Factors For Better Overall Survival Research Articles

Prognostic value of circulating vitamin D binding protein, total, free and bioavailable 25-hydroxy vitamin D in patients with colorectal cancer.

Numerous studies have suggested that there was a significantly positive association between circulating total 25-hydroxyvitamin D (25(OH)D) and survival in colorectal cancer patients. Moreover, plasma vitamin D was also found significantly associated with the concentration of vitamin D binding protein (VDBP). However, there was no paper to clarify the prognostic value of VDBP, free and bioavailable 25(OH)D in colorectal carcinogenesis. The aim of this study was to comprehensively assess the prognostic value of VDBP, total, free and bioavailable 25(OH)D in stage I-III colorectal cancer patients. A total of 206 colorectal cancer patients were enrolled in this prospective study. Preoperative plasma total 25(OH)D and VDBP concentrations were measured by direct enzyme-linked immunosorbent assay, and albumin concentration was measured by Beckman automatic biochemical analyzer. Free and bioavailable 25(OH)D concentrations were calculated based on the concentrations of plasma VDBP, total 25(OH) D and albumin. X-title program was used to determine the optimal cut-off values of VDBP, total, free and bioavailable 25(OH)D. Results showed that elevated free and bioavailable 25(OH)D were significantly associated with better 5-year overall survival (OS) by univariate analysis. By multivariate cox analysis, we also found that the high level of free 25(OH)D (HR = 0.442, 95%CI = 0.238–0.819, P < 0.010) could be identified as an independent factor for better OS. In conclusion, our study suggested that higher levels of free and bioavailable 25(OH)D were associated with better OS in stage I-III colorectal cancer patients. Moreover, free 25(OH)D could be considered as an independent prognostic biomarker for OS.

Might radiation therapy in addition to chemotherapy improve overall survival of patients with non-oligometastatic Stage IV non-small cell lung cancer?: Secondary analysis of two prospective studies.

BackgroundThe role of radiation therapy in addition to chemotherapy has not been well established in non-oligometastatic Stage IV non-small cell lung cancer (NSCLC). We aimed to investigate overall survival (OS) of non-oligometastatic Stage IV NSCLC treated with chemotherapy with concurrent radiation to the primary tumor.MethodsEligible patients were screened from two prospective studies. Oligometastatic and non-oligometastatic NSCLC were defined as having < 5 and ≥5 metastatic lesions, respectively. Prognostic factors for OS were identified by using univariate and multivariate analysis. Landmark analysis and propensity-score matching (PSM) were each performed to further adjust for confounding.ResultsA total of 274 patients were identified as the study cohort: 183 had non-oligometastatic disease. For all 274 patients, those who received a radiation dose ≥63 Gy to the primary tumor and had oligometastatic disease had better OS (P < 0.001 and P = 0.017, respectively). When patients were subdivided into those with oligometastatic or non-oligometastatic disease, a radiation dose ≥ 63 Gy remained a significant prognostic factor for better OS. For non-oligometastatic patients, multivariate analysis showed that receiving ≥63 Gy radiation, having a GTV <146 cm3, having response to chemotherapy, and having stable or increased post-treatment KPS independently predicted better OS (P = 0.018, P = 0.014, P = 0.014, and P = 0.001). After PSM in non-oligometastatic patients, a higher radiation dose (≥63 Gy) remained to be correlated with better OS. By landmark analysis, aggressive radiation (≥63 Gy) remained to be correlated with better OS in Pre-PSM cohort (P = 0.005) and Post-PSM cohort (P = 0.004).ConclusionsRadiation dose, primary tumor volume, response to chemotherapy and KPS after treatment are associated with OS in patients with non-oligometastatic disease; on basis of effective system chemotherapy, aggressive thoracic radiotherapy may prolong OS.

