for chordoma and chondrosarcoma in pediatric patients. METHODS AND MATERIALS: Between 2000 and 2005, 10 patients (six male patients, four female patients; six chordomas, four chondrosarcomas), aged 10-20 years (median, 16 years), were treated at our institute. Tumor sites were in the brain (one case), skull base (five cases), cervical (three cases), and lumbar spine (one case). Three children had complete resections. In seven children, resection was incomplete, leaving residual tumor behind (range, 2.3-46.3 mL). PT was delivered using spot scanning, with (three patients) or without (seven patients) IMPT. Total dose was 74.0 cobalt Gray equivalents (CGE) for chordoma, and 63.2-68.0 CGE for chondrosarcoma (median, 66.0), depending on histopathological grading and whether the patient had concurrent chemotherapy. RESULTS: Median follow-up time was 36 months (range, 8-77 months). Radiation treatment was well tolerated. All patients remained failure-free at their last follow-up. Late adverse events were reported in three patients and were mild (neurosensory in one patient; alopecia and hypoaccusis in one patient) to moderate (one patient, Grade 2 pituitary insufficiency). CONCLUSIONS: Postoperative spot-scanning PT, delivered in combination with and without IMPT, for chordoma and chondrosarcoma in children and adolescents was tolerated without unacceptable adverse event and initial outcome is perfectly satisfactory in this small cohort. Longer follow-up time and larger cohort are needed to more fully assess tumor control, adverse events, as well as functional and cosmetic outcome.     

Role of exclusive chemotherapy as first line treatment in oligodendroglioma

PURPOSE: The optimal therapy of oligodendrogliomas remains uncertain. Although chemosensitive, these tumors are not chemocurable. We investigated whether chemotherapy delays the need for radiation therapy (RT) without decreasing length and quality of survival. METHODS AND MATERIALS: Among 89 patients treated for oligodendrogliomas at the Centre Léon Bérard of Lyon from 1982 to 1999, 59 patients fitted inclusion criteria, having had centrally reviewed pure oligodendroglioma requiring treatment. According to the WHO's classification 35 patients had Grade III and 24, Grade II oligodendrogliomas. RESULTS: According to the intent to treat, patients were retrospectively classified in three groups as exclusive RT (Group 1), radio-chemotherapy (Group 2), or exclusive chemotherapy (Group 3). Median progression-free survival (PFS): was 47 months [95% confidence interval (CI) 39-56], and median overall survival (OS) was 109 months (95% CI 83-134). In univariate analysis, PFS was correlated with frontal location and WHO classification; OS was correlated with frontal location and Post-operative Karnosky performans status both appearing as independent prognostic factors for OS in multivariate analysis. There was no significant difference between the treatment groups with regard to PFS (P = 0.82) and OS (P = 0.64). In the group of patients treated with exclusive chemotherapy the 5-year PFS and OS rates were 44 and 71%, respectively. CONCLUSION: Front-line exclusive chemotherapy results in prolonged OS in patients with confirmed pure oligodendroglioma. Whether this strategy improves quality of life remains debatable.     

Phase II clinical trial of pazopanib for patients with unresectable or metastatic malignant peripheral nerve sheath tumors

Malignant peripheral nerve sheath tumor (MPNST) often does not respond well to chemotherapy and develops against a background of NF1. The purpose of our study was to examine the efficacy of pazopanib against MPNST. Our study was designed as a physician‐initiated phase II clinical trial in patients with advanced MPNST. Patients were registered from 11 large hospitals. The primary endpoint was set to clarify the clinical benefit rate (CBR) at 12 weeks according to response evaluation criteria in solid tumors (RECIST). Progression‐free survival (PFS), overall survival (OS) and the CBR based on modified Choi evaluation at week 12 were set as secondary endpoints along with treatment‐related safety. The study enrolled 12 patients. Median age was 49 years. Seven had Grade 2 and five Grade 3 according to the FNCLCC evaluation. Median follow‐up period was 10.6 months. CBR at 12 weeks was both 50.0% (RECIST and Choi). The median PFS was 5.4 months for both RECIST and Choi, and the median OS was 10.6 months. Of special interest, the median PFS was 2.9 months for patients with FNCLCC Grade 2 and 10.2 months for Grade 3 (both RECIST and Choi). Grade 4 adverse events of neutropenia and lipase elevation were noted in one patient each. The results of this pazopanib therapy were generally better than those of any of the other single molecular targeted therapies reported previously. Although accumulation of more cases remains necessary, we conclude pazopanib treatment for MPNST to be a safe and promising treatment after doxorubicin‐based chemotherapy.     

