Mature Results of a Prospective Trial of Rituximab in Patients (Pt) with Post Transplant Lymphoproliferative Disorder (PTLD) Unresponsive or Ineligible for Reduced Immunosuppression (RIS).

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2755-2755
Author(s):  
Jeff P. Sharman ◽  
Donald E. Tsai ◽  
Clare J. Twist ◽  
Steven M. Horwitz ◽  
Carol D. Jones ◽  
...  

Abstract Background: PTLDs are typically B-cell neoplasms occurring as uncommon but serious complications of reduced T-cell immune surveillance associated with organ transplantation. RIS benefits only a subset of PTLD patients and cytotoxic therapy may be poorly tolerated. Therefore, in October 1998 we initiated a prospective study of rituximab in patients who failed or were unable to receive RIS and now report mature results. Methods: Patients with CD20+ PTLD were eligible if they had failed to completely respond to RIS or RIS was contraindicated and had Karnofsky performance status >60, age 3–70 years (y), measurable disease, and no change in immunosuppression for at least 2 weeks and no cytotoxic therapy within 4 weeks. Rituximab was given as 375 mg/m2 weekly x 4 with disease evaluation at 1, 3, 6, 9, 12 and 18 months. Response data, survival curves, and the impact of clinical and pathological factors were evaluated. Results: 24 of 26 enrolled pt were eligible and evaluable. Median age was 42y with 5 <17 y, 18 were male, and 14 progressed on RIS. Median time to PTLD from transplant was 47 months (m) (8 <24 m). 17/22 were EBV+, 17 were large cell or Burkitt histology, and 10 PTLD occurred in the allograft site. Response rate was 63% (46 %CR, 17% PR) and CRs were durable (1/11 progressed). With median follow-up of 65 m (range 44–82), outcomes at 5 y are: overall survival 48%, freedom from progression 41% and failure-free survival 21%. 7 pt died without progression, yielding 5 y cause-specific survival of 69%. Nine of 13 pt with disease progression were successfully salvaged with second-line therapy. In univariate analysis PTLD characteristics did not significantly correlate with outcome but 2/2 Burkitt pt quickly progressed. Conclusions: Rituximab provided effective, durable treatment for ~40% of pt failing RIS in this series of mainly late PTLD and a majority of pt progressing after rituximab could be treated successfully. However, overall and failure-free survival reflect significant co-morbidity in this population.

2019 ◽  
Author(s):  
Goda Kalinauskaite ◽  
Ingeborg Tinhofer ◽  
Marcus Kufeld ◽  
Anne Kathrin Kluge ◽  
Arne Grün ◽  
...  

Abstract Background: Patients with oligometastatic disease can potentially be cured by using an ablative therapy for all active lesions. Stereotactic body radiotherapy (SBRT) is a non-invasive treatment option that lately proved to be as effective and safe as surgery in treating lung metastases (LM). However, it is not clear which patients benefit most and what are the most suitable fractionation regimes. The aim of this study was to analyze treatment outcomes after single fraction radiosurgery (SFRS) and fractionated SBRT (fSBRT) in patients with lung oligometastases and identify prognostic clinical features for better survival outcomes. Methods: Fifty-two patients with 94 LM treated with SFRS or fSBRT between 2010 and 2016 were analyzed. The characteristics of primary tumor, LM, treatment, toxicity profiles and outcomes were assessed. Kaplan-Meier and Cox regression analyses were used for estimation of local control (LC), overall survival (OS), progression free survival and distant metastases free survival (DMFS). Results: Ninety-four LM in 52 patients were treated using SFRS/fSBRT with a median of 2 lesions per patient (range: 1–5). The median planning target volume (PTV)-encompassing dose for SFRS was 24 Gy (range: 17-26) compared to 45 Gy (range: 20-60) in 2-12 fractions in fSBRT. The median follow-up time was 21 months (range: 3-68). LC rates at 1 and 2 years for SFSR vs. fSBRT were 89% and 83% vs. 75% and 59%, respectively (p=0.026). LM treated with SFSR were significantly smaller (p=0.001). The 1 and 2-year OS rates for all patients were 84% and 71%, respectively. In univariate analysis treatment with SFRS, an interval of ≥ 12 months between diagnosis of LM and treatment, non-colorectal cancer histology and BED <100 Gy were significantly associated with better LC. However, none of these parameters remained significant in the multivariate Cox regression model. OS was significantly better in patients with negative lymph nodes (N0), Karnofsky performance status (KPS) >70% and time to first metastasis ≥12 months. There was no grade 3 acute or late toxicity. Conclusions: We observed good LC and low toxicity rates after SFRS for small lung metastases. Longer time to first metastasis, good KPS and N0 predicted better OS.


