May P-glycoprotein status be used to stratify high-grade osteosarcoma patients? Results from the Italian/Scandinavian Sarcoma Group 1 treatment protocol

The aim was to evaluate the clinical impact of P-glycoprotein in primary non-metastatic high-grade osteosarcoma patients, treated with neoadjuvant chemotherapy protocols. P-glycoprotein was assessed by immunohistochemistry on paraffin-embedded tissue samples collected at time of diagnosis from 94 osteosarcoma patients, treated with the Italian Sarcoma Group/Scandinavian Sarcoma Group 1 (ISG/SSG 1) protocol. P-glycoprotein-positivity at diagnosis was found in 53/94 ISG/SSG 1 cases (56%) and emerged as the single factor significantly associated with an unfavourable outcome from survival and multivariate analyses. A comparative analysis of the subgroup of 94 patients considered for P-glycoprotein evaluation and the whole series of ISG/SSG 1 patients showed that this marker retained its prognostic value also in the latter group. In osteosarcoma patients treated with doxorubicin-based chemotherapy protocols, P-glycoprotein overexpression at diagnosis is an important adverse prognostic factor for outcome. P-glycoprotein evaluation can therefore constitute the basis for stratifying, at diagnosis, osteosarcoma patients for whom alternative treatments may be considered.     

Prognostic impact of the epidermal growth factor receptor levels for patients with larynx and hypopharynx cancer

The aim of this study was to analyse prognostic factors for disease free interval (DFI) and overall survival (OS) among patients with larynx and hypopharynx cancer requiring a total laryngectomy. Three groups of patients were studied according to the type of treatment they received. Fifty-eight patients had total laryngectomy, 71 patients had organ preservation treatment including induction chemotherapy followed by exclusive radiotherapy, 26 patients received induction chemotherapy followed by salvage total laryngectomy. The studied potential prognostic factors were age, gender, performans status, primary tumor localization, T status, N status, tumor volume and tumoral EGFR level (fmol/mg protein). The multivariate analysis showed that both N status and tumor volume were significant for DFI and OS. EGFR level was significant only for patients treated by induction chemotherapy and exclusive radiotherapy (p = 0.05 and 0.05 for DFI and OS length, respectively). Among this group, patients with tumor EGFR levels lower and higher than 100 fmol/mg protein had 53% versus 22% and 51% versus 18% 5-year of DFI and OS rates, respectively (Log rank test: p = 0.001 and 0.0001). EGFR determination appears to be a powerful prognostic parameter for patients treated by induction chemotherapy followed by exclusive radiotherapy. Laryngectomy seems to erase the prognostic impact of EGFR expression. These results profile the use of EGFR targeting therapy for this category of patients.     

Combined Modality Therapy for Poorly Differentiated Gliomas of the Posterior Fossa in Children: A Children's Cancer Group Report

Purpose: To study the effectiveness of combined chemotherapy and radiotherapy for children with high-grade astrocytomas of the posterior fossa. Patients and Methods: In the CCG-945 study, 250 patients were treated by members of the Children's Cancer Group (CCG). Sixteen children were randomly assigned to one of two chemotherapy regimens, vincristine, lomustine, and prednisone or 8-in-1, using the same involved-field irradiation in both. Six infants received 8-in-1 chemotherapy before involved-field irradiation. All pathologic specimens had central review. Results: Twenty-two patients with an institutional diagnosis high-grade posterior fossa tumors received chemotherapy and/or irradiation. Fifteen were confirmed by central review to have high-grade gliomas. Overall survival for confirmed high-grade astrocytoma of the posterior fossa was approximately 36 ± 13% at 5 years for the children (n = 11) and 25 ± 15% at 5 years for the infants (n = 4). Conclusions: Involved-field irradiation with chemotherapy appeared to prevent extraneural and subarachnoid metastases. We also confirmed the rarity of the tumor (6% of patients registered). Further Phase III trials are necessary to improve survival in this aggressive tumor.     