Longitudinal experience with WHO Grade III (anaplastic) meningiomas at a single institution

To retrospectively analyze and assess the outcomes and prognostic factors in patients with anaplastic meningioma (AM) (WHO Grade III). Clinical data and outcome [overall (OS) and progression-free (PFS) survival] from 18 patients with Grade III meningioma (AM, based on World Health Organization 2016 definition) initially treated between March 2000 and June 2015 were analyzed. Eleven patients (61%) were male, median age at diagnosis was 63 (range 48–86), and 55% (10/18 patients) had good performance status (KPS?≥?80). Eight patients (45%) had lower grade disease (Grade I—n?=?2; Grade II—n?=?6) prior to being upgraded to AM. Ten patients had fractionated radiation after primary surgery, eight patients had salvage fractionated RT, stereotactic radiosurgery (SRS) boost along with primary RT in 1 patient, and salvage SRS to 18 separate areas in 14 patients. Salvage chemotherapy was mainly considered in third or fourth recurrences. 13 (72%) patients recurred and 10 (56%) have died. Median PFS was 14.5 months (95% CI 6.9–22.2). The 5-year survival rate was 40?±?15% and median OS was 55.8 months (95% CI 27.7–80.3). Of all factors examined, only Karnofsky performance status (KPS) affected outcome (PFS p?=?0.0003; OS p?=?0.0003). With median OS of 55 months (4.6 years) our results are consistent with existing reports of the poor outcomes for AM patients. From the available data, surgical resection followed by RT and salvage radiosurgery and/or chemotherapy can lead to extended survival; however the benefit may decrease with successive treatments.     

Dose-escalation with proton/photon irradiation for Daumas-Duport lower-grade glioma: results of an institutional phase I/II trial

PURPOSE: The role of dose escalation with proton/photon radiotherapy in lower-grade gliomas was assessed in a prospective Phase I/II trial. We report the results in terms of local control, toxicity, and survival. MATERIALS AND METHODS: Twenty patients with Grade 2/4 (n = 7) and Grade 3/4 (n = 13) gliomas according to the Daumas-Duport classification were treated on a prospective institutional protocol at Massachusetts General Hospital/Harvard Cyclotron Laboratory between 1993 and 1996. Doses prescribed to the target volumes were 68.2 cobalt Gray equivalent (CGE, 1 proton Gray = 1.1 CGE) to gross tumor in Grade 2 lesions and 79.7 CGE in Grade 3 lesions. Fractionation was conventional, with 1.8 to 1.92 CGE once per day. Eligibility criteria included age between 18 and 70 years, biopsy-proven Daumas-Duport Grade 2/4 or 3/4 malignant glioma, Karnofsky performance score of 70 or greater, and supratentorial tumor. Median age of the patient population at diagnosis was 35.9 years (range 19-49). Ten tumors were mixed gliomas, one an oligodendroglioma. RESULTS: Five patients underwent biopsy, 12 a subtotal resection, and 3 a gross total resection. Median interval from surgery to first radiation treatment was 2.9 months. Actuarial 5-year survival rate for Grade 2 lesions was 71% as calculated from diagnosis (median survival not yet reached); actuarial 5-year survival for Grade 3 lesions was 23% (median 29 months). Median follow-up is 61 months and 55 months for 4 patients alive with Grade 2 and 3 patients alive with Grade 3 lesions, respectively. Three patients with Grade 2 lesions died from tumor recurrence, whereas 2 of the 4 survivors have evidence of radiation necrosis. Eight of 10 patients who have died with Grade 3 lesions died from tumor recurrence, 1 from pulmonary embolus, and 1 most likely from radiation necrosis. One of 3 survivors in this group has evidence of radiation necrosis. CONCLUSION: Tumor recurrence was neither prevented nor noticeably delayed in our patients relative to published series on photon irradiation. Dose escalation using this fractionation scheme and total dose delivered failed to improve outcome for patients with Grade 2 and 3 gliomas.     

