Difference In 5-year Progression-free Survival Research Articles

Dose-Intensification in Early Unfavorable Hodgkin's Lymphoma: Final Analysis of the German Hodgkin Study Group HD14 Trial

In patients with early unfavorable Hodgkin's lymphoma (HL), combined modality treatment with four cycles of ABVD (adriamycin, bleomycin, vinblastine, and dacarbazine) and 30 Gy involved-field radiotherapy (IFRT) results in long-term tumor control of approximately 80%. We aimed to improve these results using more intensive chemotherapy. Patients with newly diagnosed early unfavorable HL were randomly assigned to either four cycles of ABVD or an intensified treatment consisting of two cycles of escalated BEACOPP (bleomycin, etoposide, adriamycin, cyclophosphamide, vincristine, procarbazine, and prednisone) followed by two cycles of ABVD (2 + 2). Chemotherapy was followed by 30 Gy IFRT in both arms. The primary end point was freedom from treatment failure (FFTF); secondary end points included progression-free survival (PFS) and treatment-related toxicity. With a total of 1,528 qualified patients included, the 2 + 2 regimen demonstrated superior FFTF compared with four cycles of ABVD (P < .001; hazard ratio, 0.44; 95% CI, 0.30 to 0.66), with a difference of 7.2% at 5 years (95% CI, 3.8 to 10.5). The difference in 5-year PFS was 6.2% (95% CI, 3.0% to 9.5%). There was more acute toxicity associated with 2 + 2 than with ABVD, but there were no overall differences in treatment-related mortality or secondary malignancies. Intensified chemotherapy with two cycles of BEACOPP escalated followed by two cycles of ABVD followed by IFRT significantly improves tumor control in patients with early unfavorable HL.

Positron emission tomography response at the time of autologous stem cell transplantation predicts outcome of patients with relapsed and/or refractory Hodgkin's lymphoma responding to prior salvage therapy

High-dose chemotherapy followed by autologous stem cell transplantation is the standard treatment for relapsed and/or refractory Hodgkin's lymphoma although half of patients relapse after transplantation. Predictive factors, such as relapse within 12 months, Ann-Arbor stage at relapse, and relapse in previously irradiated fields are classically used to identify patients with poor outcome. Recently, 18-fluorodeoxyglucose positron emission tomography has emerged as a new method for providing information to predict outcome. The aim of this study was to confirm the predictive value of positron emission tomography status after salvage therapy and to compare single versus tandem autologous stem cell transplantation in patients with relapsed and/or refractory Hodgkin's lymphoma. We report a series of 111 consecutive patients with treatment-sensitive relapsed and/or treatment-refractory Hodgkin's lymphoma who achieved complete (positron emission tomography-negative group) or partial remission (positron emission tomography-positive group) at positron emission tomography evaluation after salvage chemotherapy and who underwent single or tandem autologous stem cell transplantation. Five-year overall and progression-free survival rates were 81% and 64%, respectively. There were significant differences in 5-year progression-free survival (79% versus 23%; P<0.001) and 5-year overall survival (90% versus 55%, P=0.001) between the positron emission tomography-negative and -positive groups, respectively. A complete response, as determined by positron emission tomography evaluation, after salvage therapy predicted significantly better 5-year overall survival rates in both intermediate (91% versus 50%; P=0.029) and unfavorable (89% versus 58%; P=0.026) risk subgroup analyses. In the positron emission tomography-positive subgroup, tandem transplantation improved 5-year progression-free survival from 0% (in the single transplantation group) to 43% (P=0.034). Multivariate analysis showed that positron emission tomography status (hazard ratio: 5.26 [2.57-10.73]) and tandem transplantation (hazard ratio: 0.39 [0.19-0.78]) but not risk factors at relapse (hazard ratio: 1.77 [0.80-3.92]) significantly influenced progression-free survival, while only tomography status significantly influenced overall survival (hazard ratio: 4.03 [1.38-11.75]). In patients with relapsed/refractory Hodgkin's lymphoma responding to prior salvage therapy, positron emission tomography response at time of autologous stem cell transplantation favorably influences outcome and enables identification of patients requiring single or tandem transplantation.