Pre-treatment serum lactate dehydrogenase level is an important prognostic factor in high-grade extremity osteosarcoma

Background  Treatment of high-grade osteosarcoma remains a challenge. The prognostic significance of the pre-treatment serum lactate dehydrogenase (LDH) level is currently controversial. Patients and methods  We reviewed records from all patients diagnosed with conventional high-grade osteosarcoma at our institution over a 25-year period and analysed the prognostic significance of LDH in high-grade localised extremity osteosarcomas treated with chemotherapy. Results  Between June 1977 and March 2003, 66 patients for whom follow-up was available were diagnosed with localised high-grade extremity osteosarcoma and treated with chemotherapy. The median age was 15 years, with only 3% older than 40 years, and the median follow-up was 100 months. The median progression-free survival (PFS) was 67 months and the median overall survival (OS) was 113 months. The absence of a response to chemotherapy was correlated with a trend toward lower PFS and OS. High serum pre-treatment LDH level was associated in multivariate analyses with a poorer prognosis for both PFS (HR=8.623, 95%CI: 1.71–43.37; p=0.009) and for OS (HR=9.38; 95%CI: 1.73–50.74; p=0.009). Conclusion  In this series, the pre-treatment serum LDH level had an independent prognostic value for both PFS and OS in patients with high-grade localised extremity osteosarcoma. This measurement should be included in a large prospective prognostic series.     

Lack of correlation of functional scintigraphy with (99m)technetium-methoxyisobutylisonitrile with histological necrosis following induction chemotherapy or measures of P-glycoprotein expression in high-grade osteosarcoma.

In osteosarcoma, some studies have suggested P-glycoprotein expression is a prognostic factor. The clearance of (99m)technetium hexakis-2-methoxyisobutylisonitrile ((99m)Tc-MIBI) has been used in some tumor systems as an in vivo measure of P-glycoprotein-mediated efflux. In this study we explored the correlation between (99m)Tc-MIBI clearance and histological necrosis following induction chemotherapy and P-glycoprotein expression in osteosarcoma. The primary tumors of 20 patients with high-grade osteosarcoma were imaged at diagnosis with (99m)Tc-MIBI, and the uptake ratios and biological half-lives were calculated. P-Glycoprotein expression in the tumor tissue was determined immunohistochemically and by measuring mRNA expression of the multidrug resistance-1 gene. The histological necrosis following induction chemotherapy was assessed by the Huvos grading system. The biological half-life of (99m)Tc-MIBI ranged from 1.4 to 52.5 h. Seven of the 20 tumor samples had a favorable extent of necrosis following induction chemotherapy. The (99m)Tc-MIBI half-life and uptake ratio showed no correlation with histological necrosis following induction chemotherapy. The (99m)Tc-MIBI half-life and uptake ratio did not correlate with either measure of P-glycoprotein expression. The results of this pilot study indicate that (99m)Tc-MIBI imaging is not an effective predictor of histological necrosis following induction chemotherapy in high-grade osteosarcoma. (99m)Tc-MIBI imaging did not correlate with measures of P-glycoprotein expression in the tumor tissue.     

Neoadjuvant chemotherapy for osteosarcoma of the extremities with metastases at presentation: recent experience at the Rizzoli Institute in 57 patients treated with cisplatin, doxorubicin, and a high dose of methotrexate and ifosfamide.

BACKGROUND: Effective adjuvant or neoadjuvant regimens of chemotherapy have dramatically improved the prognosis of patients with high-grade osteosarcoma of the extremity, localized at diagnosis. Currently, little is known about patients with metastatic disease at presentation. PATIENTS AND METHODS: From May 1995 to May 2000, 57 patients with osteosarcoma of the extremity, metastatic at presentation, were treated according to the following scheme: primary chemotherapy, restaging, simultaneous resection of primary tumor and metastatic lesions, and maintenance chemotherapy. RESULTS: Thirty-five patients achieved remission. At a follow-up ranging from 2 to 7 years, seven remained continuously free of disease, one died of chemotherapy-related toxicity and 27 patients relapsed. Twenty-one of the 22 patients who never achieved remission died as a result of the tumor, as well as 20 of the 27 who achieved remission but then relapsed. Of the remaining seven relapsing patients, six are alive with uncontrolled disease, while one is alive and free of disease 24 months after the last post-relapse treatment. Two-year event-free survival (EFS) and overall survival (OS) were 21% and 55%, respectively. These results are significantly poorer than those achieved in 128 contemporary patients with non-metastatic disease at presentation, treated with the same chemotherapy protocol (2-year EFS and OS of 75% and 94%, respectively). CONCLUSIONS: The results of our study confirm that the prognosis of patients with osteosarcoma of the extremity, metastatic at presentation, remains poor, despite the use of aggressive treatments.     