Survival analysis in patients with newly diagnosed primary glioblastoma multiforme using pre- and post-treatment peritumoral perfusion imaging parameters

The objective of this study was to evaluate if peritumoral (PT) perfusion parameters obtained from dynamic susceptibility weighted contrast enhanced perfusion MRI can predict overall survival (OS) and progression free survival (PFS) in patients with newly diagnosed glioblastoma multiforme (GBM). Twenty-eight newly diagnosed GBM patients, who were treated with resection followed by concurrent chemoradiation and adjuvant chemotherapy, were included in this study. Evaluated perfusion parameters were pre- and post-treatment PT relative cerebral blood volume (rCBV) and relative cerebral blood flow (rCBF). Proportional hazard analysis was used to assess the relationship OS, PFS and perfusion parameters. Kaplan–Meier survival estimates and log-rank test were used to characterize and compare the patient groups with high and low perfusion parameter values in terms of OS and PFS. Pretreatment PT rCBV and rCBF were not associated with OS and PFS whereas there was statistically significant association of both posttreatment PT rCBV and rCBF with OS and posttreatment rCBV with PFS (association of PFS and posttreatment rCBF was not statistically significant). Neither the Kaplan–Meier survival estimates nor the log-rank test demonstrated any differences in OS between high and low pretreatment PT rCBV values and rCBF values; however, high and low post-treatment PT rCBV and rCBF values did demonstrate statistically significant difference in OS and PFS. Our study found posttreatment, not pretreatment, PT perfusion parameters can be used to predict OS and PFS in patients with newly diagnosed GBM.     

85例颅外转移性乳腺癌放疗疗效观察及预后分析

目的:观察颅外转移性乳腺癌的放疗疗效,探讨全病变放疗意义及预后相关因素。方法:回顾性分析2014—2019年间接受放疗的85例颅外转移性乳腺癌患者的临床资料,其中全病变放疗36例,非全病变放疗49例。采用 Kaplan- Meier法计算生存率并 log- rank检验和...     

Central nervous system metastasis from epithelial ovarian cancer- predictors of outcome

Management of central nervous system (CNS) metastases from epithelial ovarian cancer (EOC) is an unmet need. We analyzed data on 41 such patients to evaluate predictors of outcome. Between January, 2010 and December 2020, among 1028 patients with EOC treated at our institute 41 (3.98%) developed CNS metastasis. Median age of patients was 48 years, ranging from 22 to 75 years. Primary outcome measure was progression free survival (PFS). Overall survival (OS), and analysis of prognostic factors were secondary outcome measures. An intention to treat analysis was done. We also performed review the literature (n=2253) as regards to clinicopathological and radiological features, treatment received, survival outcomes and prognostic factors. Median time from diagnosis of EOC to CNS metastasis was 27 months (range: 0 to 101 months). 33(80.5%) patients had FIGO stage III-IV at baseline and serous carcinoma (75.6%) was common pathology subtype. Thirteen (31.7%) patients had isolated CNS metastasis and 28 (68.3%) had intra-abdominal disease in addition. Nineteen (46.3%) patients achieved complete response post treatment with surgery, radiation and chemotherapy. Median PFS and OS from the time of CNS metastasis is 12 (range:1 to 51) months and 33 (range: 1 to 71) months, respectively. Absence of extracranial disease and lower serum CA-125 at diagnosis of CNS metastasis were predictive of superior PFS and OS on multivariate analysis. CNS metastasis is a late event in EOC, post multiple lines of treatment. Patients with disease limited to brain and treated with surgical resection and chemoradiation have best outcome.     

