Mahmoud Abdelsalam

Pre-transplant FDG-PET-based survival model in relapsed and refractory Hodgkin’s lymphoma: outcome after high-dose chemotherapy and auto-SCT

Hodgkin’s lymphoma (HL) patients with positive 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) post salvage chemotherapy or before high-dose chemotherapy and auto-SCT (HDC ASCT) have inferior outcomes. We reviewed 21 prognostic factors before salvage chemotherapy (at relapse/progression) and integrated post salvage FDG-PET results to develop a prognostic model for post HDC ASCT outcome. We used Fine and Gray method for competing risk analysis and regression model for risks assessment and outcome. One hundred and forty-one patients had post salvage FDG-PET before HDC ASCT (median age 25.5 years); male/female 55%:45%, relapsed/refractory 43%:57%, median follow-up 33 months. Multivariate analysis identified HL International Prognostic Score ⩾3 (P=0.001; hazard ratio (HR): 3.7 (1.6–8.3)) and post salvage positive FDG-PET (P=0.011; HR: 3.4 (1.3–8.9)) with higher hazard of disease-specific death (model P=0.0001). Cumulative incidence of disease-specific death with 0, 1, 2 risk factors was 7%:29%:52%, respectively (P=0.00003). For disease-specific event (persistent, progressive or relapsed disease), mediastinal involvement (P=0.024; HR: 2.7 (1.14–6.5)), B symptoms (P=0.027; HR: 2.1 (1.09–4.2)) and positive post salvage FDG-PET (P=0.001; HR: 3.3 (1.7–6.7)) were significant (model P=<0.00001). Cumulative incidence of disease-specific event with 0, 1, 2, 3 risk factors was 8%:31%:50%:75%, respectively (P=0.0000006). Patients with higher scores have higher risk of treatment failure. They are potential candidates for newer therapies along with HDC ASCT.

Primary refractory Hodgkin's lymphoma : outcome after high-dose chemotherapy and autologous SCT and impact of various prognostic factors on overall and event-free survival. A single institution result of 66 patients

We report our experience with high-dose chemotherapy (HDC) and autologous SCT (ASCT) in 66 patients with primary refractory Hodgkins lymphoma (PR-HL) who received salvage chemotherapy followed by BEAM as HDC. Median age at ASCT was 23 years. Before salvage chemotherapy, stages I:II:III:IV were 2:21:14:29, bulky disease 27%, involvement of mediastinum 79%, spleen 26% and extranodal site 47%, 92% had ESHAP as salvage. Post-ASCT evaluation showed response in 50 patients (76%); complete response (CR) 37 (56%), partial response 14 (21%), no response or stable disease 3 (5%) and progressive disease in 10 (15%). Another five patients achieved CR after radiation therapy and one after surgery, making total CR 43 (65%). From diagnosis and HDC, median follow-up is 38.5 and 22.8 months and median overall survival (OS) 78 and 57 months, respectively. Event-free survival (EFS) and OS are 36 and 64%, respectively. In all, 47% patients are in CR. Twenty-two patients (33%) died due to disease. Multivariate analysis showed elevated lactate dehydrogenase (LDH) for EFS (P=0.041) and mediastinal involvement for OS (P=0.038) as negative prognostic factors. In conclusion, EFS and OS are only 36 and 64%, respectively. Elevated LDH and mediastinal involvement are poor prognostic factors.