Metastatic osteosarcoma at diagnosis: prognostic factors and long-term outcome--the French pediatric experience

BACKGROUND: The objective of this report was to estimate long-term outcome and prognostic factors in children and adolescents who presented with metastatic osteosarcoma at diagnosis. Patients were treated in six French pediatric oncology centers with surgery and multiagent chemotherapy, mainly with high-dose methotrexate. Their medical records were reviewed retrospectively. METHODS: The medical records of patients who were treated for metastatic osteosarcoma from 1987 to 2000 were reviewed. Patients were treated with the chemotherapy regimens recommended for nonmetastatic disease in children (the French Society of Pediatric Oncology OS 87 and OS 94 protocols) or, in a few patients, with other chemotherapy regimens. Surgical excision of the primary tumor and, when possible, of all metastatic sites was performed based on a personalized assessment of each patient's situation. RESULTS: Seventy-eight patients age < 20 years were treated. Forty-six patients (59%) had only 1 metastatic site (35 to the lungs and 11 to bone). Twenty-eight patients (36%) achieved a complete remission after combination chemotherapy and surgery. The event-free survival and overall survival rates at 5 years were 14% and 19%, respectively. To date, 14 patients (18%) have remained alive with a median follow-up of 112 months. Pretreatment features associated with a shorter event-free survival in the multivariate analysis were metastasis to at least two organs and high alkaline phosphatase level. Patients with at least 1 of these poor prognostic factors had a 2.6% event-free survival rate at 5 years despite treatment. CONCLUSIONS: The survival of patients with metastatic osteosarcoma were treated with conventional chemotherapy and surgery remained very poor. Patients should be classified into different prognostic groups and treated accordingly. New therapeutic approaches are warranted to improve the prognosis for patients with the most severe disease.     

初诊同侧锁骨上淋巴结转移乳腺癌综合治疗疗效

目的 探讨应用新辅助化疗+手术+放疗治疗初诊为锁骨上淋巴结转移乳腺癌患者疗效。方法 回顾分析1999-2013年肿瘤医院收治的65例女性乳腺癌患者的病历资料。全部患者均经初诊病理结果确诊为乳腺癌,且经病理或影像学检查证实为锁骨上淋巴结转移、无远处转移及其他第二原发癌,完整接受术前化疗+手术+术后放疗方案。采用Kaplan-Meier法计算总生存(OS)、无进展生存(PFS)及锁骨上淋巴结复发(SCFR)率,Logrank法检验差异。结果 中位随访时间66个月(6~137个月)。65例患者中5例患者治疗后锁骨上淋巴结复发。全组患者5年SCFR、OS、PFS率分别为9%、72%、50%。术前化疗后锁骨上淋巴结完全缓解是影响OS因素,是否完全缓解患者5年OS率分别为81%和54%(P=0.035)。初诊锁骨上淋巴结大小 (短径≤1 cm、>1 cm)为5年SCFR(分别为0%、21%,P=0.037)和5年OS(分别为86%、56%,P=0.001)的高危因素。结论 对于初诊为锁骨上淋巴结转移的乳腺癌患者,完整接受术前化疗+手术+术后放疗方案治疗后的OS率较高,锁骨上区放疗可获得良好的肿瘤局部控制。     

Limb-saving surgery, survival, and prognostic factors for osteosarcoma: the Hungarian experience

BACKGROUND AND OBJECTIVES: There are many factors thought to have an influence on the prognosis of osteosarcoma that have been reported in the literature. Their significance, however, still remains controversial in most cases. Experience with osteogenic sarcoma (OS) was reviewed in order to evaluate surgical results and survival and to determine the prognostic factors. METHODS: Ninety-six patients with high-grade osteosarcoma of the extremities were treated between 1986 and 1997 in the authors' institution. They were divided into 3 groups: In group I, all 75 patients with nonmetastatic OS received intensive chemotherapy (high-dose methotrexate, doxorubicin, ifosfamide, and cisplatin) and underwent surgery. In group II, 9 patients already had metastases at the time of referral. In group III, 12 patients received chemotherapy in delayed or suboptimal form. Results and Conclusions In group I, there were local recurrences in 3 patients (7%) and metastases in 8 patients (20%) with limb-saving, whereas these numbers were 1 (3%) and 14 (38%) in those who had amputation. The 5-year disease-free survival (DFS) was 72% and 69% in the limb-saving and amputation groups, respectively. In groups II and III, 5-year DFS was extremely poor, 10% and 20% only, underlining the importance of stage and intensity of chemotherapy, respectively. With univariate analysis, sex, duration of symptoms, and radiographic appearance of OS had no prognostic value, whereas tumor volume <60 cm(3), wide or radical surgical margin, distal location of OS, cartilagineous ground substance <20%, and response to chemotherapy were positive prognostic factors. The last 4 variables maintained their significance in the multivariate Cox model as well. Age >30 years showed indirect negative influence on the final outcome through enhanced intolerability to the drugs and less cooperability of the patients. The results on survival with limb-saving surgery were well comparable with those of amputation.     