Prolonged survival for patients with newly diagnosed, inoperable glioblastoma with 3-times daily ultrafractionated radiation therapy

Ultrafractionation of radiation therapy is a novel regimen consisting of irradiating tumors several times daily, delivering low doses (<0.75 Gy) at which hyperradiosensitivity occurs. We recently demonstrated the high efficiency of ultrafractionated radiotherapy (RT) on glioma xenografts and report here on a phase II clinical trial to determine the safety, tolerability, and efficacy of an ultrafractionation regimen in patients with newly and inoperable glioblastoma (GBM). Thirty-one patients with histologically proven, newly diagnosed, and unresectable supratentorial GBM (WHO grade IV) were enrolled. Three daily doses of 0.75 Gy were delivered at least 4 hours apart, 5 days per week over 6–7 consecutive weeks (90 fractions for a total of 67.5 Gy). Conformal irradiation included the tumor bulk with a margin of 2.5 cm. The primary end points were safety, toxicity, and tolerability, and the secondary end points were overall survival (OS) and progression-free survival (PFS). Multivariate analysis was used to compare the OS and PFS with the EORTC-NCIC trial 26981-22981/CE.3 of RT alone vs radiation therapy and temozolomide (TMZ). The ultrafractionation radiation regimen was safe and well tolerated. No acute Grade III and/or IV CNS toxicity was observed. Median PFS and OS from initial diagnosis were 5.1 and 9.5 months, respectively. When comparing with the EORTC/NCIC trial, in both PFS and OS multivariate analysis, ultrafractionation showed superiority over RT alone, but not over RT and TMZ. The ultrafractionation regimen is safe and may prolong the survival of patients with GBM. Further investigation is warranted and a trial associating ultra-fractionation and TMZ is ongoing.     

The role of up-front radiation therapy for incompletely resected pediatric WHO grade II low-grade gliomas

The purpose of this study was to assess the impact of early radiation therapy and extent of surgical resection on progression-free survival (PFS) and overall survival (OS) in children with WHO grade II low-grade gliomas (LGGs). We conducted a historical cohort study of 90 patients, ages 21 or younger, diagnosed with WHO grade II LGGs between 1970 and 1995. Median follow-up for surviving patients was 9.4 years (range, 0.5-22.6 years). Tests for variables correlating with OS and PFS were conducted by using log-rank tests and Cox proportional hazards models. Eleven patients underwent gross total resections (GTRs), 43 had subtotal resections, and 34 underwent biopsy only at diagnosis. Two patients underwent biopsy at time of recurrence. Of the 90 patients, 52 received radiation as part of their initial therapy following diagnosis (early-RT group). The overall five-year PFS and OS rates +/- SE were 56% +/- 5% and 90% +/- 3%, respectively. Ten-year PFS and OS rates were 42% +/- 6% and 81% +/- 5%, respectively. For patients older than three years and without GTRs, administration of early radiation did not appear to influence PFS or OS (P = 0.98 and P = 0.40, respectively; log-rank test). This was confirmed by multivariate analyses (P = 0.95 and P = 0.33 for PFS and OS, respectively). Of the 11 patients with GTRs, disease progressed in only two, and all were alive with no evidence of disease at last follow-up. Patients who underwent GTRs had significantly longer PFS (P = 0.02), but did not have significantly improved OS. Excellent long-term survival rates were achieved for children with WHO grade II LGGs. We were unable to demonstrate a benefit for administering radiation as part of initial treatment. An outcome benefit was seen with greater extent of resection.     