Abstract A145: The prognostic significance of programmed cell death-ligand 1 expression in pulmonary squamous cell carcinoma

Abstract Introduction: The programmed cell death-ligand 1 (PD-L1) pathway plays an important role in maintaining immune homeostasis. PD-L1 pathway may also protect tumor from attack of cytotoxic T cells. The prognostic significance of PD-L1 expression in pulmonary squamous cell carcinoma has not been well demonstrated. Methods: A total of 98 patients with resected pulmonary squamous cell carcinoma were included in the study. PD-L1 expression was determined by immunohistochemistry in tumor specimens. Relationship between PD-L1 expression and clinicopathological variables was investigated. The prognostic value of PD-L1 expression in overall survival (OS) and probability of freedom from recurrence [FFR] was also demonstrated in the study. Results: PD-L1 expression was identified in 72 (73.5%) of the 98 lung tumor samples. PD-L1 expression was significantly associated with advanced stage (P = 0.045). PD-L1 expression (hazard ratio, 0.347; 95% confidence interval, 0.148 to 0.814; P = 0.015) was a significant prognostic factor for better OS in multivariate analysis. For patients with stage I/II lung squamous cell carcinoma, PD-L1 expression was a significant prognostic factor for better OS (HR, 0.299; 95% CI, 0.114 to 0.786; P = 0.014) and probability of FFR (HR, 0.346; 95% CI, 0.143 to 0.836; P = 0.025) in multivariate analysis. Conclusions: PD-L1 expression was significantly associated with advanced stage in pulmonary squamous cell carcinoma. PD-L1 expression was a significant prognostic factor for better OS in patients with pulmonary squamous cell carcinoma, and also a significant prognostic factor for better probability of FFR in those with early-stage pulmonary squamous cell carcinoma. Citation Format: Jung-Jyh Hung, Yu-Chung Wu, Wen-Hu Hsu. The prognostic significance of programmed cell death-ligand 1 expression in pulmonary squamous cell carcinoma [abstract]. In: Proceedings of the Second CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; 2016 Sept 25-28; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(11 Suppl):Abstract nr A145.

Outcome and Predictive Factors in Uterine Carcinosarcoma Using Postoperative Radiotherapy: A Rare Cancer Network Study.

Uterine carcinosarcomas (UCS) are rare tumors. Consensus regarding therapeutic management in non-metastatic disease is lacking. This study reports on outcome and predictive factors when using postoperative radiotherapy. We analyzed a retrospective analysis in 124 women treated between 1987-2007 in the framework of the Rare-Cancer-Network. Median follow-up was 27 months. Postoperative pelvic EBRT was administered in 105 women (85%) and 92 patients (74%) received exclusive or additional vaginal brachytherapy. Five-year overall survival (OS), disease-free survival (DFS), cancer specific survival (CSS) and locoregional control (LRC) were 51.6% (95% CI 35-73%), 53.7% (39-71%), 58.6% (38-74%) and 48% (38-67%). Multivariate analysis showed that external beam radiation therapy (EBRT) >50Gy was an independent prognostic factor for better OS (P=0.03), CSS (P=0.02) and LRC (P=0.01). Relative risks (RR) for better OS (P=0.02), DFS (P=0.04) and LRC (P=0.01) were significantly associated with younger age (≤60 years). Higher brachytherapy (BT)-dose (>9Gy) improved DFS (P=0.04) and LRC (P=0.008). We concluded that UCS has high systemic failure rate. Local relapse was reduced by a relative risk factor of over three in all stages of diseases when using higher doses for EBRT and brachytherapy. Postoperative RT was most effective in UCS stage I/II-diseases.

Oral Maintenance Chemotherapy with 6-Mercaptopurine and Methotrexate in Patients with Acute Myeloid Leukemia Ineligible for Transplantation.

For decades, maintenance chemotherapy has failed to improve the cure rate or prolong the survival of patients with acute myeloid leukemia (AML), other than those with acute promyelocytic leukemia. Immediately after the first complete remission following consolidation therapy was obtained, oral maintenance chemotherapy (daily 6-mercaptopurine and weekly methotrexate) was given and continued for two years in transplant-ineligible AML patients. Leukemia-free survival (LFS) and overall survival (OS) were studied and compared between these patients and the historical control group who did not receive maintenance therapy. Consecutive 52 transplant-ineligible AML patients were analyzed. Among these patients, 27 received oral maintenance chemotherapy. No significant difference was found in the patients' characteristics between the maintenance and the control groups. The median OS was 43 (95% CI, 19-67) and 19 (95% CI, 8-30) months in the maintenance and the control groups, respectively (P = 0.202). In the multivariate analysis, the presence of maintenance therapy was an independent prognostic factor for better OS (P = 0.021) and LFS (P = 0.024). Clinical benefit from maintenance chemotherapy was remarkable in older patients (≥ 60 yr) (P = 0.035), those with intermediate or unfavorable cytogenetics (P = 0.006), those with initial low blast count in peripheral blood (P = 0.044), and those receiving less than two cycles of consolidation therapy (P = 0.017). Maintenance oral chemotherapy as a post-remission therapy can prolong the survival of patients with AML who are not eligible for transplantation, particularly older patients, those with intermediate or unfavorable cytogenetics, those with initial low blast count, and those receiving less than two cycles of consolidation therapy.

