Lesion Dissemination in Baseline PET/CT (D-MAX) and IPS Score Predict ABVD Treatment Outcome in PET-2 Negative Advanced-Stage Hodgkin Lymphoma Patients Enrolled in the Prospective GITIL/FIL HD0607 Trial

Abstract Background: Despite its high overall accuracy in predicting ABVD outcome in advanced stage Hodgkin Lymphoma (HL), interim PET performed after 2 chemotherapy cycles (PET-2) showed a sub-optimal negative predictive value (PV) on treatment response. In fact, PET-2 negative patients (p.) treated with six ABVD cycles in four prospective trials (RATHL, GITIL/FIL HD 0607, SWOG 0816 and Echelon-1), showed a 3-Y PFS ranging between 79% to 87%, even declining to 74% after a 5-year follow-up (Stephens 2019). A high Total Metabolic Tumor Volume (TMTV) calculated in baseline PET (cutoff value 471 ml.) , along with a high IPS (≥2) proved able to identify a small p. subset (7%) of PET-2 neg. p. with a 3-Y PFS of only 56% (Gallamini 16° ICML, 2021). A new TMTV-derived parameter aimed to image tumor spread, the tumor distance (DMAX), proved able to predict ABVD outcome in a retrospective series of HL p. from a single center (Durmo, 16° ICML 2021). We report here the PV on ABVD outcome of DMAX combined with IPS in a large cohort of PET-2 negative p. prospectively enrolled in the HD0607 clinical trial. Methods: Out of 783 p. with advanced HL (IIB-IVB) included in the HD0607 clinical trial (NCT00795613), 630 (81%) of them with both negative PET-2 and end-of therapy PET, were randomly assigned to no further therapy or consolidation radiotherapy over the area of a large nodal mass detected at baseline. A single experienced nuclear medicine physician calculated DMAX and TMTV in 331 out of 630 (52%) PET-2 negative p. in which the baseline PET images were available for review. Three different tumor segmentation methods for TMTV computing were chosen, with (1) a relative threshold of 41% of SUVmax in each lesion, (2) a fixed threshold of SUV=2.5 or (3) of SUV=4. DMAX was calculated as the maximum distance among any pixel of the tumor belonging to any lesions in the body. Results: The demographics of the 331 p. included in the present study and of the overall cohort of 630 PET-2 negative p. were: median age 31 (14-60) Vs. 31 (14-60), M/F ratio 0.86 Vs. 0.89; WHO Performance Status 0-1 91.5% Vs. 91.4%; B-symptoms 81.8 Vs. 81.1%; Stage IIB, III and IV 35.0, 35.0, 29.9, Vs.36.3, 33.0 and 30.0%; IPS 0-1 39.3 Vs. 39.8%, IPS 2-3 48.3 Vs. 49.4%, IPS >3 12.4 Vs. 10.6%, Bulky 18.1 Vs. 17.9%. No difference in 6-y PFS was found for p. randomized to NFT or cRT (p=.48; Gallamini JCO 2020). After a median follow-up of 40.6 (4.8-87.2) months, the 3-Y PFS for the 331 p. included in the present analysis and for all the 630 PET-2 negative p. was 84% (95% CI 81% to 87%) and 87% (95% CI, 84% to 89%), respectively. Treatment failure was recorded in 51/331 (15.4%) and 81/627 (12.9%), respectively. Based on a ROC analysis the three different segmentation methods for MTV computing proved to be equivalent (AUC values 0.620-0.525) and hence the 41% threshold was chosen for consistency with previous works. Median and average DMAX values were 12.5 cm. and 15.3 cm. The most accurate cutoff value for DMAX to predict treatment outcome (3-Y PFS) was 16.2 cm., with an AUC of 0.62 (95% CI 0.53-0.70). With this cutoff value DMAX was able to identify two cohorts of patients with a statistically different 3y-PFS: 90% (CI 85-93%) and 76% (95% CI 69-85%), p < 0.001. In multivariate analysis (Cox regression model) including all the above demographics and clinical parameters, as well as TMTV and DMX, only DMAX turned out significant in predicting relapse, with a HR of 1.46 (95% CI1.06-2.01), p=0.02. Upon combining DMAX (higher or lower than 16.2 cm.) and IPS (0-1 Vs. ≥2) in a two-factor predictive model, three categories of p. with a statistically different treatment outcome (P < 0.0001) have been identified: (1) both low DMAX and low IPS, N =30 (9%), 3-Y PFS 100% (95% CI 96-100); (2) either high DMAX and low IPS or high IPS and low DMAX, N= 198 (60%); 3-Y PFS 88% (95% CI 83-93), and (3) both high DMAX and IPS, N= 103 (31%); 3-Y PFS 72% (95% CI 65-82), p<0.0001. Conclusions: DMAX and IPS combined in a predictive model were able to single out three classes of PET-2 negative p. with a statistically different ABVD outcome. P. with a high MTV and a high DMAX, accounting for nearly one-third of p. included in the study, showed the highest risk of failing ABVD, with only 72% of them sustaining a long-term disease control at three years, thus deserving a more aggressive or innovative treatment. The remaining two-thirds had a very good outcome, with a 3-y PFS of 90%, thus stressing that ABVD could remain the standard of care for most PET-2 negative p. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