99例结外NK/T细胞淋巴瘤预后分析

背景与目的：结外NK/T细胞淋巴瘤的临床及预后存在明显的异质性,以早期病变为主,常见原发灶局部外侵,早期患者放疗为主要治疗手段。本研究旨在分析早期结外NK/T细胞淋巴瘤患者的临床特征、治疗方案、生存预后及可能影响预后的相关因素。方法：收集河北医科大学第四医院2010年1月—2015年12月病理证实的早期NK/T细胞淋巴瘤患者99例,发病平均年龄45.5岁（6~76岁）,男女发病比例2.1∶1;56.6%患者伴有B症状;单纯放疗7例,单纯化疗29例,放化综合治疗63例;中位放疗剂量52 Gy（34~60 Gy）,含左旋门冬酰胺酶或培门冬酶化疗患者73例,不含19例,中位化疗周期为6个（1~12个）。结果：全组患者中位生存时间59.9个月,中位局控时间73.5个月。全组患者1、2和5年总生存率分别为76.8%、68.8%和61.4%;1、2和5年局控率分别为84.5%、81.6%和78.3%;1、2和5年无远处失败生存率分别为83.4%、83.4%和76.8%。单纯放疗或放化疗与单纯化疗比较,5年总生存率为66.0%和47.3%（χ²=4.782,P=0.029）,5年局控率为85.8%和58.7%（χ²=5.949,P=0.015）。不伴原发肿瘤侵犯（primary tumor invasion,PTI）患者与伴有PTI患者比较,5年总生存率为71.5%和55.5%（χ²=4.950,P=0.026）;5年局控率为81.5%和72.0%（χ²=0.983,P=0.321）。全组近期疗效评价达CR者62例（62.6%）,治疗有效率83.8%,疾病控制率85.8%。评价CR患者与非CR患者5年生存率为84.1%和27.6%（χ²=31.566,P=0.000）;5年局控率为92.2%和52.4%（χ²=18.417,P=0.000）。结论：早期结外NK/T细胞淋巴瘤患者单放或放化综合治疗比单纯化疗疗效好,与生存有关的独立预后因素有Ann Arbor分期和乳酸脱氢酶（lactate dehydrogenase,LDH）,与局控有关的独立预后因素仅有LDH。     

局限期小细胞肺癌加速超分割放疗同步EP方案化疗的剂量递增I期研究

背景与目的加速超分割放疗（每日两次方案）联合EP方案同步化疗是美国国立综合癌症网络（Na-tional Comprehensive Cancer Network, NCCN）指南推荐的局限期小细胞肺癌的标准治疗方式,但国人对EP方案标准化疗剂量耐受性尚不明确。本研究旨在探讨局限期小细胞肺癌同步放化疗EP方案的最大耐受剂量。方法研究纳入病理证实的局限期小细胞肺癌患者,进行加速超分割放疗同步EP方案（依托泊苷+顺铂）化疗,放疗处方剂量为45 Gy/30 f,1.5 Gy/f,每日两次,同一日两次放疗间隔时间≥6 h,5天/周,共3周完成。化疗方案采用依托泊苷联合顺铂,每21天为1周期,具体依托泊苷100 mg/m2,d1-d3,顺铂采用剂量递增的方式（第1组为70 mg/m2 d1,第2组为75 mg/m2 d1）。主要观察指标为治疗期间的血液学毒性。次要观察指标为非血液学毒性和1年总生存期（overall sur-vival, OS）、无进展生存期（progression free survival, PFS）。根据不良事件常用术语评定标准（Common Terminology Criteria for Adverse Events, NCI-CTCAE）4.0,最大耐受剂量设定为6例患者中不超过1例患者出现剂量限制毒性（4级血液学毒性）的剂量,同时下一剂量组6例患者至少2例出现剂量限制性毒性。结果研究共纳入20例局限期小细胞肺癌患者,平均年龄49.50（30-68）岁。第1组入组6例患者,1例患者出现4度中性粒细胞减少;后第2组入组14例患者,1例患者出现4度中性粒细胞减少。其中,第1组有4例患者出现≥3度血液学毒性,1例患者出现3度以上放射性食管炎;第2组有10例患者出现≥3度血液学毒性,无患者出现3度以上放射性食管炎。中位随访9.0个月（3.2个月-36.2个月）,1年OS、PFS分别为91%、62%。结论局限期小细胞肺癌患者采用加速超分割放疗联合EP方案化疗将顺铂剂量递增至75 mg/m2是安全的,其有效性还需要进一步扩大样本量和随访更长的时间来证实。     