Metachronous skeletal osteosarcoma in patients treated with adjuvant and neoadjuvant chemotherapy for nonmetastatic osteosarcoma.

PURPOSE: The prognosis for patients who develop metachronous skeletal osteosarcoma (OS) has been considered grave compared with that for patients with relapse limited to the lungs. We investigated the incidence and outcome of metachronous skeletal OS after initial treatment of the primary tumor. PATIENTS AND METHODS: Twenty-three (median age 18.7 years) of 426 patients with nonmetastatic, high-grade primary OS treated at Memorial Sloan-Kettering Cancer Center (New York, NY) between February 1973 and May 2000 developed metachronous skeletal OS. Initial therapy included combination chemotherapy and surgery. Treatment of subsequent relapses consisted of chemotherapy or radiation alone or surgery with or without additional individualized chemotherapy. RESULTS: The median time from the diagnosis of primary OS to the development of metachronous OS was 1.4 years (range, 0.2 to 11.3 years). Median survival was 1.5 years (95% confidence interval [CI], 0.8 to 6.9 years). Two- and 5-year postmetachronous overall survival was 43.5% (95% CI, 23.2% to 63.7%) and 33% (95% CI, 13% to 53%), respectively. At last follow-up (range, 0.1 to 12.8 years), five (30.4%) patients were alive with no evidence of disease (range, 1.7 to 12.8 years; median, 4.4 years). For 11 patients who developed metachronous OS 24 months or more from initial diagnosis, 5-year postmetachronous survival rate for patients receiving combined modality versus monotherapy was 83% (95% CI, 54% to 100%) and 40% (95% CI, 0% to 83%), respectively. CONCLUSION: In a small subset of patients who developed late metachronous OS, combined-modality therapy with surgery and aggressive chemotherapy may result in long-term postmetachronous survival. This implies that principles used in treatment of primary OS may be applied to patients with late metachronous skeletal OS.     

Treatment of embryonal tumors with multilayered rosettes with carboplatin/etoposide induction and high-dose chemotherapy within the prospective P-HIT trial

BackgroundEmbryonal tumors with multilayered rosettes (ETMR) are highly aggressive tumors occurring in early childhood. Published clinical data refer to retrospective, heterogeneously treated cohorts. Here, we describe the outcome of patients treated according to the prospective P-HIT trial and subsequent HIT2000-interim-registry.Patients and methodsAge-stratified treatment included carboplatin/etoposide induction, tandem high-dose chemotherapy (“CARBO/ETO + HDCT”), and response-stratified radiotherapy. Patients with centrally reviewed neuropathological and molecularly confirmed diagnosis of ETMR recruited within the P-HIT trial (2001-2011; n = 19), the HIT2000-interim-registry (2012-2014; n = 12), and earlier HIT trials (n = 4) were selected for analysis.ResultsAge-adjusted incidence rate was 1.35 per 1 million children (aged 1-4 years) in the years 2012-2014. Median age at diagnosis for 35 patients was 2.9 years. Metastases at diagnosis were detected in 9 patients. One patient died due to postoperative complications. For 30 patients with non-brainstem tumor location, 5-year progression-free survival (PFS) and overall survival (OS) were 35% and 47% after treatment with CARBO/ETO + HDCT (n = 17), compared to 0% and 8% with other treatments (n = 13, P[OS] = .011). All 4 patients with brainstem tumor died within 10 months after diagnosis. By multivariable analysis, supratentorial location: (HR [PFS]: 0.07 [95%CI: 0.01-0.38], P = .003), localized disease (M0): (HR [OS] M0, no residual tumor: 0.30 [95%CI: 0.009-1.09], P = .068; M0, residual tumor: 0.18 [95%CI: 0.04-0.76], P = .020), and CARBO/ETO + HDCT treatment (HR [OS]: 0.16 [95%CI: 0.05-054], P = .003) were identified as independent prognostic factors. Of 9 survivors, 6 were treated with radiotherapy (craniospinal 4; local 2).ConclusionsOur data indicate improved survival with intensified chemotherapy (CARBO/ETO + HDCT). However, despite intensive treatment, the outcome was poor. Thus, innovative therapies need to be evaluated urgently in an upfront setting.     