Positron Emission Tomography Status and Tandem High-Dose Therapy Favorably Influence Outcome of Patients with Relapsed and/or Refractory Hodgkin Lymphoma

Abstract 335The cure of relapsed or refractory Hodgkin Lymphoma (HL) still remains a challenge. High dose chemotherapy followed by autologous stem cell transplantation (ASCT) is the standard of care but almost half of patients relapse after ASCT and have poor outcome. Predictive factors including an interval from end of first line therapy to relapse shorter than 12 months, an Ann-Arbor stage III or IV at relapse, and relapse in previously irradiated field are currently used to identify patients with poor outcome. Development of 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) assessment improves evaluation of response both in first line and salvage treatments. The aim of our study is first to confirm the predictive value of PET status before ASCT and then to compare ASCT strategy (single versus tandem) in patients with relapsed and/or refractory HL. We here report a series of 111 consecutive patients with relapsed and/or refractory HL who achieved at least partial remission (PR) at PET evaluation after one line of salvage chemotherapy and who underwent single or tandem ASCT. PET response assessment showed 85 (77%) patients in CR (PET- group) and 26 (23%) in PR (PET+ group). Five-year overall (OS) and progression free survival (PFS) were 81% and 64% respectively. There were significant differences in 5-year PFS (79% versus 23%, p<0.001) and 5-year OS (90% versus 55%, p=0.001) between PET- and PET+ groups respectively. This predictive value remained significant in both favorable/intermediate and unfavorable subgroups. In PET+ subgroup analysis, tandem ASCT dramatically improved 5-years PFS, from 0% to 43% (p=0.034) compared to single ASCT. Multivariate analysis showed that PET status (HR: 5.26 [2.57–10.73]) and tandem ASCT (HR: 0.39 [0.19–0.78]) but not relapse risk (HR: 1.77 [0.80–3.92]) significantly influenced PFS, while only PET status significantly influenced OS (HR: 4.03 [1.38–11.75]). Our results suggest that I) PET status before ASCT must be considered as a strong and significant prognostic factor influencing outcome and identifying high risk patients for more intensive strategy II) Tandem ASCT improved outcome compared to single ASCT, especially for PET+ patients. Disclosures:No relevant conflicts of interest to declare.

Endometrial cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up

Endometrial cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up

High-Dose Chemotherapy with Blood or Bone Marrow Transplants for Rhabdomyosarcoma

Rhabdomyosarcoma (RMS), the most common soft-tissue sarcoma in children, is cured with conventional therapy in 70%. However, the 5-year survival for those who relapse is about 30%, and drops to about 15% for those with unfavorable histologies (alveolar/undifferentiated subtypes). We describe outcomes of 62 subjects receiving autologous blood/bone marrow (BM) transplants for RMS between 1989 and 2003, and reported to the Center for International Blood and Marrow Transplantation Research (CIBMTR). Histologic subtype was confirmed by reviewing pathology reports. Treatment-related mortality (TRM), progression-free survival (PFS), and overall survival (OS) were evaluated. Overall, 73% of subjects were <20 years; 39% had cancer bulk >5 cm, 63% had metastasis at diagnosis, 55% had unfavorable histologies, 92% had cancer responsive to chemotherapy pretransplant, and 67% were in first remission. The 1-year TRM was 5% (95% confidence interval [CI], 1%-12%) and the 5-year PFS and OS were 29% (95% CI, 18%-41%) and 32% (95% CI, 21%-44%), respectively. There was only a 4% relapse rate after the first year. There were no differences in 5-year PFS or survival based on histological subtype, transplant in first remission versus relapse (36% versus 29%; P = .5), or transplantation for poor-risk histologies in first remission versus relapse (34% versus 33%; P = .9). Our data indicate that autotransplants for RMS disease are typically done in patients with disease responsive to chemotherapy pretransplant, with approximately one-third long-term survivors. Despite high-risk factors, we also found a low TRM, perhaps reflecting the migration from marrow to blood stem cells as the graft source. Even when performed after relapse for alveolar/undifferentiated histologies, long-term survivals were seen seemingly better than results with conventional therapies.