Results and prognostic factors of 3-dimensional conformal radiotherapy and intensity-modulated radiotherapy for esophageal carcinoma.

The aim of this study was to summarize the outcomes and prognostic factors of 3-dimensional conformal radiotherapy (3D-CRT) and intensity-modulated radiotherapy (IMRT) for esophageal carcinoma in our institute. Five hundred ninety-two patients received radiotherapy for esophageal carcinoma (123 with 3D-CRT, 469 with IMRT) from January 2002 to March 2012. Three hundred sixty patients received radiotherapy alone and 232 patients received radiotherapy and chemotherapy. The endpoints were overall survival (OS), progression-free survival (PFS). Kaplan-Meier analysis was used to calculate endpoints, the log-rank test for univariate analysis, and multivariate analysis to identify independent prognostic factors. The median follow-up time was 22.6 months and the median dose was 60 Gy. The 1-year OS, PFS were 65.3%, 52.1%; the 3-year OS, PFS were 34.0%, 28.0%; and the 5-year OS, PFS were 23.5%, 19.6%. The median OS was 20 months (95% CI: 17.9-22.1 months) and the median PFS was 14 months (95% CI: 11.8-16.2 months). Univariate analysis indicated that sex, N-stage, M-stage, TNM stage, radiotherapy dose, weight loss before treatment, smoking, and drinking affected OS and PFS (p < 0.05 for all). T-stage affected OS (p = 0.042), but no significant influence on PFS (p = 0.101). The independent prognostic factors for better OS and PFS were early clinical TNM stage, high radiotherapy dose, and female sex (p < 0.05 for all). The results of esophageal carcinoma patients treated with 3D-CRT and IMRT with or without chemotherapy were promising. Clinical TNM stage, radiotherapy dose and sex were the independent prognostic factors for OS and PFS.

The survival outcomes and prognosis of stage IV non-small-cell lung cancer treated with thoracic three-dimensional radiotherapy combined with chemotherapy.

BackgroundThe impact of thoracic three-dimensional radiotherapy on the prognosis for stage IV non-small-cell lung cancer is unclear. This study is to investigate survival outcomes and prognosis in patients with stage IV non-small cell lung cancer (NSCLC) treated with thoracic three-dimensional radiotherapy and systemic chemotherapy.MethodsNinety three patients with stage IV NSCLC had received at least four cycles of chemotherapy and thoracic three-dimensional radiotherapy of ≥40 Gy on primary tumors. The data from these patients were retrospectively analyzed.ResultsOf the 93 patients, the median survival time (MST) was 14.0 months, and the 1, 2, and 3-year survival rates were 54.8%, 20.4%, and 12.9%, respectively. The MST of patients received radiation dose to primary tumor ≥63Gy and <63 Gy for primary tumor were 15.0 and 8.0 months, respectively (P = 0.001). Patients had metastasis to a single site and lower tumor volume (<170 cm3) also produced longer overall survival time (P = 0.002, P = 0.020, respectively). For patients with metastasis at a single site, thoracic radiation dose ≥63 Gy remained a prognostic factor for better overall survival (P = 0.030); patients with metastases at multiple sites, radiation dose ≥63 Gy had a trend to improve overall survival (P = 0.062). A multivariate analysis showed that radiation dose ≥63 Gy (P = 0.017) and metastasis to a single site (P = 0.038) are associated with better overall survival, and the volume of primary tumor was marginally correlated with OS (P = 0.054).ConclusionsIn combination with systemic chemotherapy, radiation dose ≥63 Gy on primary tumor and metastasis to a single site are significant factors for better OS, aggressive thoracic radiotherapy may have an important role in improving OS.

Long-term outcomes of combined androgen blockade therapy in stage IV prostate cancer.

