Significant Prognostic Factor For Progression-free Survival Research Articles

Prognostic impact of serum soluble interleukin-2 receptor level at diagnosis in elderly patients with diffuse large B-cell lymphoma treated with R-CHOP

Diffuse large B-cell lymphoma (DLBCL) is a clinically heterogeneous disease. To evaluate the clinical relevance of the serum soluble interleukin-2 receptor (sIL-2R) level, we retrospectively analyzed 178 patients aged ≥60 years who were newly diagnosed with DLBCL. We determined the cutoff value of the sIL-2R level to be 1280 U/mL using the area under the receiver operating characteristic curve. The high sIL-2R group exhibited significantly inferior 5-year progression-free survival (PFS) (36.2% vs. 86.1%, p < .001) and 5-year overall survival (OS) (49.7% s. 83.8%, p < .001) than the low sIL-2R group. Multivariate analysis revealed that a high sIL-2R level was a significant prognostic factor for PFS and OS (hazard ratio [HR]: 5.65, p < .001 and HR: 2.99, p = .001, respectively). This study showed that measurement of the sIL-2R level at diagnosis is clinically beneficial for identifying elderly patients with DLBCL who have a poor prognosis.

Real-world data on Len/Dex combination at second-line therapy of multiple myeloma: treatment at biochemical relapse is a significant prognostic factor for progression-free survival

We evaluated progression-free survival (PFS) rate of patients treated with lenalidomide/dexamethasone (Len/Dex), the efficacy of the combination, and the prognostic significance of treatment at biochemical vs. clinical relapse on PFS in 207 consecutive myeloma patients treated with Len/Dex in second line, according to routine clinical practice in Greece. First-line treatment included bortezomib-based (63.3%) or immunomodulatory drug-based (34.8%) therapies; 25% of patients underwent autologous stem cell transplantation. Overall response rate was 73.4% (17.8% complete response and 23.7% very good partial response); median time to best response was 6.7 months. Overall, median PFS and 12-month PFS rate was 19.2 months and 67.6%, respectively. 67.5% of patients had biochemical relapse and 32.5% had clinical relapse prior to initiation of Len/Dex. Median PFS was 24 months for patients treated at biochemical relapse vs. 13.2 months for those treated at clinical relapse (HR:0.63, p = 0.006) and the difference remained significant after adjustment for other prognostic factors. Type of relapse was the strongest prognostic factor for PFS in multivariate analysis. These real-world data confirm the efficacy of Len/Dex combination at first relapse; more importantly, it is demonstrated for the first time outside a clinical trial setting that starting therapy with Len/Dex at biochemical, rather than at clinical relapse, is a significant prognostic factor for PFS, inducing a 37% reduction of the probability of disease progression or death.

Abstract P3-05-09: Prognostic factors for therapeutic personalized peptide vaccines in patients with metastatic recurrent breast cancer

Abstract Background: We have previously reported the prognostic role of humoral antigen spreading response against prostate-related antigen (PRA) for metastatic recurrent breast cancer (mrBC) patients who received personalized peptide vaccine (PPV) therapy (Toh U, SABCS 2015). The prognostic effect was additionally evaluated by the clinical relevant factors including intrinsic subtype, the regimens of combined chemo-hormonal therapies in present study. Methods:We analyzed serum IgG responses to all of the peptide candidates included PRAs (PSA, PAP and PMSA) after PPV therapy by the Luminex systemusing peripheral blood samples from 77 vaccinated mrBC patients. The clinical factors and relevant events were statistically evaluated. Results: After 6 and 12cycles of PPV therapy, the serum IgG of anti-PSA, anti-PAP, and/or anti-PMSA increased significantly in 31 patients (PRA response group), and the median progression free survival (PFS) and median overall survival (OS) were 8.1 and 14.3 months, but were 5.1 and 10.8 months, respectively, in the remaining 46 patients with no anti-PRA IgG response (PRA non-response Group). The anti-PRA IgG level was marginally correlated withPFS (p=0.059) and OS (p=0.082) between these two groups, which was a significant prognostic factor for PFS (Log-rank: 0.009) in estrogen-positive cancer patients (ER+). The statistical analyses showed that the clinical outcome was in favor of &amp;gt; 60 year-old patients, those with longer PPV therapies (&amp;gt;3 months), and those who received combined standard hormonal therapies or bisphosphonate/anti-RANKL therapy. Conclusions: This study indicated a clinical significance between the pre-and post- PPV therapy measurement of serum anti-PRA IgG in patients with mrBC, which may be a useful prognostic marker for monitoring peptide vaccine treatment outcomes, particularly for patients &amp;gt; 60 years with ER+ breast cancer. These results also suggest that the immunotherapeutic peptide vaccine could be efficiently combined with hormonal therapy, anti-HER2 therapy, and bisphosphonate/anti-RANKL therapy in mrBC patients. Citation Format: Toh U, Saku S, Iwakuma N, Takao Y, Okabe M, Akashi M, Yamada A, Shichijo S, Itoh K, Akagi Y. Prognostic factors for therapeutic personalized peptide vaccines in patients with metastatic recurrent breast cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P3-05-09.