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Lifetime Weight Characteristics of Adult Inpatients With Severe Anorexia Nervosa: Maximal Lifetime BMI Predicts Treatment Outcome

Frontiers in Psychiatry ◽

10.3389/fpsyt.2021.682952 ◽

2021 ◽

Vol 12 ◽

Author(s):

Lisa-Katrin Kaufmann ◽

Hanspeter Moergeli ◽

Gabriella Franca Milos

Keyword(s):

Anorexia Nervosa ◽

Treatment Outcome ◽

Strong Predictor ◽

Negative Influence ◽

Positive Influence ◽

The Body ◽

Linear Regression Models ◽

Weight Suppression ◽

Positive Treatment

Background: The body mass index is a key predictor of treatment outcome in patients with anorexia nervosa. In adolescents, higher premorbid BMI is a strong predictor of a favorable treatment outcome. It is unclear whether this relationship holds true for adults with anorexia nervosa. Here, we examine adult patients with AN and investigate the lowest and highest lifetime BMI and weight suppression as predisposing factors for treatment outcome.Methods: We included 107 patients aged 17–56 with anorexia nervosa and tracked their BMI from admission to inpatient treatment, through discharge, to follow-up at 1–6 years. Illness history, including lowest and highest lifetime BMI were assessed prior to admission. We used multiple linear regression models with minimal or maximal lifetime BMI or weight suppression at admission as independent variables to predict BMI at admission, discharge and follow-up, while controlling for patients' age, sex, and duration of illness.Results: Low minimal BMI had a negative influence on the weight at admission, which in turn resulted in a lower BMI at discharge. Higher maximal BMI had a substantial positive influence on BMI at discharge and follow-up. Weight suppression was highly correlated with maximal BMI and showed similar effects to maximal BMI.Conclusion: Our findings strongly support a relationship between low minimal lifetime BMI and lower BMI at admission, and between higher maximal lifetime BMI or weight suppression and a positive treatment outcome, even years after discharge. Overall, maximal BMI emerged as the most important factor in predicting the weight course in adults with AN.

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Prognostic Factors and Treatment Outcome in Lymphocyte Predominant and Classical Hodgkin’s Lymphoma: A Comprehensive Analysis of the German Hodgkin Study Group.

Blood ◽

10.1182/blood.v108.11.97.97 ◽

2006 ◽

Vol 108 (11) ◽

pp. 97-97

Author(s):

Lucia Nogova ◽

Thorsten Reineke ◽

Corinne Brillant ◽

Thomas Ruediger ◽

Hans K. Mueller-Hermelink ◽

...

Keyword(s):