2020 ◽  
Author(s):  
Goda Kalinauskaite ◽  
Ingeborg Tinhofer ◽  
Marcus Kufeld ◽  
Anne Kathrin Kluge ◽  
Arne Grün ◽  
...  

Abstract Background: Patients with oligometastatic disease can potentially be cured by using an ablative therapy for all active lesions. Stereotactic body radiotherapy (SBRT) is a non-invasive treatment option that lately proved to be as effective and safe as surgery in treating lung metastases (LM). However, it is not clear which patients benefit most and what are the most suitable fractionation regimes. The aim of this study was to analyze treatment outcomes after single fraction radiosurgery (SFRS) and fractionated SBRT (fSBRT) in patients with lung oligometastases and identify prognostic clinical features for better survival outcomes. Methods: Fifty-two patients with 94 LM treated with SFRS or fSBRT between 2010 and 2016 were analyzed. The characteristics of primary tumor, LM, treatment, toxicity profiles and outcomes were assessed. Kaplan-Meier and Cox regression analyses were used for estimation of local control (LC), overall survival (OS), progression-free survival and distant metastases-free survival (DMFS). Results: Ninety-four LM in 52 patients were treated using SFRS/fSBRT with a median of 2 lesions per patient (range: 1–5). The median planning target volume (PTV)-encompassing dose for SFRS was 24 Gy (range: 17-26) compared to 45 Gy (range: 20-60) in 2-12 fractions in fSBRT. The median follow-up time was 21 months (range: 3-68). LC rates at 1 and 2 years for SFSR vs. fSBRT were 89% and 83% vs. 75% and 59%, respectively (p=0.026). LM treated with SFSR were significantly smaller (p=0.001). The 1 and 2-year OS rates for all patients were 84% and 71%, respectively. In univariate analysis treatment with SFRS, an interval of ≥ 12 months between diagnosis of LM and treatment, non-colorectal cancer histology and BED <100 Gy were significantly associated with better LC. However, none of these parameters remained significant in the multivariate Cox regression model. OS was significantly better in patients with negative lymph nodes (N0), Karnofsky performance status (KPS) >70% and time to first metastasis ≥12 months. There was no grade 3 acute or late toxicity. Conclusions: Longer time to first metastasis, good KPS and N0 predicted better OS. Good LC and low toxicity rates were achieved after short SBRT schedules.


2019 ◽  
Author(s):  
Goda Kalinauskaite ◽  
Ingeborg Tinhofer ◽  
Marcus Kufeld ◽  
Anne Kathrin Kluge ◽  
Arne Grün ◽  
...  

Abstract Background Patients with oligometastatic disease can potentially be cured by using an ablative therapy for all active lesions. Stereotactic body radiotherapy (SBRT) is a non-invasive treatment option that lately proved to be as effective and safe as surgery in treating lung metastases (LM). However, it is not clear which patients benefit most and what are the most suitable fractionation regimes. The aim of this study was to analyze treatment outcomes after single fraction radiosurgery (SFRS) and fractionated SBRT in patients with lung oligometastases and identify prognostic clinical features for better survival outcomes. Methods Fifty-two patients with 94 LM treated with SFRS or fSBRT (Cyberknife, Novalis) between 2010 and 2016 were analyzed. The characteristics of primary tumor, LM, treatment, toxicity profiles and outcomes were assessed. Kaplan-Meier and Cox regression analyses were used for estimation of local control (LC), overall survival (OS), progression free survival and distant metastases free survival (DMFS). Results Ninety-four LM in 52 patients were treated using SFRS/fSBRT with a median of 2 lesions per patient (range: 1–5). The median prescription dose for SFRS was 24 Gy (range: 17-26) compared to 48 Gy (range: 24-75) in 2-12 fractions in fSBRT. The median follow-up time was 21 months (range: 3-68). LC rates at 1 and 2 years for SFSR vs. fSBRT were 89% and 83% vs. 75% and 59%, respectively (p=0.026). LM treated with SFSR were significantly smaller (p=0.001). The 1 and 2-year OS rates for all patients were 84% and 71%, respectively. In univariate analysis treatment with SFRS, an interval of ≥ 12 months between diagnosis of LM and treatment, non-colorectal cancer histology and BED <100 Gy were significantly associated with better LC. However, none of these parameters remained significant in the multivariate Cox regression model. OS was significantly better in patients with negative lymph nodes (N0), Karnofsky performance status (KPS) > 70% and DMFS ≥ 12 months. There was no grade 3 acute or late toxicity. Conclusions We observed good LC and low toxicity rates after SFRS for small lung metastases. Long DMFS, good KPS and N0 predicted longer OS in patients with lung oligometastases.