To clarify which subset of stage IV prostate cancer patients benefit from combined androgen blockade (CAB) using Japanese nationwide database. A total of 3,752 patients with stage IV disease from the prospective nationwide cohort database of the Japan Study Group of Prostate Cancer (J-CaP) were enrolled. All patients started primary androgen deprivation therapy (PADT) between 2001 and 2003, and the present study was performed using the data set from December 2011. Patients were divided into two groups according to initial treatments: CAB with luteinizing hormone-releasing hormone agonist (LHRH) plus anti-androgen (AA) and non-CAB treatments such as LHRH monotherapy. The overall survival (OS) and cancer-specific survival (CSS) for each group were estimated by the Kaplan-Meier method. A total of 2,967 patients (79.1%) received CAB. Overall, no significant difference was observed in OS and CSS between the CAB group and the non-CAB group. However, CAB resulted in significantly better OS and CSS compared to non-CAB in patients with very high Japan Cancer of the Prostate Risk Assessment (J-CAPRA) scores of ten or greater (P = 0.007 and 0.013, respectively). Multivariate analysis revealed that CAB was an independent predictive factor for better OS (P = 0.013, hazard ratio = 0.83). Based on large-scale nationwide database, as PADT for prostate cancer patients with very high-risk disease, CAB resulted in better OS than other endocrine treatments.

The Use of Novel Drugs Can Effectively Improve Response, Delay Relapse and Enhance Overall Survival in Multiple Myeloma Patients with Renal Impairment

BackgroundRenal impairment is a common feature in multiple myeloma and is considered a poor prognostic factor.AimTo determine the impact of novel drugs (i.e. bortezomib, lenalidomide and thalidomide) in the treatment of myeloma patients with renal impairment. The primary endpoint was overall survival and secondary endpoints were time to next treatment and response.MethodsThe study population included all patients diagnosed with treatment-demanding multiple myeloma January 2000 to June 2011 at 15 Swedish hospitals. Renal impairment was defined as an estimated glomerular filtration rate under 60 mL/min/1.73 m2.ResultThe study population consisted of 1538 patients, of which 680 had renal impairment at diagnosis. The median overall survival in patients with renal impairment was 33 months, which was significantly shorter than 52 months in patients with normal renal function (P<0.001). Novel agents in first line improved overall survival (median 60 months) in non-high-dose treated patients with renal impairment (n = 143) as compared to those treated with conventional cytotoxic drugs (n = 411) (median 27 months) (P<0.001). In the multivariate analysis up front treatment with bortezomib was an independent factor for better overall survival in non-high-dose treated renally impaired patients. High-dose treated renally impaired patients had significantly better median overall survival than non-high-dose ones (74 versus 26 months) and novel drugs did not significantly improve survival further in these patients. Patients with renal impairment had both a shorter median time to next treatment and a lower response rate than those with normal renal function. However, novel drugs and high dose treatment lead to a significantly longer time to next treatment and the use of novel agents significantly improved the response rate of these patients.ConclusionHigh dose treatment and novel drugs, especially bortezomib, can effectively overcome the negative impact of renal impairment in patients with multiple myeloma.

Radiation dose and survival of patients with stage IV non-small cell lung cancer undergoing concurrent chemotherapy and thoracic three-dimensional radiotherapy: reanalysis of the findings of a single-center prospective study.

BackgroundThe objective of this study was to evaluate the radiation dose and response in terms of local-regional progression-free survival (LRPFS) and overall survival (OS) of patients with stage IV non-small cell lung cancer (NSCLC) undergoing concurrent chemotherapy and thoracic three-dimensional radiotherapy.MethodsIn all, we enrolled 201 patients with stage IV NSCLC in this study and analyzed OS in 159 patients and LRPFS in 120.ResultsThe 1-, 2-, 3-, and 5-year OS rates were 46.2%, 19.5%, 11.7%, and 5.8%, respectively, the median survival time being 12 months. The median survival times in differential treatment response of primary tumors were 19 of complete response, 13 of partial response, 8 of stable disease, and 6 months of progressive disease, respectively (P = 0.000). The 1-, 2-, 3-, and 5-year LRPFS rates of patients undergoing four to five cycles with doses ≥63 Gy and <63 Gy were 77.4% and 32.6%, 36.2% and 21.7%, 27.2% and 0, and 15.9% and 0, respectively (P = 0.002). According to multivariate analyses, four to five cycles of chemotherapy, gross tumor volume <175.00 cm3 and post-treatment Karnofsky Performance Status score stable or increased by at least 10 units were independent prognostic factors for better OS (P = 0.035, P = 0.008, and P = 0.000, respectively). Radiation dose to the primary tumor ≥63 Gy resulted in better OS (P = 0.057) and LRPFS (P = 0.051), both findings being of borderline significance.ConclusionsTreatment of IV NSCLC with joint administration of four to five cycles of chemotherapy and three-dimensional radiotherapy may prolong survival, particularly in patients receiving ≥63 Gy radiotherapy, with gross tumor volume <175.00 cm3 and post-treatment Karnofsky Performance Status score not lower than pretreatment values.