Prognostic Factors in Patients With Spinal Chordoma: An Integrative Analysis of 682 Patients.

The low incidence of spinal chordoma precludes a prospective study of prognostic factors with a large patient cohort. To perform a comprehensive integrative analysis on the prognostic factors, treatment, and outcomes of patients with spinal chordoma using data from 2 institutions and the literature. Appropriate studies were identified per search criteria. The local database was retrospectively searched to include a similar patient cohort. Overall, 108 studies from the literature and 30 patients from our local institution were identified, resulting in a total of 682 patients. The median age was 57 years old and 35.2% were female. The median follow-up was 46 months (range: 1-408). The median progression-free survival (PFS) and overall survival (OS) were 72 months and 115 months, respectively. Significant prognostic factors for PFS on multivariate analysis included age (pediatric vs adult, hazard ratio [HR]: 2.00-14.36), tumor location (mobile spine vs sacral spine, HR: 0.31-0.87), pathology (differentiated vs classic, HR: 2.48-10.90),and chemotherapy (HR:1.11-3.85). Significant prognostic factors for OS on multivariate analysis included age (geriatric vs adult, HR: 1.52-3.45 and pediatric vs adult, HR: 1.73-9.36), bladder or bowel dysfunction (HR: 1.27-5.43), pathology (dedifferentiated vs classic, HR: 2.38-11.09), recurrence or progression (HR: 1.72-4.48), and metastases (HR: 1.11-2.47). In patients with spinal chordoma, young age, location in sacral spine, dedifferentiated pathology, and chemotherapy were negative predictors of PFS, while young and old age, bladder or bowel dysfunction at presentation, dedifferentiated pathology, recurrence or progression, and metastases portended a worse OS.

Kinetics of HE4 and CA125 markers in metastatic ovarian cancer: The META4 study.

e17059 Background: HE4 is a new marker that could improve the detection of ovarian cancer (OC). The objective of the present study was to compare the prognostic value of the HE4 and CA125 markers in patients (pts) with metastatic epithelial OC, considering the progression-free survival (PFS). Methods: 101 pts, treated with 2nd/3rd line of chemotherapy, were included in 3 cancer centers between 2010 and 2014. Serums were prospectively collected before the 1stchemotherapy cycle, during chemotherapy and every 3 months until disease progression. The primary endpoint was HE4 and CA125 marker level evolution under treatment. Secondary endpoints were the markers’ main kinetic parameters: initial concentration, nadir, time to nadir, time to normalisation, half-life, doubling time and time to exceed the clinical threshold (CA125≥35UI/L; HE4≥75pM) (NCT01768156). Results: 89 pts were included in the final analysis. Median age was 65 (34-83). Histological sub-types were mainly serous (88%). The median PFS was 45 weeks (95%CI: 33.4-52). At baseline, median CA125 and HE4 levels were 210UI/L (7-10310) and 184pM (31-4836), respectively. Among 12 pts (13%) CA125- (with CA125 &lt; 35UI/L), 8 were HE4+ (with HE4≥75pM) and among 16 pts (18%) HE4-, 12 were CA125+. The median nadir was 31UI/L (3-8744) for CA125 and 75pM (20-4836) for HE4. Median time to nadir was 14 (0-130) and 12 weeks (0-52) for CA125 and HE4, respectively. The median time to normalization was 17 (3-247) and 17 weeks (2-203) for CA125 and HE4, and the median half-life was 8 (1-193) and 12 weeks (2-166), respectively. The median doubling time and the time to exceed the clinical threshold were respectively of 13.5 and 40.2 weeks for CA125, and 23 and 23.6 weeks for HE4. In multivariate analysis, the CA125 nadir ( &lt; 35 vs ≥35: HR = 3.13; 95%CI: 1.75-5.58), CA125 time to nadir ( &lt; 14 vs ≥14: HR = 0.46, 95%CI: 0.28-0.76), HE4 nadir ( &lt; 75 vs ≥75: HR = 1.95; 95%CI 1.16-3.27), and HE4 time to nadir ( &lt; 12 vs≥12: HR = 0.39; 95%CI: 0.23-0.67) were found significant prognostic factors for PFS. Conclusions: Nadir and time to nadir were significant for both HE4 and CA125 markers in multivariate analysis. Further investigations on HE4 kinetic could be helpful for monitoring pts presenting no variation of CA125. Clinical trial information: NCT01768156.