2021 ◽  
Vol 42 (01) ◽  
pp. 051-060
Author(s):  
Vineet Agrawal ◽  
Smita Kayal ◽  
Prasanth Ganesan ◽  
Biswajit Dubashi

Abstract Background Treatment protocols for acute lymphoblastic leukemia (ALL) have evolved over time to give excellent cure rates in children and moderate outcomes in adults; however, little is known how delays in chemotherapy affect long-term survival. Objectives To find the association of delays during different treatment phases on the survival outcomes. Materials and Methods Data from 149 ALL cases treated between 2009 and 2015 were retrospectively analyzed. Treatment course in commonly used protocols was divided into three phases—induction, consolidation (postremission), maintenance, and also a combined intensive phase (induction plus consolidation) for the purpose of analysis, and delay in each phase was defined based on clinically acceptable breaks. Analysis was done to find the impact of treatment delay in each phase on the survival outcomes. Results The median age was 12 years (range, 1–57). Multi-center Protocol-841 (MCP-841) was used for 72%, German Multicenter Study Group for Adult ALL (GMALL) for 19%, and Berlin, Frankfurt, Muenster, 95 protocol (BFM-95) for 9% of patients. Delay in induction was seen in 52%, consolidation in 66%, and during maintenance in 42% of patients. The median follow-up was 41 months, and 3-year survival outcomes for the entire cohort were event-free survival (EFS)—60%, relapse-free survival (RFS)—72%, and overall survival (OS)—68%. On univariate analysis, delay in induction adversely affected EFS (hazard ratio [HR] = 1.78, p = 0.04), while delay in intensive phase had significantly worse EFS and RFS (HR = 2.41 [p = 0.03] and HR = 2.57 [p = 0.03], respectively). On separate analysis of MCP-841 cohort, delay in intensive phase affected both EFS (HR = 3.85, p = 0.02) and RFS (HR = 3.42, p = 0.04), whereas delay in consolidation significantly affected OS with (HR = 4.74, p = 0.04) independently. Conclusion Treatment delays mostly in intensive phase are associated with worse survival in ALL; attempts should be made to maintain protocol-defined treatment intensity while adequately managing toxicities.


2020 ◽  
Author(s):  
Yuki Mukai ◽  
Yuichiro Hayashi ◽  
Izumi Koike ◽  
Toshiyuki Koizumi ◽  
Madoka Sugiura ◽  
...  

Abstract Background: We compared outcomes and toxicities between concurrent retrograde super-selective intra-arterial chemoradiotherapy (IACRT) and concurrent systemic chemoradiotherapy (SCRT) for gingival carcinoma (GC). Methods: We included 84 consecutive patients who were treated for non-metastatic GC ≥ stage III, from 2006 to 2018, in this retrospective analysis (IACRT group: n=66; SCRT group: n=18).Results: The median follow-up time was 24 (range: 1–124) months. The median prescribed dose was 60 (6–70.2) Gy (IACRT: 60 Gy; SCRT: 69 Gy). There were significant differences between the two groups in terms of 3-year overall survival (OS; IACRT: 78.8%, 95% confidence interval [CI]: 66.0–87.6; SCRT: 50.4%, 95% CI: 27.6–73.0; P = 0.039), progression-free survival (PFS; IACRT: 75.6%, 95% CI: 62.7–85.2; SCRT: 42.0%, 95% CI: 17.7–70.9; P = 0.028) and local control rates (LC; IACRT: 77.2%, 95% CI: 64.2–86.4; SCRT: 42.0%, 95% CI: 17.7–70.9; P = 0.015). In univariate analysis, age ≥ 65 years, decreased performance status (PS) and SCRT were significantly associated with worse outcomes (P < 0.05). In multivariate analysis, age ≥ 65 years, clinical stage IV, and SCRT were significantly correlated with a poor OS rate (P < 0.05). Patients with poorer PS had a significantly worse PFS rate. Regarding acute toxicity, 22 IACRT patients had grade 4 lymphopenia, and osteoradionecrosis was the most common late toxicity in both groups.Conclusions: This is the first report to compare outcomes from IACRT and SCRT among patients with GC. ALL therapy related toxicities were manageable. IACRT is an effective and safe treatment for GC.