A high tumor-associated macrophage content predicts favorable outcome in follicular lymphoma patients treated with rituximab and cyclophosphamide-doxorubicin-vincristine-prednisone.

PURPOSE: Tumor-associated macrophage (TAM) content predicts survival in follicular lymphoma (FL) patients treated with chemotherapy. The aim of this study was to determine how combination of rituximab with chemotherapy influences TAM-associated clinical outcome. EXPERIMENTAL DESIGN: Expression of a macrophage marker, CD68, was determined immunohistochemically from FL samples of 96 patients treated with rituximab and cyclophosphamide-Adriamycin-vincristine-prednisone regimen. Of them, 71 received therapy at diagnosis and 25 at relapse. Neutrophil and CD3+ lymphocyte counts were also measured. The median follow-up time for the cohort was 54 months. Fourty-five patients previously treated with chemotherapy served as a control group. RESULTS: Consistent with previous studies, high TAM amount was associated with adverse outcome in chemotherapy-treated patients (P = 0.026). In contrast, after rituximab and cyclophosphamide-doxorubicin-vincristine-prednisone regimen, high TAM content correlated with longer survival rates. According to Kaplan Meier estimates, the median progression free survival (PFS) was not reached for patients with high TAM content compared with 45 months for patients with low TAM scores (P = 0.006). A trend toward a better overall survival (OS) at 5 years was also observed for patients with high TAM content (OS, 97% versus 90%, P = 0.116). The positive prognostic value of TAMs was seen both for the patients treated at diagnosis and at relapse. In multivariate analyses, TAM content remained an independent prognostic factor for OS and PFS. Neutrophil and CD3+ lymphocyte counts did not correlate with outcome. CONCLUSIONS: The data suggest that high TAM score is associated with a favorable prognosis in FL patients treated with immunochemotherapy.     

Investigation of MRP-1 protein and MDR-1 P-glycoprotein expression in invasive breast cancer: a prognostic study

The efficacy of breast cancer treatment is limited by the development of resistance to various chemotherapeutic agents. We conducted a retrospective study of the expression of 2 drug resistance efflux pumps, MRP-1 and MDR-1 Pgp, in 177 invasive breast carcinomas. Immunohistochemical expression of these proteins was correlated with clinicopathologic characteristics as well as relapse-free survival (RFS) and overall survival (OS) times. MDR-1 Pgp was associated strongly with higher histologic grade (grade III). A highly significant association was shown between MDR-1 Pgp and MRP-1 expression (p < 0.01), 47.4% of patients expressing both proteins; MRP-1 was expressed in approximately 61% of patients and MDR-1, in approximately 66% of patients. No association was shown in the overall group between either MDR-1 Pgp or MRP-1 and any of the other clinicopathologic features. Kaplan-Meier analysis revealed that in a subset of patients with either high-grade (grade III) stage 1 (node-negative) or stage 2 (node-positive) tumours who were treated with surgery followed by adjuvant chemotherapy, MRP-1 expression in <25% of tumour cells at diagnosis was significantly associated with improved RFS (p < 0.02) and OS (p < 0.02). Using multivariate analysis, MRP-1 expression in <25% of tumour cells at diagnosis was identified as an independent, significant prognostic factor for RFS (p < 0.01) and OS (p < 0.01) in this patient group but not in other groups. In this subgroup, no significant correlation was observed between expression of MDR-1 Pgp and MRP-1. While the number of patients with high-grade tumours treated with adjuvant chemotherapy was small and further confirmatory research is warranted, it appears that assessment of MRP-1 expression at diagnosis may offer useful prognostic information in subgroups of patients with stage 1 or stage 2 high-grade tumours who receive CMF-based adjuvant chemotherapy. Given the known substrate specificities of MRP-1, any mechanistic relationship between MRP-1 expression and CMF resistance remains unclear. No association was shown between MDR-1 Pgp expression and either RFS or OS time in any subgroup of patients.     