Clinical significance of circulating tumor cells in patients with small-cell lung cancer.

This study investigated the correlation of the presence of circulating tumor cells (CTCs) with clinical characteristics, and the predictive value of CTCs for progression-free survival (PFS) in patients with small-cell lung cancer (SCLC). Samples were obtained from 42 patients with SCLC before and after the first cycle of chemotherapy. CTCs were quantitated by negative immunomagnetic enrichment and immunocytochemistry using anti-CD45 and anti-pancytokeratin antibodies. CTCs were positive (≥2) in 76.19% of patients with SCLC and negative in the control group. The presence of CTCs was positively correlated with 6 clinical characteristics. PFS was 6.055 and 10.670 months for patients with ≥2 and <2 CTCs/7.5 mL of blood before chemotherapy; after chemotherapy PFS was 4.862 and 10.535 months, respectively. This study showed that both baseline CTC numbers and the change in CTC numbers after 1 cycle of chemotherapy are significant prognostic factors of PFS for SCLC.

Primary Tumor Characteristics Are Important Prognostic Factors for Sorafenib-Treated Patients with Metastatic Renal Cell Carcinoma: A Retrospective Multicenter Study.

We aimed to identify prognostic factors associated with progression-free survival (PFS) and overall survival (OS) in metastatic renal cell carcinoma (mRCC) patients treated with sorafenib. We investigated 177 patients, including 116 who received sorafenib as first-line therapy, using the Cox regression model. During a median follow-up period of 19.2 months, the PFS and OS were 6.4 and 32.6 months among all patients and 7.4 months and undetermined for first-line sorafenib-treated patients, respectively. Clinical T3-4 stage (hazard ratio [HR] 2.56) and a primary tumor size >7 cm (HR 0.34) were significant prognostic factors for PFS among all patients, as were tumor size >7 cm (HR 0.12), collecting system invasion (HR 5.67), and tumor necrosis (HR 4.11) for OS (p < 0.05). In first-line sorafenib-treated patients, ≥4 metastatic lesions (HR 28.57), clinical T3-4 stage (HR 4.34), collecting system invasion (univariate analysis HR 2.11; multivariate analysis HR 0.07), lymphovascular invasion (HR 13.35), and tumor necrosis (HR 6.69) were significant prognosticators of PFS, as were bone metastasis (HR 5.49) and clinical T3-4 stages (HR 4.1) for OS (p < 0.05). Our study thus identified a number of primary tumor-related characteristics as important prognostic factors in sorafenib-treated mRCC patients.

β-Elemene treatment of glioblastoma: a single-center retrospective study.

Glioblastoma (GBM) is the most common primary malignancy in the central nervous system. In this study, we investigated the therapeutic effects of β-elemene (ELE) treatment in patients with newly diagnosed GBM who received concomitant chemoradiotherapy and adjuvant chemotherapy with temozolomide. Our results indicated that compared with control, patients who received ELE showed significantly longer median progression-free survival (PFS) (8 months vs 11 months; P<0.001) and overall survival (OS) (18 months vs 21 months; P<0.001). Despite the O-6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status, ELE treatment could significantly prolong the PFS (P=0.038) and OS (P=0.016). In multivariate analysis, ELE was a significant prognostic factor for PFS (hazard ratio [HR], 0.34; 95% confidence interval [95% CI]: 0.15–0.62; P=0.011) and OS (HR, 0.31; 95% CI: 0.14–0.69; P=0.006). Furthermore, ELE could significantly reduce the hematologic toxicities induced by chemoradiotherapy. In conclusion, ELE might provide a survival benefit in patients with GBM. Further study for verification might be needed.

982P - Metronomic oral cyclosphosphamide as 3rd line systemic treatment or beyond in patients with inoperable locoregionally advanced recurrent or metastatic nasopharyngeal carcinoma