Management of Spontaneously Ruptured Hepatocellular Carcinomas in the Radiofrequency Ablation Era

Background and aimSpontaneous rupture of hepatocellular carcinoma (HCC) carries a high mortality. The use of radiofrequency ablation (RFA) in recent years has enriched the armamentarium for hemostasis of spontaneously ruptured HCCs but its results have not been documented. This study investigated the prognosis and outcome of spontaneous rupture of HCC as well as the results of using RFA for hemostasis.Patients and methodFrom January 1991 to December 2010, 5283 patients were diagnosed with HCC at our hospital, and 189 of them had spontaneous rupture of HCCs. They were grouped under two periods: period 1, 1991–2000, n = 70; period 2, 2001–2010, n = 119. RFA was available in period 2 only.ResultsHepatitis B virus infection was predominant in both periods. Surgical hemostasis was mainly achieved by hepatic artery ligation in period 1 and by RFA in period 2. The 30-day hospital mortality after surgical treatment was 55.6% (n = 18) in period 1 and 19.2% (n = 26) in period 2 (p = 0.012). Multivariate analysis identified 4 independent factors for better overall survival, namely, hemostasis by transarterial chemoembolization (hazard ratio 0.516, 95% confidence interval 0.354–0.751), hemostasis by RFA (hazard ratio 0.431, 95% confidence interval 0.236–0.790), having surgery as a subsequent treatment (hazard ratio 0.305, 95% confidence interval 0.186–0.498), and a serum total bilirubin level <19 umol/L (hazard ratio 1.596, 95% confidence interval 1.137–2.241).ConclusionThe use of RFA for hemostasis during laparotomy greatly reduced the hospital mortality rate when compared with conventional hepatic artery ligation.

Bortezomib-based chemotherapy for patients with multiple myeloma: a single center experience

To evaluate the efficacy and safety of bortezomib-based chemotherapy for 80 patients with multiple myeloma (MM). A total of 80 cases with a median age of 57 (range: 25-78) years were enrolled in the study. Bortezomib-based regimens included VD (bortezomib and dexamethasone) and PAD (bortezomib, doxorubicin and dexamethasone). 16 of the 80 patients received autologous or allo-hematopoietic stem cell transplantation (HSCT). The overall response (OR) rate was 80%, including a complete response (CR) of 46.3%. After a median follow-up of 25 months, the 1-year and 2-year overall survival (OS) was 81.4% and 72.9%, and the 2-year progression-free survival (PFS) was 76% and 62.5%, respectively. The 2-year OS and PFS were 100% and 73.9 % in patients with HSCT, while both were 66% (P=0.029) and 58.7% (P=0.447) in patients without HSCT. In univariate analysis, Durie-Salmon group, ISS stage, CR and very good partial response (VGPR), and HSCT were prognostic factors for OS. Gender and extramedullary plasmacytomas were important prognostic factors for PFS. Multivariate analysis by Cox regression revealed that CR and VGPR, Durie-Salmon group A, and HSCT were prognostic factors for better OS; while male and patients without extramedullary plasmacytomas were prognostic factors for longer PFS. MM patients could benefit from bortezomib-based chemotherapy with satisfactory efficacy and safety. HSCT could improve the OS for young MM patients.

Comparison of complete and minimal mediastinal lymph node dissection for non-small cell lung cancer: Results of a prospective randomized trial.