Primary metastatic osteosarcoma: presentation and outcome of patients treated on neoadjuvant Cooperative Osteosarcoma Study Group protocols.

PURPOSE: To determine demographic data and define prognostic factors for long-term outcome in patients presenting with high-grade osteosarcoma of bone with clinically detectable metastases at initial presentation. PATIENTS AND METHODS: Of 1,765 patients with newly diagnosed, previously untreated high-grade osteosarcomas of bone registered in the neoadjuvant Cooperative Osteosarcoma Study Group studies before 1999, 202 patients (11.4%) had proven metastases at diagnosis and therefore were enrolled onto an analysis of demographic-, tumor-, and treatment-related variables, response, and survival. The intended therapeutic strategy included pre- and postoperative multiagent chemotherapy as well as aggressive surgery of all resectable lesions. RESULTS: With a median follow-up of 1.9 years (5.5 years for survivors), 60 patients were alive, 37 of whom were in continuously complete surgical remission. Actuarial overall survival rates at 5 and 10 (same value for 15) years were 29% (SE = 3%) and 24% (SE = 4%), respectively. In univariate analysis, survival was significantly correlated with patient age, site of the primary tumor, number and location of metastases, number of involved organ systems, histologic response of the primary tumor to preoperative chemotherapy, and completeness and time point of surgical resection of all tumor sites. However, after multivariate Cox regression analysis, only multiple metastases at diagnosis (relative hazard rate [RHR] = 2.3) and macroscopically incomplete surgical resection (RHR = 2.4) remained significantly associated with inferior outcomes. CONCLUSION: The number of metastases at diagnosis and the completeness of surgical resection of all clinically detected tumor sites are of independent prognostic value in patients with proven primary metastatic osteosarcoma.     

Oral cyclophosphamide therapy for patients with residual or relapsed indolent-type lymphoma after initial treatment for aggressive lymphomas. A sub-group of patients with apparent transformed indolent lymphoma

Lymph node or bone marrow biopsy from sixty-one patients affected by aggressive non-Hodgkin lymphomas (NHL) were retrospectively evaluated to assess the histology at relapse. Eighteen cases (29.5%) were proven to have relapsed or persistent low-grade lymphoma after conventional therapy. In 5/18 patients association of low and high-grade lymphoma was detectable at diagnosis by bone marrow biopsy. In the remaining 13/18 no evidence of follicular lymphoma was detected at diagnosis. The outcome of these patients was compared to that of 43 patients relapsed without change in histology and treated by a second line therapy. Of these 43 patients, 13 were not responders (NR), 10 achieved a partial remission (PR) and 18 complete remission (CR). Two were lost during follow-up. The 18 patients with residual/relapsed indolent subtype received oral cyclophosphamide (100 mg/day for 15 days every month for six months): 3 of them had NR, 5 CR, and 10 PR. The overall survival (OS) median time was 39 months in low-grade resistant/relapsed patients and 20 months in patients with aggressive histology. OS at 24 months was 71 and 41%, respectively, (p < 0.02). Most of the patients with high-grade disease were refractory or relapsed after a median of five months, whereas cases with low-grade NHL showed a long lasting stable PR. We suggest that the higher grade patients with residual or relapsed low grade lymphoma were, in fact, transformed low-grade at diagnosis and, after removing the more aggressive component by chemotherapy, it is possible to manage these patients by conventional therapy for indolent lymphomas.     