There is no standard 3rd line or further systemic treatment for patients inoperable locoregionally advanced recurrent/metastatic nasopharyngeal carcinoma (NPC). Oral cyclophosphamide provides a convenient and cheap option for these heavily pretreated patients who have very limited choices of treatment options. We conducted a prospective single-arm open-label study of metronomic oral cyclophosphamide in this setting. Patients with locoregionally advanced recurrent inoperable (rT3/T4, rN2-N3b) or metastatic (rM1) NPC who had good ECOG performance status (PS) (0-2) and had progressed after at least 2 lines of palliative systemic chemotherapy were eligible. They received open-label oral cyclophosphamide between 50mg to 150mg daily dose. Best objective response rate (ORR), disease control rate (DCR), biochemical response assessed by plasma EBV DNA, progression-free survival (PFS), overall survival (OS) and safety profiles were evaluated. Of 56 patients who received cyclophosphamide, 16 and 37 (66.1%) had ECOG performance status (PS) 1 and 2 respectively. 33, 13, 6, 3 and 1 patients received cyclophosphamide as 3rd, 4th, 5th, 6th and 7th line of therapy respectively. After a median follow-up of 8.95 months (range 0.76-58.51), the ORR was 8.9% and the DCR was 57.1% after cyclophosphamide. Biochemical response with 2 consecutive decline in plasma EBV DNA was seen in 10 (17.9%) patients. The median PFS and OS were 4.47 and 9.20 months. Those with PS 1 had a longer median PFS (5.49 months) compared to those with PS 2 (3.75 months, p = 0.011). Univariable (p = 0.021) and multivariable analysis (p = 0.010) revealed that ECOG PS 1 was the only significant prognostic factor of PFS. 16 (28.6%) patients developed 3G3 adverse events, including malaise (5.4%), haematological (8.9%), gastrointestinal (3.6%) and feverish (3.6%) and hemorrhagic (1.8%) events. The median cost of the whole drug treatment was 51.65 USD (1 USD = 7.8 HKD). Oral cyclophosphamide is an acceptable 3rd line or subsequent line systemic therapy for locoregionally advanced recurrent or metastatic NPC with acceptable toxicity and limited financial burden to patients.

Comparative evaluation of SUV, tumor-to-blood standard uptake ratio (SUR), and dual time point measurements for assessment of the metabolic uptake rate in FDG PET.

BackgroundWe have demonstrated recently that the tumor-to-blood standard uptake ratio (SUR) is superior to tumor standardized uptake value (SUV) as a surrogate of the metabolic uptake rate Km of fluorodeoxyglucose (FDG), overcoming several of the known shortcomings of the SUV approach: excellent linear correlation of SUR and Km from Patlak analysis was found using dynamic imaging of liver metastases. However, due to the perfectly standardized uptake period used for SUR determination and the comparatively short uptake period, these results are not automatically valid and applicable for clinical whole-body examinations in which the uptake periods (T) are distinctly longer and can vary considerably. Therefore, the aim of this work was to investigate the correlation between SUR derived from clinical static whole-body scans and Km-surrogate derived from dual time point (DTP) measurements.MethodsDTP 18F-FDG PET/CT was performed in 90 consecutive patients with histologically proven non-small cell lung cancer (NSCLC). In the PET images, the primary tumor was delineated with an adaptive threshold method. For determination of the blood SUV, an aorta region of interest (ROI) was delineated manually in the attenuation CT and transferred to the PET image. Blood SUV was computed as the mean value of the aorta ROI. SUR values were computed as ratio of tumor SUV and blood SUV. SUR values from the early time point of each DTP measurement were scan time corrected to 75 min postinjection (SURtc). As surrogate of Km, we used the SUR(T) slope, Kslope, derived from DTP measurements since it is proportional to the latter under the given circumstances. The correlation of SUV and SURtc with Kslope was investigated. The prognostic value of SUV, SURtc, and Kslope for overall survival (OS) and progression-free survival (PFS) was investigated with univariate Cox regression in a homogeneous subgroup (N=31) treated with primary chemoradiation.ResultsCorrelation analysis revealed for both, SUV and SURtc, a clear linear correlation with Kslope (P<0.001). Correlation SUR vs. Kslope was considerably stronger than correlation SUV vs. Kslope (R2=0.92 and R2=0.69, respectively, P<0.001). Univariate Cox regression revealed SURtc and Kslope as significant prognostic factors for PFS (hazard ratio (HR) =3.4/ P=0.017 and HR =4.3/ P=0.020, respectively). For SUV, no significant effect was found. None of the investigated parameters was prognostic for OS.ConclusionsScan-time-corrected SUR is a significantly better surrogate of tumor FDG metabolism in clinical whole-body PET compared to SUV. The very high linear correlation of SUR and DTP-derived Kslope (which is proportional to actual Km) implies that for histologically proven malignant lesions, FDG-DTP does not provide added value in comparison to the SUR approach in NSCLC.

Percutaneous computed tomography-guided cryoablation for recurrent retroperitoneal soft tissue sarcoma: a study of safety and efficacy.