To compare surgical results, pathological staging, and survival between complete and minimal mediastinal lymph node dissection for non-small cell lung cancer (NSCLC). A randomized controlled trial was carried out in 202 patients who were assigned to undergo either skeletonized complete mediastinal lymph node dissection (CLD) or minimal mediastinal lymph node dissection (MLD). Clinical and pathological characteristics, surgical results, postoperative staging, and five-year survival were recorded for statistical analysis. Significantly more stations of lymph nodes were harvested through CLD, than MLD (8.9 vs. 6.2, P < 0.001). There was no difference in major complications (CLD 14.7% vs. MLD 14.0%, P = 0.884) or postoperative death (CLD 2.1% vs. MLD 1.9%, P = 0.904). No significant difference was detected in pathological staging between the two groups. The pN2 rates (27.1% vs. 24.2%), skip-mediastinal metastasis (9.3% vs. 7.4%), and multi-stational mediastinal involvement (15.0% vs. 16.8%) were similar between MLD and CLD. However, CLD had significantly better five-year survival than MLD (55.7% vs. 37.7%, P = 0.005), especially in patients with a tumor size >3 cm, pleural invasion, pN1-N2, stage II-III, adenocarcinoma, and low-differentiation carcinoma. Upon multivariate analysis, CLD, along with stage I and high-differentiation, were independent prognostic factors for better overall survival. Complete and minimal mediastinal dissections have similar surgical risks and mediastinal staging effect in patients with NSCLC. Minimal dissection is enough for early stage high-differentiation tumors. For patients with stage II-III or low-differentiation carcinoma, skeletonized complete mediastinal dissection may improve survival compared with minimal dissection.

Overall survival and toxicities regarding thoracic three-dimensional radiotherapy with concurrent chemotherapy for stage IV non-small cell lung cancer: results of a prospective single-center study

BackgroundThe role of chemotherapy given concurrently with thoracic three-dimensional radiotherapy for stage IV non-small cell lung cancer (NSCLC) is not well defined. We performed this study to investigate overall survival and toxicity in patients with stage IV NSCLC treated with this modality.MethodsFrom 2003 to 2010, 201 patients were enrolled in this study. All patients received chemotherapy with concurrent thoracic three-dimensional radiotherapy. The study endpoints were the assessment of overall survival (OS) and acute toxicity.ResultsFor all patients, the median survival time (MST) was 10.0 months, and the 1-, 2- and 3-year OS rates were 40.2%, 16.4%, and 9.6%, respectively. The MST was 14.0 months for patients who received a total radiation dose ≥63 Gy to the primary tumor, whereas it was 8.0 months for patients who received a total dose <63 Gy (P = 0.000). On multivariate analysis, a total dose ≥63 Gy, a single site of metastatic disease, and undergoing ≥4 cycles of chemotherapy were independent prognostic factors for better OS (P = 0.007, P = 0.014, and P = 0.038, respectively); radiotherapy involving metastatic sites was a marginally significant prognostic factor (P = 0.063). When the whole group was subdivided into patients with metastasis at a single site and multiple sites, a higher radiation dose to the primary tumor remained a significant prognostic factor for improved OS. For patients who received ≥4 cycles of chemotherapy, high radiation dose remained of benefit for OS (P = 0.001). Moreover, for the subgroup that received <4 chemotherapy cycles, the radiation dose was of marginal statistical significance regarding OS (P = 0.063). Treatment-related toxicity was found to be acceptable.ConclusionsRadiation dose to primary tumor, the number of metastatic sites, and the number of chemotherapy cycles were independent prognostic factors for OS in stage IV NSCLC patients treated with concurrent chemoradiotherapy. In addition to systemic chemotherapy, aggressive thoracic radiotherapy was shown to play an important role in improving OS.Trial registrationRegistered on (ChiCTR-TNC-10001026)

Are sarcomatoid lung cancers resistant tumors to conventional chemotherapy?