Treatment results and prognostic factors in primary thyroid lymphoma patients: a Rare Cancer Network study

Background: This study analyzed prognostic factors and treatment outcomes of primary thyroid lymphoma.Patients and Methods: Data were retrospectively collected for 87 patients (53 stage I and 34 stage II) with median age 65 years. Fifty-two patients were treated with single modality (31 with chemotherapy alone and 21 with radiotherapy alone) and 35 with combined modality treatment. Median follow-up was 51 months.Results: Sixty patients had aggressive lymphoma and 27 had indolent lymphoma. The 5- and 10-year overall survival (OS) rates were 74% and 71%, respectively, and the disease-free survival (DFS) rates were 68% and 64%. Univariate analysis revealed that age, tumor size, stage, lymph node involvement, B symptoms, and treatment modality were prognostic factors for OS, DFS, and local control (LC). Patients with thyroiditis had significantly better LC rates. In multivariate analysis, OS was influenced by age, B symptoms, lymph node involvement, and tumor size, whereas DFS and LC were influenced by B symptoms and tumor size. Compared with single modality treatment, patients treated with combined modality had better 5-year OS, DFS, and LC.Conclusions: Combined modality leads to an excellent prognosis for patients with aggressive lymphoma but does not improve OS and LC in patients with indolent lymphoma.     

Baseline Radiomic Signature to Estimate Overall Survival in Patients With NSCLC

IntroductionWe aimed to define a baseline radiomic signature associated with overall survival (OS) using baseline computed tomography (CT) images obtained from patients with NSCLC treated with nivolumab or chemotherapy.MethodsThe radiomic signature was developed in patients with NSCLC treated with nivolumab in CheckMate-017, -026, and -063. Nivolumab-treated patients were pooled and randomized to training, calibration, or validation sets using a 2:1:1 ratio. From baseline CT images, volume of tumor lesions was semiautomatically segmented, and 38 radiomic variables depicting tumor phenotype were extracted. Association between the radiomic signature and OS was assessed in the nivolumab-treated (validation set) and chemotherapy-treated (test set) patients in these studies.ResultsA baseline radiomic signature was identified using CT images obtained from 758 patients. The radiomic signature used a combination of imaging variables (spatial correlation, tumor volume in the liver, and tumor volume in the mediastinal lymph nodes) to output a continuous value, ranging from 0 to 1 (from most to least favorable estimated OS). Given a threshold of 0.55, the sensitivity and specificity of the radiomic signature for predicting 3-month OS were 86% and 77.8%, respectively. The signature was identified in the training set of patients treated with nivolumab and was significantly associated (p < 0.0001) with OS in patients treated with nivolumab or chemotherapy.ConclusionsThe radiomic signature provides an early readout of the anticipated OS in patients with NSCLC treated with nivolumab or chemotherapy. This could provide important prognostic information and may support risk stratification in clinical trials.     

国际预后分数预测晚期霍奇金淋巴瘤预后的可行性研究

背景与目的:目前,按标准方案治疗晚期霍奇金淋巴瘤(HodgkinNslymphoma,HL)治愈率可达60%。晚期HL国际预后因素课题组研究总结出晚期初治HL的7个不良预后因素:男性、年龄≥45岁、Ⅳ期、白细胞增高、淋巴细胞减少、低血红蛋白、低白蛋白,并据此提出了国际预后分数(internationalprognosticscore,IPS)的概念。本研究旨在探索应用IPS预测晚期HL预后的价值。方法:回顾性分析1980年1月至2004年12月中山大学肿瘤防治中心初次治疗的141例晚期HL,按照确诊时患者不良预后因素的数目计算IPS。采用Kaplan-Meier法进行生存分析,生存率的比较用log-rank检验,采用Cox部分风险模型进行多因素分析,按IPS分组计算生存率并进行生存率比较。结果:141例晚期HL患者5年无失败生存率(failurefreesurvival,FFS)为57.6%,5年总生存率(overallsurvival,OS)为68.1%。IPS=0～1、2、3和IPS≥4组的5年FFS分别为67.7%、63.2%、61.8%、34.9%;5年OS分别为81.0%、75.5%、70.3%、42.3%。低危患者(IPS0～2)和高危患者(IPS≥3)5年FFS分别为65.4%和48.9%(P=0.012);5年OS分别为78.4%和57.1%(P=0.004)。接受ABVD方案[阿霉素(A)、博来霉素(B)、长春花碱(V)、氮烯咪胺(D)]或MOPP方案[氮芥(M)、长春新碱(O)、甲基苄肼(P)、强的松(P)]治疗的低危患者的5年OS均优于高危患者;接受ABVD治疗的高危晚期HL患者5年FFS和OS均显著优于接受MOPP方案治疗者。多因素分析显示B症状、结外病变、接受MOPP方案化疗为晚期HLFFS和OS独立预后不良因素。结论:IPS对晚期HL的预后有较好的预测价值;高危晚期HL患者接受MOPP方案化疗生存比接受ABVD方案差,推荐接受ABVD方案或更强的方案化疗。     