To Treat Pelvic Nodes or Not: Could the Greater Testicular Scatter Dose From Whole Pelvic Fields Confound Results of Prostate Cancer Trials?

To Treat Pelvic Nodes or Not: Could the Greater Testicular Scatter Dose From Whole Pelvic Fields Confound Results of Prostate Cancer Trials?

External Validation of an International Multicenter Study to Predict Survival in Korean Patients With pT2N0M0 Renal Cell Carcinoma

To determine whether a tumor size cut-off can improve the prognostic accuracy of the current tumor-node-metastasis staging system in Korean patients with pT2 renal cell carcinoma (RCC). We identified 819 patients treated with radical nephrectomy for clinical RCC between 1995 and 2005. The study included 102 patients of pT2N0M0 RCC. When 5-year survival rates were calculated using 0.5-cm increments between 7.5 and 12.5 cm, none of the cut-offs provided a significant difference in 5-year overall and cancer-specific survival. Cut-offs of 9.5 and 10.0 cm provided significant difference in 5-year progression-free survival (log-rank score 4.37, P = .037; log-rank score 6.75, P = .009, respectively). However, a 10.5-cm cut-off provided the greatest difference in 5-year progression-free survival (log-rank score 7.19; P = .007). Multivariate Cox proportional hazards model analysis using the variables of age, sex, American Society of Anesthesiologists score, tumor side, histologic type, tumor grade, and tumor diameters showed that tumor diameter was an independent predictor of progression-free survival when 10.0 cm (hazard ratio [HR], 2.72; 95% confidence interval [CI] 1.19-6.22; P = .018), and 10.5 cm (HR, 2.77; 95% CI 1.21-6.33; P = .016) were chosen as the cut-offs. In our study, only size-related recurrence or metastatic potential was found, and a 10.5-cm cut-off best stratified this difference. However, size-related cancer-specific and overall survival differences were not found among patients.

A randomized phase-III study on adjuvant treatment with radiation (RT) ± chemotherapy (CT) in early-stage high-risk endometrial cancer (NSGO-EC-9501/EORTC 55991)

5503 Background: Adjuvant therapy for early stage high-risk endometrial cancer remains controversial. Methods: Patients with surgical stage I, II, IIIA (positive peritoneal fluid cytology only), or IIIC (positive pelvic lymph nodes only) were eligible if they, according to departmental guidelines, had a sufficiently high risk for micrometastatic disease to qualify for adjuvant therapy. Most patients had two or more of the risk factors: grade 3, deep myometrial invasion, or DNA non-diploidy, while some patients had only one of these. Patients with serous, clear cell, or anaplastic carcinomas were eligible regardless of risk factors. Patients with para-aortic metastases were not eligible. Lymph node exploration at staging surgery was optional. Pelvic RT ± vaginal brachytherapy was given to a dose =44 Gy. CT was given before or after RT. Before August 2004 CT consisted of four courses of cisplatin =50 mg/m2 + doxorubicin 50 mg/m2 or epirubicin 75 mg/m2 (AP). Thereafter several CT regimens were allowed, of which AP, paclitaxel 175 mg/m2 + epirubicin 60 mg/m2 + carboplatin AUC 5, and paclitaxel 175 mg/m2 + carboplatin AUC 5–6 were used. Progression-free survival (PFS) was the primary end-point. The study was terminated before the aimed goal of 400 patients because of slow recruitment. We decided to make an early analysis since new studies on endometrial cancer are presently discussed. Results: 372 patients were entered between May 1996 and Oct 2006. Of 367 evaluable patients 190 were randomized to RT and 177 to RT+CT. Risk factors were well balanced between the randomization arms. The median follow-up time was 3.5 years. The hazard ratio for PFS was 0.58 in favor of RT+CT (95 % confidence interval (CI) 0.34 - 0.99; p=0.046). This translates to an estimated 7 % absolute difference in 5-year PFS from 75 % (95 % CI 67 % - 82 %) to 82 % (95 % CI 73 % - 88 %). Conclusion: RT+CT was better than RT alone. Next question is if RT+CT is better than CT alone. No significant financial relationships to disclose.