e19036 Background: Pulmonary sarcomatoid carcinomas (SC) account for about 0.4% of non-small cell lung carcinoma. These tumors have a poor prognosis due to high aggressiveness and maybe chemotherapy (CT) resistance. Methods: From 1995 to 2012, all consecutive patients with SC from 7 French hospitals and who underwent a 1st-line chemotherapy were included. Clinical characteristics and effect of CT (best response by RECIST 1.1 and progression-free survival [PFS]) as well as overall survival (OS) were collected. Results: Ninety-seven patients were included. Mean age was 62±1 years, 70% were men, 84% smokers, 84% symptomatic, 25% had a stage III and 75% a stage IV disease. At 1st-line, 73% received a platinum-based CT and 27% received a non-platinum-based CT. Progression (PR), stable disease (SD) and response (RR) rates were 69, 14.5 and 16.5%, respectively. For patients with platinum-based CT, PR, SD and RR rates were 69, 11 and 20%, respectively. RR rate was higher for platinum- than for non-platinum-based CT (p=0.018). Median PFS and OS were 2.0 mo [1.8 ; 2.3] and 6.7 mo [5.1 ; 8.2], respectively. No statistical difference in PFS (p=0.264) and OS (p=0.096) was observed between platinum and non-platinum based CT. In multivariate analysis, factors associated with better OS were disease control (HR=0.36 [0.21;0.59]), platinum-based CT (HR=0.92 [0.85;0.99]) and tobacco status (HR=0.92 [0.85 ; 0.99]). Conclusions: Two-thirds of patients with SC had early progression during 1st-line CT. Platinum-based regimen increased response rate for a few and was an independent factor for better OS with a 8% decreased risk of death. Overall, SC appear to be chemoresistant suggesting that new therapeutic strategies based on a better knowledge of its carcinogenesis should be tested for these patients.

Predictive value of 3′-deoxy-3′-[18F]fluorothymidine positron emission tomography/computed tomography for outcome of carbon ion radiotherapy in patients with head and neck mucosal malignant melanoma

The purpose of this prospective study was to assess the prognostic value of 3'-deoxy-3'-[(18)F]fluorothymidine (FLT) positron emission tomography/computed tomography (PET/CT) for the outcome of carbon ion radiotherapy (CIRT) in patients with mucosal malignant melanoma (MMM) of the head and neck. Thirteen patients (69 ± 13 years) with histologically proven MMM tumor were enrolled. CIRT was performed with a total dose of 57.6-64.0 gray equivalents per 16 fractions over a period of 4 weeks. FLT-PET/CT was performed before and again 1 month after CIRT. Tumor FLT uptake was quantitatively assessed using the maximum standardized uptake value (SUV(max)). FLT-PET parameters [pre-CIRT SUV(max), post-CIRT SUV(max), and the reduction rate (RR)] and clinical parameters [age, gender, tumor site, tumor status, gross tumor volume (GTV), and regional lymph node involvement] were evaluated in relation to survival estimates. The follow-up period was 16.1 ± 5.9 months for 9 deceased patients, and 36.7 ± 7.9 months for 4 survivors. Pre-CIRT SUV(max) of ≥4.3, age of ≥80 years old, sinonasal cavity tumor site, and GTV of ≥39 mL were found to be statistically significant prognostic factors for better overall survival. Pre-CIRT SUV(max) of ≥5.0, age of ≥80 years old, sinonasal cavity tumor site, and the absence of regional lymph node involvement were statistically significant prognostic factors for better metastasis-free survival. RR of ≥35 % and GTV of <73 mL were predictive of better local control. The present study indicated for the first time that in patients with the head and neck MMM, FLT-PET/CT imaging was useful for predicting the therapeutic outcome of CIRT. Our results will contribute to the establishment of an effective staging system for MMM based on prognostic factors, depending on treatment choice.

Skp2 expression unfavorably impacts survival in resectable esophageal squamous cell carcinoma.

BackgroundThe correlation of S-phase kinase–associated protein 2 (Skp2) with metastasis and prognosis in esophageal squamous cell carcinoma (ESCC) is controversial. The purpose of this study was to explore whether there was a correlation between the expression of Skp2 evaluated by immunohistochemistry and the clinical outcome of patients with operable ESCC, and to further determine the possible mechanism of the impact of Skp2 on survival.MethodsTissue microarrays that included 157 surgically resected ESCC specimens was successfully generated for immunohistochemical evaluation. The clinical/prognostic significance of Skp2 expression was analyzed. Kaplan-Meier analysis was used to compare the postoperative survival between groups. The prognostic impact of clinicopathologic variables and Skp2 expression was evaluated using a Cox proportional hazards model. A cell proliferation assay and a colony formation assay were performed in ESCC cell lines to determine the function of Skp2 on the progression of ESCC in vitro.ResultsSkp2 expression correlated closely with the T category (p = 0.035) and the pathological tumor-node-metastasis (TNM) stage (p = 0.027). High expression of Skp2 was associated with poor overall survival in resectable ESCC (p = 0.01). The multivariate Cox regression analysis demonstrated that pathological T category, pathological N category, cell differentiation, and negative Skp2 expression were independent factors for better overall survival. In vitro assays of ESCC cell lines demonstrated that Skp2 promoted the proliferative and colony-forming capacity of ESCCs.ConclusionsNegative Skp2 expression in primary resected ESCC is an independent factor for better survival. Skp2 may play a pro-proliferative role in ESCC cells.