AimsTo evaluate the use of computed tomography image-guided percutaneous cryoablation for recurrent retroperitoneal soft tissue sarcomas (RPSs).ResultsAdverse events were limited to grades 1 and 2, included fever (n = 19), local pain (n = 11), emesis (n = 10), frostbite (n = 6), and nerve injury (n = 1). Fever was more frequent in the large tumor group (15.8%) than in small tumor group (1.9%) (P = 0.008). Median PFS and OS were 37.0 ± 7.7 months (range, 4–39 months) and 43.0 ± 5.9 months (range, 6–54 months), respectively. PFS and OS were significantly longer in the small tumor group than in the large tumor group (P = 0.011 and P = 0.015, respectively), but the response rate (82.7% vs. 72.8%, P = 0.240) did not differ significantly. On univariate analysis, tumor size, tumor invasion grade, and distant metastasis were significant prognostic factors for PFS and OS. On multivariate analysis, a tumor size ≥10 cm was an independent negative prognostic factor for PFS and OS after cryoablation (HR: 3.98, 95% CI: 1.27–12.50, P = 0.018 and HR: 4.33, 95% CI: 1.41–13.26, P = 0.010, respectively).Materials and MethodsData from 72 patients with recurrent RPSs who underwent percutaneous cryoablation were reviewed retrospectively. The prognostic factors for progression-free survival (PFS), overall survival (OS), and efficacy based on mRECIST criteria were analysis. Adverse events were compared according to tumor size (<10 and ≥10 cm).ConclusionMinimally invasive percutaneous cryoablation was safe and efficacious for recurrent RPSs.

Prognostic value of the standardized uptake value maximum change calculated by dual-time-point (18)F-fluorodeoxyglucose positron emission tomography imaging in patients with advanced non-small-cell lung cancer.

PurposeThe purpose of this study was to investigate the prognostic value of the standardized uptake value maximum (SUVmax) change calculated by dual-time-point 18F-fluorodeoxyglucose positron emission tomography (PET) imaging in patients with advanced non-small-cell lung cancer (NSCLC).Patients and methodsWe conducted a retrospective review of 115 patients with advanced NSCLC who underwent pretreatment dual-time-point 18F-fluorodeoxyglucose PET acquired at 1 and 2 hours after injection. The SUVmax from early images (SUVmax1) and SUVmax from delayed images (SUVmax2) were recorded and used to calculate the SUVmax changes, including the SUVmax increment (ΔSUVmax) and percent change of the SUVmax (%ΔSUVmax). Progression-free survival (PFS) and overall survival (OS) were determined by the Kaplan–Meier method and were compared with the studied PET parameters, and the clinicopathological prognostic factors in univariate analyses and multivariate analyses were constructed using Cox proportional hazards regression.ResultsOne hundred and fifteen consecutive patients were reviewed, and the median follow-up time was 12.5 months. The estimated median PFS and OS were 3.8 and 9.6 months, respectively. In univariate analysis, SUVmax1, SUVmax2, ΔSUVmax, %ΔSUVmax, clinical stage, and Eastern Cooperative Oncology Group (ECOG) scores were significant prognostic factors for PFS. Similar results were significantly correlated with OS, except %ΔSUVmax. In multivariate analysis, ΔSUVmax and %ΔSUVmax were significant factors for PFS. On the other hand, ECOG scores were only identified as independent predictors of OS.ConclusionOur results demonstrated the prognostic value of the SUVmax change in predicting the PFS of patients with advanced NSCLC. However, SUVmax change could not predict OS.

Leksell Gamma Knife treatment for pilocytic astrocytomas: long-term results.

OBJECTIVE The purpose of this study was to evaluate long-term treatment results, radiation-related toxicity, and prognostic factors for the progression-free survival (PFS) of patients with pilocytic astrocytomas treated by means of stereotactic radiosurgery with a Leksell Gamma Knife. METHODS A total of 25 patients with pilocytic astrocytomas underwent Gamma Knife surgery during the period 1992-2002. The median target volume was 2700 mm(3) (range 205-25,000 mm(3)). The 18 patients treated with 5 daily fractions received a median minimum target dose of 25 Gy. Doses for the 2 patients treated with 10 fractions over 5 days (2 fractions delivered on the same day at least 6 hours apart) were 23 and 28 Gy. For the 5 patients treated with a single fraction, the minimum target dose ranged from 13 to 20 Gy (median 16 Gy). RESULTS Complete regression occurred in 10 patients (40%) and partial regression in 10 patients (40%). The 10-year overall survival rate was 96% and the 10-year PFS rate was 80%. Target volume appeared to be a significant prognostic factor for PFS (p = 0.037). Temporary Grade 3 toxicity appeared in 2 patients (8%), and these patients were treated with corticosteroids for 2 months. Permanent Grade 4 toxicity appeared in 2 patients (8%) and was associated with neurocognitive dysfunction. In these 2 individuals, the neurocognitive dysfunction was also felt to be in part the result of the additional therapeutic interventions (4 in one case and 6 in the other) required to achieve durable control of their tumors. CONCLUSIONS Radiosurgery represents an alternative treatment modality for small residual or recurrent volumes of pilocytic astrocytomas and provides long-term local control. Target volume appears to be the most important factor affecting PFS.

The Highest Metabolic Activity on FDG PET Is Associated With Overall Survival in Limited-Stage Small-Cell Lung Cancer.