Prognostic factors and long-term survivorship in patients with recurrent or metastatic carcinoma of the head and neck

BACKGROUND: The current study was conducted to identify prognostic factors and report the characteristics of long-term survivors in patients with recurrent or metastatic carcinoma of the head and neck who were treated with cisplatin-based combination chemotherapy in two randomized, Phase III trials conducted by the Eastern Oncology Cooperative Group (ECOG) (E1393 and E1395). METHODS: The authors analyzed prognostic factors for response and survival by combining data from the E1393 trial, which compared cisplatin plus paclitaxel at two dose levels, with data from the E1395 trial, which compared cisplatin plus paclitaxel with cisplatin plus 5-fluorouracil (5-FU), using logistic regression and Cox regression models. RESULTS: A total of 399 eligible patients were included. The median follow-up was 4.7 years. The 1-year overall survival (OS) rate for all patients was 32%, the median OS was 7.8 months, and the objective response rate was 32%. On multivariate analysis, the following were found to be independent unfavorable predictors of objective response: weight loss of > 5%, an ECOG performance status of 1 (vs. 0), residual disease at the primary tumor site, a primary tumor site other than the oropharynx, prior radiation therapy (RT) (P = 0.056), and well/moderate tumor cell differentiation (P = 0.067). Independent unfavorable prognostic factors for OS were weight loss, an ECOG performance status of 1 (vs. 0), well/moderate tumor cell differentiation, a primary tumor in the oral cavity or hypopharynx, and prior RT. The following were found to be independent unfavorable prognostic factors for time to disease progression: well/moderate tumor cell differentiation, a oral cavity or hypopharyngeal primary tumor, and prior RT. Patients with < or = 2 adverse prognostic factors were reported to have a median OS of 1 year, whereas patients with 3-5 adverse prognostic factors were found to have a median OS of 0.5 years (P < 0.0001). Forty-nine patients (12%) survived for > or = 2 years and 6 patients were alive at 5 years. Two-year survivors were more likely to have achieved an objective response to chemotherapy, have poor tumor cell differentiation, be white, have an ECOG performance status of 0, and have received no prior RT. CONCLUSIONS: Clinical parameters and tumor cell differentiation appear to be strong pretreatment predictors of outcome in patients with carcinoma of the head and neck and should be considered in the design of future randomized trials. A small percentage of patients with recurrent head and neck carcinoma can achieve long-term survival.     

Tumor volume and uterine body invasion assessed by MRI for prediction of outcome in cervical carcinoma treated with concurrent chemotherapy and radiotherapy

OBJECTIVE: The aim of this study was to evaluate the prognostic significance of primary tumor volume and uterine body invasion assessed by pre-treatment MRI for uterine cervical cancer patient treated with concurrent chemotherapy and radiotherapy. METHODS: A retrospective analysis of 106 patients with IB-IIIB cervical carcinoma was performed. Potential prognostic factors were stage, clinical tumor diameter, histology, age, pelvic lymph node, vaginal extension, parametrial invasion, tumor volume and uterine body invasion status. Multivariate analyses were performed to identify the prognostic factor for overall survival (OS) and disease-free survival (DFS). RESULTS: The 5-year OS, DFS rate were 59.7 and 56.6%. Using multivariate analyses, a large tumor volume (>/=30 ml; P = 0.012) and uterine body invasion (P = 0.020) and positive pelvic lymph node (LN) enlargement (P = 0.040) showed a significantly unfavorable influence on OS. Using these three factors, patients were divided into four subgroups: the OS rates of patients with risk 0 (volume <30 ml, no uterine body invasion, and negative LN), risk 1 (one of these three factors), risk 2 (two of these three factors) and risk 3 (volume >/=30 ml, uterine body invasion, and positive LN) were 96.3, 77.5, 53.0 and 14.8%, respectively (P < 0.0001). CONCLUSIONS: Tumor volume and uterine body invasion determined by MRI were significant prognostic factors for patients with cervical carcinoma. Pelvic lymph node enlargement diagnosed by CT also proved to be a significant prognostic factor in OS. Using these three parameters, we devised a practical and effective model to predict OS.