Phase II study of stereotactic body radiotherapy to primary tumor and metastatic locations in oligometastatic nonsmall-cell lung cancer patients

BackgroundStereotactic body radiotherapy (SBRT) has emerged as a treatment modality in patients presenting with oligometastatic nonsmall-cell lung cancer (NSCLC). SBRT is used as a local consolidative treatment to metastatic disease sites. The majority of patients included in SBRT trials for oligometastatic NSCLC have controlled primary tumors and brain metastases.Patients and methodsOligometastatic NSCLC patients with ≤5 metastatic lesions were included in a prospective phase II trial to evaluate efficacy and toxicity of SBRT to all disease sites, primary tumor and metastatic locations. SBRT to a dose of 50 Gy in 10 fractions was delivered. Positron emission tomography–computed tomography (PET-CT) was carried out at baseline and 3 months after SBRT to evaluate the metabolic response rate according to PET Response Criteria in Solid Tumors (PERCIST). The progression-free survival (PFS) and overall survival (OS) were calculated using Kaplan–Meier method from start of chemotherapy or radiotherapy. Side-effects were scored using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 3.0.ResultsTwenty-six patients received SBRT after induction chemotherapy (n = 17) or as a primary treatment (n = 9). Median follow-up was 16.4 months. Overall metabolic response rate was 60% with seven patients (30%) achieving a complete metabolic remission and 7 (30%) a partial metabolic response. Any acute grade 2 toxicity was observed in four patients (15%) and grade 3 pulmonary toxicity in two patients (8%). Median PFS and OS were 11.2 and 23 months. The 1-year PFS and 1-year OS rate were 45% and 67%, respectively.ConclusionSBRT to all disease sites, primary tumor and metastatic locations, in oligometastatic NSCLC patients produced an acceptable median PFS of 11.2 months.     

CHOP或CHOP样方案一线治疗晚期血管免疫母细胞型T细胞淋巴瘤效果观察

目的 分析CHOP或CHOP样方案一线治疗血管免疫母细胞型T细胞淋巴瘤(AITL)的效果.方法 回顾性分析2006年8月至2014年2月收治的29例应用CHOP或CHOP样方案一线治疗的晚期AITL患者的临床资料,总结其临床特征,分析疗效及其预后因素.结果 患者中位发病年龄为59岁,全部为Ⅲ～Ⅳ期,17例(58.6％)伴B症状,26例(89.7％)IPI评分≥2分,20例(69.0％)起病时乳酸脱氢酶升高,9例(31.0％)出现≥2个结外器官受侵.中位随访20个月,总有效率为69.0％(20/29),其中17.2％(5/29)的患者初治达完全缓解或未确定完全缓解,51.7％(15/29)达部分缓解,20.7％(6/29)出现疾病进展,10.3％(3/29)稳定.中位无进展生存(PFS)期为6个月.1、2年PFS率分别为39.0％、20.0％.1、2、5年总生存(OS)率分别为76.8％、53.4％和17.1％.治疗有效患者PFS长于无效患者(P＜ 0.001),有效与无效患者OS差异无统计学意义(P＞0.05).结论 CHOP或CHOP样方案一线治疗AITL的总体疗效不满意,有待进一步探索新的治疗方法.     

Retrospective analysis of seventy-one patients with neuroendocrine tumor and review of the literature