We evaluated the prognostic value of 18F-fluorodeoxyglucose positron emission tomography (FDG PET) parameters for limited-stage small-cell lung cancer (LS-SCLC).We retrospectively enrolled 59 LS-SCLC patients who underwent pretreatment FDG PET/CT. Various PET parameters were measured in all malignant lesions, and we recorded the highest maximum standardized uptake value (SUVmax), and sum of metabolic tumor volume (MTVsum) and total lesion glycolysis (TLGsum). The relationship between the highest SUVmax and volumetric PET parameters was evaluated. The prognostic significances of PET parameters and clinical variables were assessed using Cox's proportional hazard regression analysis. Overall survival (OS) and progression-free survival (PFS) were assessed by the Kaplan–Meier method.The SUVmax of the highest metabolic lesion had a significant positive correlation with MTVsum and TLGsum (P < 0.001). Upon multivariate analysis, the highest SUVmax was an independent predictor of OS (1 unit increase, hazard ratio [HR]: 1.133, P = 0.003) and MTVsum was a significant prognostic factor of PFS (10-cm3 increase, HR: 1.027, P = 0.034) after adjusting for age, sex, performance status, tumor stage, and treatment modality. The highest SUVmax was a prognostic factor for PFS with marginal significance (1 unit increase, HR: 1.078, P = 0.053). Patients with higher SUVmax (≥11) were also characterized by a significantly shorter median OS (P < 0.001) and PFS (P = 0.002) compared with patients with lower SUVmax.The highest SUVmax is an independent prognostic factor for survival in LS-SCLC patients. Therefore, the highest SUVmax might be a possible imaging biomarker for risk stratification in LS-SCLC. A further study in a large cohort is needed to validate the prognostic significance of the parameter.

Outcomes of Young Patients With Rectal Cancer From a Tertiary Cancer Care Centre in India

BackgroundCarcinoma of the rectum is the fourth most common cancer in the world. The peak age of diagnosis is around the seventh decade. Rectal cancer presenting in those < 35 years old are very peculiar in that they present with adverse histologic features and more advanced stage compared with rectal cancer presenting in older patients. Materials and MethodsWe retrospectively evaluated the patient records of young patients with rectal cancer (aged < 35 years) treated in our unit at the All India Institute from 2007 to 2013. ResultsA total of 60 young patients with rectal cancer were registered in our unit during the study period. A family history of cancer was present in 3 patients. The median age at presentation was 27.5 years (range, 15-34 years). The male-to-female ratio was 1.5:1. Of the 60 patients, 52 (86.6%) presented with advanced-stage disease (stage III and IV). Mucinous, signet, papillary, and other poor-risk histologic features were seen in 33 patients (55%). The treatment intention was radical for 50 patients (83.3%). The median follow-up period was 7.3 months. Eighteen patients had documented disease progression. Distant metastasis was the most common type of failure, seen in 14 of 18 patients (77%). The median progression-free survival (PFS) was 1.4 years. The 1- and 3-year PFS rates were 66.5% and 42.0%, respectively. On univariate analysis, the Karnofsky performance status and histologic type were significant prognostic factors for PFS. ConclusionA greater proportion of poor histologic subtypes was found among young patients with rectal cancer. The high incidence of poor histologic subtypes confers a poor prognosis in these patients.

Prognostic value of negative interim 2-[18F]-fluoro-2-deoxy-d-glucose PET/CT in diffuse large B-cell lymphoma

To assess the prognostic value of negative interim combined 2-[(18)F]-fluoro-2-deoxy-d-glucose ((18)F-FDG) positron-emission tomography/computed tomography (PET/CT) in patients with diffuse large B-cell lymphoma (DLBCL). Ninety-two patients with histologically proven DLBCL were enrolled. All of the patients underwent (18)F-FDG PET/CT at diagnosis, and interim PET/CT after the second cycle of chemotherapy with rituximab, cyclophosphamide, hydroxydaunorubicin, vincristine, and prednisolone (R-CHOP). Negative interim PET/CT was defined as the disappearance of all abnormal (18)F-FDG uptake compared to the pretreatment PET/CT image, as determined by visual assessment. The clinical outcome of patients was estimated as progression-free survival (PFS), and the prognostic significance of clinicopathological and imaging parameters were assessed using the Cox proportional hazards model. Thirty-six patients (39.1%) showed lymphoma progression within a median follow-up of 30.8 months. According to univariate analysis, Ann Arbor stage, serum lactate dehydrogenase level, Eastern Cooperative Oncology Group scale, International Prognostic Index (IPI) score, and maximum standardised uptake values on initial PET/CT were significant prognostic factors for PFS (all p<0.05). Among these parameters, only the IPI score was an independent predictor for PFS (p=0.044). Survival of patients with a high IPI score (≥3) was poorer than those with a low IPI score (0-2; p<0.001). Despite a negative interim (18)F-FDG PET/CT, approximately 39% of DLBCL patients showed progression during follow-up. Although the negative PET/CT was obtained during chemotherapy, it is important to closely follow-up patients, especially those with a high IPI score.