Author(s):  
Arvind Sathyamurthy ◽  
Ashish Singh ◽  
Tarun Jose ◽  
Patricia Sebastian ◽  
Rajesh Balakrishnan ◽  
...  

Abstract Aim: To analyse the presentation, diagnosis and patterns of care of extraosseous Ewing sarcoma treated at our institution between 2008 and 2018. Methods: Electronic medical records of extraosseous Ewing sarcoma patients treated at our institution between January 2008 and April 2018 were reviewed. Kaplan–Meier curves were plotted to assess the overall and disease-free survival with 95% confidence intervals. A univariate analysis was carried out to assess the impact of variables such as surgical excision, completeness of surgery, completeness of chemotherapy and addition of radiation therapy on the survivorship. Results: The records of 65 patients treated at our institution were available for review. The mean age was 26·4 years. The most frequent sites of extraosseous Ewing tumour were kidney—9/65 (13·8%) and brain—10/65 (15·4%). Sixteen (24·6%) patients presented with inoperable/metastatic disease at diagnosis. The other 49 (75·4%) had localised disease at presentation. The median overall survival of the 49 non-metastatic patients was 46 months, and the disease-free survival was 45 months. Conclusion: Extraosseous Ewing sarcoma is a rare and aggressive tumour diagnosed by molecular techniques. Multi-modality treatment including surgical resection with wide margins, adjuvant radiation when indicated and completion of systemic chemotherapy results in optimum outcomes.


Author(s):  
Alessandro Moiraghi ◽  
Francesco Prada ◽  
Alberto Delaidelli ◽  
Ramona Guatta ◽  
Adrien May ◽  
...  

Abstract BACKGROUND Maximizing extent of resection (EOR) and reducing residual tumor volume (RTV) while preserving neurological functions is the main goal in the surgical treatment of gliomas. Navigated intraoperative ultrasound (N-ioUS) combining the advantages of ultrasound and conventional neuronavigation (NN) allows for overcoming the limitations of the latter. OBJECTIVE To evaluate the impact of real-time NN combining ioUS and preoperative magnetic resonance imaging (MRI) on maximizing EOR in glioma surgery compared to standard NN. METHODS We retrospectively reviewed a series of 60 cases operated on for supratentorial gliomas: 31 operated under the guidance of N-ioUS and 29 resected with standard NN. Age, location of the tumor, pre- and postoperative Karnofsky Performance Status (KPS), EOR, RTV, and, if any, postoperative complications were evaluated. RESULTS The rate of gross total resection (GTR) in NN group was 44.8% vs 61.2% in N-ioUS group. The rate of RTV > 1 cm3 for glioblastomas was significantly lower for the N-ioUS group (P < .01). In 13/31 (42%), RTV was detected at the end of surgery with N-ioUS. In 8 of 13 cases, (25.8% of the cohort) surgeons continued with the operation until complete resection. Specificity was greater in N-ioUS (42% vs 31%) and negative predictive value (73% vs 54%). At discharge, the difference between pre- and postoperative KPS was significantly higher for the N-ioUS (P < .01). CONCLUSION The use of an N-ioUS-based real-time has been beneficial for resection in noneloquent high-grade glioma in terms of both EOR and neurological outcome, compared to standard NN. N-ioUS has proven usefulness in detecting RTV > 1 cm3.


1991 ◽  
Vol 9 (8) ◽  
pp. 1421-1425 ◽  
Author(s):  
J M Vose ◽  
P J Bierman ◽  
J R Anderson ◽  
D Weisenburger ◽  
D F Moravec ◽  
...  

Patients with Hodgkin's disease who were previously untreated with chemotherapy received the chlorambucil, vinblastine, procarbazine, and prednisone (CHLVPP) regimen plus limited involved-field radiation therapy for treatment of Hodgkin's disease through the Nebraska Lymphoma Study Group. One hundred patients, 87 with newly diagnosed Hodgkin's disease and 13 who relapsed after receiving previous radiation therapy, were treated with this regimen between 1982 and 1989. Complete remissions (CRs) were obtained in 88 of 100 patients (88%), and there have been a total of eight relapses. The overall 3-year failure-free survival was 76%, with good-prognosis patients (ie, Karnofsky performance status greater than or equal to 80) having a 3-year failure-free survival of 87%. Toxicity with this regimen was minimal, with neutropenic fevers reported in 13% of the patient population, moderate alopecia in 5%, and mild to moderate nausea and vomiting in 11% of the patients. As primary induction therapy for Hodgkin's disease, CHLVPP is an effective regimen with a high patient acceptance profile.