Neuroendocrine tumors (NET) are rare, but their incidence is gradually increasing. In this study, demographical and tumor characteristics, treatment modalities, responses, and survival rates were evaluated in the patients with NET. Seventy-one patients with NET from 3 tertiary care centers evaluated retrospectively. Overall survival (OS), progression-free survival (PFS), and disease-free survival rates were estimated by Kaplan?CMeier Method. Male/female ratio was 0.86 (33/38). Median age was 52?years. Rates for family cancer history and goiter/thyroiditis were 22.4 and 17.8%, respectively. The most common primary site was lung (22.5%), in parallel with the literature, and 31% had the large cell neuroendocrine carcinoma histology. The second most common site was stomach. Carcinoid syndrome rate was found to be 30.6%. Half of the patients were in early stage at diagnosis. Surgical resection rate was 64.7, and 45% of the patient received chemotherapy (CT), 22% received radiotherapy. Seventy-six percent of resected patients had local disease. Thirty-two patients received CT for palliation or concurrent with radiotherapy or in adjuvant setting. Platin/etoposide combination was the most commonly used chemotherapy regimen. Chemotherapy response rate was 35.7%. Five patients had received somatostatin analogue. Radiotherapy was used in adjuvant setting in one-third of the patients. Median OS was 66?months, and median PFS was 30?months. Female gender and fifth decade seem to have higher risk. History for family cancer and goiter/thyroiditis was high in the patients with NET, though there is no data about an association between NET and thyroid disorders in the literature.     

T淋巴母细胞淋巴瘤自体干细胞移植后的长期随访观察

目的评价自体造血干细胞移植（autologous hematopoietic stem cell transplantation,AHSCT）治疗复发难治T淋巴母细胞淋巴瘤（TLBL）的临床疗效及安全性。方法本文回顾性分析AHSCT治疗后长期随访的TLBL16例,预处理方案主要为BEAM和BEAC。结果 15例患者可评价疗效,1例失访。中位随访37个月（12~132个月）,中位无进展生存时间（PFS）34.5个月。预计中位总生存时间49月。1、3、5年总生存率分别为60%、53%、32%。初治患者一线治疗有效者,接受AHSCT者预计中位总生存时间为108个月,5年总生存率、无进展生存率分别为62%、63%;复发患者挽救治疗后接受AHSCT者,中位总生存时间为22.8个月,5年总生存率、无进展生存率分别为33%、22%。初始治疗未达CR/PR的难治患者,中位生存仅21个月,5年生存率和无进展生存率分别为20%和29%。结论 AHSCT常规化疗治疗TLBL安全、有效,可提高复发难治的T淋巴母细胞淋巴瘤的远期生存,延长初治TLBL患者的无进展生存期,但复发率仍偏高,值得开展大规模临床试验进一步深入研究。     

Randomized phase II study evaluating veliparib (ABT-888) with temozolomide in patients with metastatic melanoma

BackgroundVeliparib (ABT-888) is a potent, orally bioavailable, small-molecule inhibitor of the DNA repair enzymes poly ADP-ribose polymerase-1 and -2. Veliparib enhances the efficacy of temozolomide (TMZ) and other cytotoxic agents in preclinical tumor models.Patients and methodsIn this multicenter, double-blind trial, adults with unresectable stage III or IV metastatic melanoma were randomized 1:1:1 to TMZ plus veliparib 20 or 40 mg, or placebo twice daily. Efficacy end points included progression-free survival (PFS), overall survival (OS), and objective response rate (ORR).ResultsPatients (N = 346) were randomized between February 2009 and January 2010. Median [95% confidence interval (CI)] PFS was 3.7 (3.0–5.5), 3.6 (1.9–4.1), and 2 (1.9–3.7) months in the 20-mg, 40-mg, and placebo arms, respectively. Median (95% CI) OS was 10.8 (9.0–13.1), 13.6 (11.4–15.9), and 12.9 (9.8–14.3) months, respectively; ORR was 10.3%, 8.7%, and 7.0%. Exploratory analyses showed patients with low ERCC1 expression had longer PFS when TMZ was combined with veliparib. Toxicities were as expected for TMZ. The frequencies of thrombocytopenia, neutropenia, and leukopenia were significantly increased in the veliparib groups. Grade 3 or 4 adverse events, mainly hematologic toxicities, were seen in 55%, 63%, and 41% of patients in the 20-mg, 40-mg, and placebo arms, respectively.ConclusionsMedian PFS with 20 and 40 mg veliparib almost doubled numerically compared with placebo, but the improvements did not reach statistical significance. OS was not increased with veliparib. Toxicities were similar to TMZ monotherapy, but with increased frequency.