The Presence of M Protein Is Strongly Associated with Very Poor Prognosis in Patients with Extranodal Diffuse Large B-Cell Lymphoma

IntroductionSeveral studies concerning extranodal diffuse large B-cell lymphoma (DLBCL) have been reported sporadically. However, no new, valuable prognostic factors have been reported since several risk factors, such as a high international prognostic index (IPI) score, elevated lactate dehydrogenase (LDH) level, poor Eastern Cooperative Oncology Group (ECOG) performance status (PS), advanced stage, and extranodal sites ≥2, were identified.MethodsTo identify new and valuable prognostic factors, we reviewed the medical records of patients with nodal and extranodal DLBCL who were newly diagnosed at the Cancer Institute Hospital of the Japanese Foundation for Cancer Research from February 2005 to September 2014, and retrospectively analyzed the data of a total of 463 consecutive DLBCL patients. The cases were nodal DLBCL in 237 patients and extranodal DLBCL in 226 patients. We investigated the relationships between overall survival (OS), progression-free survival (PFS), and age, gender, LDH level, beta-2 microglobulin level (b2MG), performance status (PS), stage, extranodal sites ≥2, Ki-67 index, and M protein in serum protein fraction electrophoresis at diagnosis. Univariate and multivariate analyses of estimated risk factors for OS and PFS in extranodal DLBCL patients were performed using the log-rank test and Cox proportional hazard regression analysis.ResultsIn patients with extranodal DLBCL, the median age was 67 years (range, 20-89 years). The median follow-up was 41 months (range, 1-115 months). A serum electrophoresis study detected M protein in 7 patients (3.1%). To adjust the impact of age, gender, LDH level, b2MG, PS, stage, extranodal sites ≥2, Ki-67 index, and the presence of M protein in serum protein fraction electrophoresis at diagnosis for other significant factors for OS, we identified the following risk factors in extranodal DLBCL by univariate analysis: elevated LDH level, elevated b2MG level, stage ≥3, extranodal sites ≥2, and the presence of M protein. Then, we performed multivariate analyses by using all of these factors in the Cox proportional hazard model. M protein (HR 6.78, 95% CI 2.19-20.96, P<0.001) and extranodal sites ≥2 (HR 3.71, 95% CI 1.77-7.80, P<0.001) were identified as independent significant prognostic factors for OS in extranodal DLBCL. Furthermore, we also identified M protein (HR 3.81, 95% CI 1.25-11.60, P=0.019) and extranodal sites ≥2 (HR 2.98, 95% CI 1.45-6.14, P=0.003) as independent significant prognostic factors for PFS by multivariate analysis. Four out of seven patients with M protein died due to lymphoma progression. Median overall survival in patients with extranodal DLBCL with M protein was 12 months (range, 2-114 months) compared with 44 months without M protein (range, 1-115 months, P=0.0038). On the other hand, in patients with nodal DLBCL, M protein (n=10) was not significantly associated with poor OS and PFS.ConclusionsThese results suggest that the presence of M protein in serum protein fraction electrophoresis is significantly associated with very poor OS and PFS in patients with extranodal DLBCL, but not nodal DLBCL. Extranodal DLBCL with M protein is a rare and very poor prognostic subset of DLBCL. [Display omitted] DisclosuresYokoyama:Chugai Pharmaceutical CO., LTD.: Consultancy. Mishima:Chugai Pharmaceutical CO., LTD.: Consultancy. Nishimura:Chugai Pharmaceutical CO., LTD.: Consultancy. Hatake:Chugai Pharmaceutical CO., LTD.: Other: lecture speaking.

Prognostic Value of Metabolic Tumor Volume on (11)C-Methionine PET in Predicting Progression-Free Survival in High-Grade Glioma.