Survival of patients with head and neck cancer

Prognostic factors (e.g., gender, tumor stage, and hypoxia) have an impact on survival in patients with head and neck cancer. Thus, the impact of physical status and comorbidities on treatment decision and survival were evaluated. A total of 169 primary, inoperable patients with squamous cell cancer of the head and neck were retrospectively investigated. Patients were treated with hyperfractionated accelerated radio(chemo)therapy (HARcT) or hypofractionated radio(chemo)therapy (HypoRcT). Depending on the individual patient's situation (Karnofsky Performance Index, KPI), treatment for patients with a KPI of 80-100% was generally radiochemotherapy and for patients with a KPI ≤ 70% treatment was radiotherapy alone. In addition, all comorbidities were evaluated. Uni- and multivariate proportional hazards model were used, and overall survival (OS) was estimated by the Kaplan-Meier method. Treatment consisted of HARcT for 76patients (45%), HART for 28patients (17%), HypoRcT for 14patients(8%), and HypoRT for 51patients (30%). Of the patients, 107patients (63%) presented with a KPI of 80-100%. OS (20%) was significantly better for patients with a KPI of 80-100%, while the OS for patients with a KPI ≤ 70% was 8% (p < 0.001). Good KPI, total irradiation dose (> 70Gy), and chemotherapy were significant prognostic factors for better OS. Our retrospective analysis shows that performance status with dependency on comorbidities was an independent risk factor for OS.

Clinicopathologic features and prognostic analysis of MSI-high colon cancer

The objectives of the study were to estimate the incidence and clarify the clinicopathologic feature of sporadic microsatellite instability (MSI)-high (MSI-H) colon cancer. Furthermore, the role of MSI in colon cancer prognosis was also investigated. Microsatellite status was identified by genotyping. The clinicopathologic differences between two groups (MSI-H vs. MSI-L/S) and the prognostic value of MSI were analyzed. From 1993 to 2006, 709 sporadic colon cancer patients were enrolled. MSI-H colon cancers showed significant association with poorly differentiated (28.3% vs. 7.2%, p = 0.001), proximally located (76.7% vs. 34.5%, p = 0.001), more high mucin-containing tumor (10.0% vs. 5.1%, p = 0.001) and female predominance (56.7% vs. 30.2%, p = 0.001). In multivariate analysis, MSI-H is an independent factor for better overall survival (HR, 0.459; 95% CI, 0.241-0.872, p = 0.017). Based on the hospital-based study, MSI-H colon cancers demonstrated distinguished clinicopathologic features from MSI-L/S colon cancers. MSI-H is an independent favorable prognostic factor for overall survival in colon cancer.

The Glasgow Prognostic Score Is a Good Predictor of Treatment Outcome in Patients with Unresectable Pancreatic Cancer

Background: We analyzed the outcome of patients with advanced unresectable pancreatic cancer treated in our department from 2001 to 2008. Methods: Of the 83 patients included in this study, 50 patients received single-agent treatment with gemcitabine (GEM), 9 patients GEM combined with radiotherapy (GEM+R) and 24 patients had best supportive care (BSC). We analyzed survival rates among the groups and risk factors for each group. Results: The 3-year survival rates were dismal: GEM group 2.9%, GEM+R group 0% and BSC group 0%. Significant prognostic factors of the study were: performance status (PS), response rate and decrease in the CA19-9 level. Significant prognostic factors by the Cox proportional hazard model were the albumin level prior to treatment, CA19-9 levels before treatment, decrease in CA19-9 and response rate. Albumin levels and the Glasgow Prognostic Score (GPS) were found to be factors affecting survival in the GEM group. Conclusion: In this series of patients with unresectable pancreatic cancer, good PS, decrease in CA19-9 after treatment and good GPS determined prior to treatment were independent prognostic factors for better overall survival.