High-dose chemotherapy and autologous stem cell transplant in adolescent patients with relapsed or refractory Hodgkin's lymphoma

Fifty-eight adolescent patients with relapsed or primary refractory Hodgkins lymphoma underwent high-dose chemotherapy (HDC) and autologous SCT (ASCT). The median age at ASCT was 17 years (range 14–21). The disease had relapsed in 24 patients (41%) and was refractory to initial chemotherapy in 34 (59%). ESHAP salvage chemotherapy before ASCT resulted in 88% response. After ASCT, complete remission (CR; including CR-unconfirmed) was seen in 41 patients (71%) and partial remission in 7 (12%). The overall response rate was 83%. One patient did not respond and nine (15%) had progressive disease. Three more patients achieved CR after consolidative radiation post-ASCT. There was no transplant-related mortality. At a median follow-up of 43 months from ASCT, 31 patients (53%) are alive in CR, 5 (9%) are alive with disease and 22 (38%) have died (21 from disease and 1 unrelated). The actuarial probabilities of event-free and overall (OS) survival are 45 and 55% at 11 years. The only negative prognostic factor for OS was the presence of B symptom at relapse or progression (11-year OS 27 vs 60%, P=0.003).

Co-administration of intravesical bacillus Calmette-Guérin and interferon α-2B as first line in treating superficial transitional cell carcinoma of the urinary bladder.

Study Type – Therapy (individual cohort)

Pre-transplant (18)F-fluorodeoxyglucose positron emission tomography-based survival model in patients with aggressive lymphoma undergoing high-dose chemotherapy and autologous SCT.

18F-fluorodeoxyglucose positron emission tomography (FDG-PET) documented response after salvage chemotherapy has been reported to impact survival in patients with aggressive non-Hodgkin’s lymphoma, especially diffuse large B cell lymphoma (DLBCL) undergoing high dose chemotherapy and autologous SCT (HDC auto-SCT). We reviewed the impact of 19 different prognostic/predictive factors before salvage chemotherapy and post-salvage chemotherapy FDG-PET results in patients with aggressive lymphoma and developed an FDG-PET integrated model for post-HDC auto-SCT outcome. The Fine and Gray method for competing risk analysis and a regression model was used to assess the risk associated with different factors on outcome. Fifty-five patients had FDG-PET after salvage chemotherapy; male 65%, female 45%, relapsed 55%, refractory 45%, DLBCL 82%, T cell lymphoma 18%, median age at auto-SCT 40 years, median follow-up 42.4 months. Multivariate analysis identified only positive FDG-PET (P=0.04) and mediastinal involvement (P=0.05) with higher hazard rate of disease-specific death (model P=0.008) but only positive FDG-PET (P=0.01) for disease-specific events (persistent, progressive or relapsed disease). Cumulative incidence of disease-specific death for patients with 0, 1 and 2 risk factors was 5, 30 and 62%, respectively (P=0.01). Our model is significant and showed an increasing risk of failure with mediastinal involvement and post-salvage positive FDG-PET.

Whole body 18F-FDG PET predicts progression free and overall survival in squamous cell carcinoma of the esophagus: results of a prospective trial

BACKGROUND AND OBJECTIVES 18F-FDG PET yields physiologic information that allows for identifying cancer based on altered tissue metabolism. The aim of this study was to prospectively validate the predictive value of positron emission tomography (PET) in squamous cell carcinoma (SCC) of the esophagus treated by pre-operative chemotherapy followed by esophagectomy. DESIGN AND SETTING Prospective efficacy and toxicity study of patients enrolled between January 1999 and September 2003. PATIENTS AND METHODS Twenty-one patients with SCC of the esophagus who were potentially resectable underwent 18F-FDG PET imaging before the first cycle of neoadjuvant chemotherapy and at least 14 days after the third cycle. A patient was classified as a metabolic responder when the metabolic activity of the primary tumor as measured by the maximum standardized uptake values had decreased by 50% or more at the time of the second 18F-FDG PET. RESULTS The median age of the study cohort was 60 years with a range of 39-70 years; 12 patients were males and 9 were females. 18F-FDG PET had increased activity in the primary tumor in all patients. Metabolic response occurred in 14/21 patients (66%), while 7/21 (33%) patients did not show a metabolic response. Metabolic responders had a high clinical response rate (92%), a median progression free survival (PFS) of 16.4 months and a median overall survival (OS) of 35.3 months. In contrast, prognosis was poor for metabolic non-responders with a clinical response rate of 42% (P=.025), a median PFS of 7.13 months (P=.032) and median OS of 12 months (P=.038). CONCLUSION Our results demonstrate that changes in tumor metabolic activity after neoadjuvant chemotherapy predicts PFS and OS in esophageal SCC patients.