C-11 methionine (MET) PET is commonly used for diagnosing high-grade glioma (HGG). Recently, volumetric analysis has been widely applied to oncologic PET imaging. In this study, we investigated the prognostic value of metabolic tumor volume (MTV) on MET PET in HGG. A total of 30 patients with anaplastic astrocytoma (n = 12) and glioblastoma multiforme (n = 18) who underwent MET PET before treatment (surgery followed by chemo-radiotherapy) were retrospectively enrolled. Maximal tumor-to-normal brain ratio (TNRmax, maximum tumor activity divided by mean of normal tissue) and MTV (volume of tumor tissue that shows uptake >1.3-fold of mean uptake in normal tissue) were measured on MET PET. Adult patients were classified into two subgroups according to Radiation Therapy Oncology Group Recursive Partitioning Analysis (RTOG RPA) classification. Prognostic values of TNRmax, MTV and clinicopathologic factors were evaluated with regard to progression-free survival (PFS). Median PFS of all patients was 7.9months (range 1.0-53.8months). In univariate analysis, MTV (cutoff 35cm(3)) was a significant prognostic factor for PFS (P = 0.01), whereas TNRmax (cutoff 3.3) and RTOG RPA class were not (P = 0.80 and 0.61, respectively). Treatment of surgical resection exhibited a borderline significance (P = 0.06). In multivariate analysis, MTV was the only independent prognostic factor for PFS (P = 0.03). MTV on MET PET is a significant and independent prognostic factor for PFS in HGG patients, whereas TNRmax is not. Thus, performing volumetric analysis of MET PET is recommended in HGG for better prognostication.

The Prognostic Value of Plasma Epstein-Barr Viral DNA and Tumor Response to Neoadjuvant Chemotherapy in Advanced-Stage Nasopharyngeal Carcinoma

To explore the prognostic value of the plasma load of Epstein-Barr viral (EBV) DNA and the tumor response to neoadjuvant chemotherapy (NACT) in advanced-stage nasopharyngeal carcinoma (NPC). In all, 185 consecutive patients with stage III to IVb NPC treated with NACT followed by concurrent chemoradiation therapy (CCRT) were prospectively enrolled. The primary endpoint was progression-free survival (PFS), and the secondary endpoints included locoregional relapse-free survival (LRFS) and distant metastasis-free survival (DMFS). EBV DNA was detected in 165 (89%) patients before treatment but was undetectable in 127 (69%) patients after NACT. Detectable EBV DNA levels after NACT were correlated with poor prognosis (3-year PFS 71.8% vs 85.2%, P=.008 and 3-year DMFS 82.5% vs 92.3%, P=.013). An unsatisfactory tumor response (stable disease or disease progression) after NACT was also correlated with poor clinical outcome (3-year PFS 71.1% vs 85.9%, P=.005 and 3-year LRFS 82.7% vs 93.5%, P=.012). Multivariate analysis showed that the EBV DNA level after NACT (hazard ratio [HR] 2.31, 95% CI 1.18-4.54, P=.015) and the tumor response to NACT (HR 2.84, 95% CI 1.42-5.67, P=.003) were both significant prognostic factors for PFS. Multivariate analysis also showed that EBV DNA after NACT was the only significant predictor of DMFS (HR 2.99, 95% CI 1.25-7.15, P=.014) and that tumor response to NACT was the only significant predictor of LRFS (HR 3.31, 95% CI 1.21-9.07, P=.020). Detectable EBV DNA levels and an unsatisfactory tumor response (stable disease or disease progression) after NACT serve as predictors of poor prognosis for patients with advanced-stage NPC. These findings will facilitate further risk stratification, early treatment modification, or both before CCRT.

Surgery Alone Versus Surgery Followed by Chemotherapy and Radiotherapy in Resected Extrahepatic Bile Duct Cancer: Treatment Outcome Analysis of 336 Patients.

PurposeThis study analyzed the outcomes of patients with resected extrahepatic bile duct cancer (EHBDC) in order to clarify the role of adjuvant treatments in these patients.Materials and MethodsA total of 336 patients with EHBDC who underwent curative resection between 2001 and 2010 were analyzed retrospectively. The treatment types were as follows: surgery alone (n=168), surgery with chemotherapy (CTx, n=90), surgery with radiotherapy (RT) alone (n=29), and surgery with chemoradiotherapy (CRT, n=49).ResultsThe median follow-up period was 63 months. The 5-year rates of locoregional failure-free survival (LRFFS), distant metastasis-free survival (DMFS), progression-free survival (PFS), and overall survival (OS) for all patients were 56.5%, 59.7%, 36.6%, and 42.0%, respectively. In multivariate analysis, surgery with RT and CRT was a significant prognostic factor for LRFFS, and surgery with CTx was a significant prognostic factor for DMFS, and surgery with CTx, RT, and CRT was a significant prognostic factor for PFS (p < 0.05). Surgery with CTx and CRT showed association with superior OS (p < 0.05), and surgery with RT had marginal significance (p=0.078). In multivariate analysis of the R1 resection patients, surgery with CRT showed significant association with OS (p < 0.05).ConclusionAdjuvant RT and CTx may be helpful in improving clinical outcomes of patients with resected EHBDC who have a high risk of disease recurrence, particularly R1 resection patients. Conduct of additional prospective, larger-scale studies will be required in order to confirm the benefit of adjuvant RT and CTx in these patients.