BMC Cancer ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Yuki Mukai ◽  
Yuichiro Hayashi ◽  
Izumi Koike ◽  
Toshiyuki Koizumi ◽  
Madoka Sugiura ◽  
...  

Abstract Background We compared outcomes and toxicities between concurrent retrograde super-selective intra-arterial chemoradiotherapy (IACRT) and concurrent systemic chemoradiotherapy (SCRT) for gingival carcinoma (GC). Methods We included 84 consecutive patients who were treated for non-metastatic GC ≥ stage III, from 2006 to 2018, in this retrospective analysis (IACRT group: n = 66; SCRT group: n = 18). Results The median follow-up time was 24 (range: 1–124) months. The median prescribed dose was 60 (6–70.2) Gy (IACRT: 60 Gy; SCRT: 69 Gy). There were significant differences between the two groups in terms of 3-year overall survival (OS; IACRT: 78.8, 95% confidence interval [CI]: 66.0–87.6; SCRT: 50.4, 95% CI: 27.6–73.0; P = 0.039), progression-free survival (PFS; IACRT: 75.6, 95% CI: 62.7–85.2; SCRT: 42.0, 95% CI: 17.7–70.9; P = 0.028) and local control rates (LC; IACRT: 77.2, 95% CI: 64.2–86.4; SCRT: 42.0, 95% CI: 17.7–70.9; P = 0.015). In univariate analysis, age ≥ 65 years, decreased performance status (PS) and SCRT were significantly associated with worse outcomes (P < 0.05). In multivariate analysis, age ≥ 65 years, clinical stage IV, and SCRT were significantly correlated with a poor OS rate (P < 0.05). Patients with poorer PS had a significantly worse PFS rate. Regarding acute toxicity, 22 IACRT patients had grade 4 lymphopenia, and osteoradionecrosis was the most common late toxicity in both groups. Conclusions This is the first report to compare outcomes from IACRT and SCRT among patients with GC. ALL therapy related toxicities were manageable. IACRT is an effective and safe treatment for GC.


2013 ◽  
Vol 23 (9) ◽  
pp. 1590-1596 ◽  
Author(s):  
Pascale Amate ◽  
Cyrille Huchon ◽  
Anne Lucie Dessapt ◽  
Chérazade Bensaid ◽  
Jacques Medioni ◽  
...  

IntroductionImproved knowledge of recurrence sites after contemporary surgical management of ovarian cancer is needed.Material and MethodsWe retrospectively reviewed consecutive patients managed for epithelial ovarian or tubal cancer with surgery and platinum-based chemotherapy between January 1, 2005, and December 31, 2009, in a tertiary teaching hospital. The site of first recurrence was recorded. Univariate analysis was performed to identify factors associated with site-specific recurrence. Overall survival and progression-free survival were computed using the Kaplan-Meier method, and log-rank tests were performed to assess the impact on survival of the variables of interest.ResultsRecurrences were noted in 3 (20%) of 15 International Federation of Gynecologists and Obstetricians stage I to IIa patients and 36 (62.1%) of 58 International Federation of Gynecologists and Obstetricians IIb to IV patients, and the median progression-free survival was 21.6 (2.5–71) and 19.3 (1.8–67.6) months, respectively. In the advanced-disease group, 75% of recurrences involved the peritoneum and 40% were confined to the peritoneum; peritoneal recurrences developed at both treated and untreated sites. Peritoneal recurrence was associated with greater initial peritoneal involvement (Sugarbaker score, 12.1 ± 8.2 vs 7.1 ± 7.4; P = 0.01) and residual postoperative tumor. Nodal recurrences were noted in 38% of all recurrences, usually in combination with peritoneal recurrence and in the abdominal territories. Isolated distant metastasis was a rare mode of recurrence (8%).ConclusionsThe peritoneum is the main recurrence site in both early and advanced ovarian cancer. Initial disease spread and extent of surgery are associated with the recurrence risk. This article supports the view that more attention should be directed toward extensive treatment of the peritoneum.


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