High-dose chemotherapy and autologous stem cell transplantation for Hodgkin's lymphoma in the kingdom of Saudi Arabia: King Faisal specialist hospital and research center experience.

We report our experience with high-dose chemotherapy (HDC) and autologous SCT (ASCT) in 66 patients out of 113 (113 patients out of 153 had complete analysis) with primary refractory Hodgkins lymphoma (PR-HL) who received salvage chemotherapy followed by BEAM as HDC. Median age at ASCT was 23 years. Before salvage chemotherapy, stages I:II:III:IV were 2:21:14:29, bulky disease 27%, involvement of mediastinum 79%, spleen 26% and extranodal site 47%; 92% had ESHAP (etoposide, methylprednisolone, high-dose cytarabine, cisplatin) as salvage. Post-ASCT evaluation showed response in 50 patients (76%), complete response (CR) in 37 (56%), partial response in 14 (21%), no response or stable disease in three (5%) and progressive disease in 10 (15%) patients. Six patients achieved CR after XRT (5) or surgery (1), making a total with CR of 43 (65%). From diagnosis and HDC, median follow-up is 38.5 and 22.8 months and median overall survival 78 and 57 months, respectively. EFS and overall survival (OS) are 36 and 64%, respectively. In all 47% patients are in CR. Twenty-two (33%) patients died of the disease. Multivariate analysis showed elevated lactic dehydrogenase (LDH) for EFS (P=0.041) and mediastinal involvement for OS (P=0.038) as negative prognostic factors. In conclusion, EFS and OS are only 36 and 64%, respectively. Elevated LDH and mediastinal involvement are poor prognostic factors.

Improved survival with combined chemo- radiotherapy in primary central nervous system lymphoma

BACKGROUND Primary CNS lymphoma (PCNSL) is an aggressive primary brain tumor. Cranial irradiation alone rarely results in long-term disease control or prolonged survival. We retrospectively analyzed data on the effect of adding high-dose methotrexate (HDMTX) prior to whole brain irradiation (WBI). METHODS All patients with PCNSL diagnosed and managed during 1991-2004 were identified and demographic characteristics, prognostic factors, treatment and outcome were reviewed. Of 62 patients, 10 were excluded (4 had WBI<40 Gy and 6 had no treatment). Radiation alone was considered curative with a dose>40 Gy. Combined modality therapy included 3-4 cycles of HDMTX (3 g/m2) followed by WBI. RESULT Of 52 patients analyzed for outcome, 36 had WBI (dose>40 Gy), 16 received 3-4 cycles of HDMTX followed by WBI (combined modality therapy [CMT]). Median age was 48.2 years; 42 years in the CMT group, 51 years in WBI. Patient characteristics were comparable between two groups except for higher multifocal tumor in the CMT group (92% vs. x22%, p=.029). Median follow up was 12.83±6.4 months. The hazard ratio for an event was 0.64 (95% CI, 0.52-0.98) and for death 0.58 (95% CI, 0.48-0.92), both in favor of CMT. Univariate regression analysis using one-way analyses of variance (ANOVA) and multivariate Cox regression analysis for prognostic factors including age (<60 vs. >60 years), ECOG PS (0-2 vs. 3-4), extent of surgery (biopsy vs. debulking), solitary vs multifocal tumor and dose of radiation therapy (<50 Gy vs. >50 Gy) failed to identify any prognostic factor. CONCLUSION This retrospective comparison supports phase II trial results that indicate that high-dose methotrexate followed by WBI in PCNSL improves outcome.