Treatment Outcome ◽

Prognostic Factors ◽

Hodgkin Lymphoma ◽

Cox Regression ◽

White Cell Count ◽

Advanced Stage ◽

Treatment Protocols ◽

Cox Regression Analysis ◽

Negative Factor ◽

Advanced Stages

Abstract Introduction: Lymphocyte predominant Hodgkin lymphoma (LPHL) differs in histological and clinical presentation from classical Hodgkin lymphoma (cHL). Treatment of LPHL patients using standard approaches leads to complete remission (CR) in more than 95% of patients. However, differences in terms of relapse rates, overall survival (OS) and freedom from treatment failure (FFTF) between LPHL and cHL patients were suggested by a recent intergroup analysis. To obtain a more comprehensive picture, we reviewed all LPHL-cases registered in the GHSG database comparing patient characteristics and treatment outcome with cHL patients. Patients and methods: We retrospectively analyzed 8298 HL patients treated within the GHSG trials (HD4 to HD12). 394 patients had LPHL and 7904 cHL. From 394 LPHL patients, 63% were in early favorable stage, 16% in early unfavorable and 21% in advanced stage of disease. Of the 7904 cHL patients analyzed, 22% were in early favorable, 39% in early unfavorable and 39% in advanced stages. 9% of LPHL patients had B symptoms compared to 40% in cHL patients. Results: 91% LPHL vs. 86% cHL patients in early favorable stages, 86% vs. 83% in early unfavorable and 79% vs. 75% in advanced stages reached CR/CRu. 0.3% LPHL patients developed progressive disease (PD) compared to 3.7% cHL patients. The relapse rate of LPHL patients was very similar to cHL (8.1% vs. 7.9%). There were 2.5% secondary malignancies in LPHL and 3.7% in cHL patients. 4.3% LPHL patients and 8.8% cHL patients died. The FFTF rates for LPHL and cHL patients at a median observation of 41 or 48 months were 88% and 82% (p=0.0093), respectively. The OS for LPHL and cHL patients was 96% and 92%, respectively (p=0.0166). The analysis between LPHL stages showed significant differences in FFTF (p=0.0239). According to a multiple Cox-regression analysis, advanced stage (p=0.0089) and lymphocytes < 8% of white cell count was shown as negative prognostic factors for FFTF and age ≥ 45 years (p=0.008) as negative factor for OS in LPHL patients. Hb value < 10.5 g/dl was shown as negative factor for both, FFTF and OS (p=0.0125, p=0.0002). Conclusion: This is the largest analysis comparing LPHL and cHL patients. We found differences in FFTF and OS rates between both groups and differences in FFTF between LPHL stages. New treatment protocols for LPHL patients with reduced intensity schedules are to be discussed.

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FDG-PET Guided Consolidative Radiotherapy in Patients with Advanced Stage Hodgkin Lymphoma with Residual Abnormalities on Post Chemotherapy CT Scan.

Blood ◽

10.1182/blood.v110.11.213.213 ◽

2007 ◽

Vol 110 (11) ◽

pp. 213-213 ◽

Cited By ~ 1

Author(s):

Kerry J. Savage ◽

Joseph M. Connors ◽

Don Wilson ◽

Richard Klasa ◽

Tamara Shenkier ◽

...

Keyword(s):

Hodgkin Lymphoma ◽

Fdg Pet ◽

Ct Imaging ◽

Pet Scan ◽

Stage Iii ◽

Advanced Stage ◽

Bulky Disease ◽

Residual Mass ◽

Consolidative Radiotherapy

Abstract Consolidative radiotherapy (RT) is often administered following chemotherapy for advanced stage Hodgkin lymphoma (HL) with bulky disease at diagnosis or for residual abnormalities on post-chemotherapy CT imaging. It is unknown whether RT is necessary for such patients if the residual mass is FDG-PET-negative (PET-neg) following chemotherapy (CHT). Further, it has been previously shown that a post-therapy PET-positive (PET-pos) scan is highly predictive of future relapse; however, it is unclear whether consolidative RT can be used to salvage these cases. Methods Since July 2005, adult (> 16 y) patients in British Columbia (BC) with advanced stage HL (stage III /IV and/or the presence B symptoms and/or bulky disease (> 10cm)) have been treated with 6 cycles with ABVD followed by a PET scan for further treatment planning if residual abnormalities ≥2 cm were observed on CT imaging. Prior to this, post-treatment PET scans were obtained in some individuals by self-pay. If the PET scan was positive, RT was administered if feasible, otherwise, patients were observed. There were 68 eligible patients, including 7 self-pay patients, that were identified in the BC Lymphoid Cancer Database. 16 patients were excluded (PET not performed (5); palliative tx or refusal (3); composite lymphoma (1); progressive disease during CHT or at the time of PET scan (4); HIV + (1); PET mid-therapy (1); death due to unrelated cause prior to PET scan (n=1).), leaving a total of 52 patients who had a PET scan post-chemotherapy for a residual mass and who had adequate follow-up (median 19 m, 10–59 m). Patient characteristics include: M:F 1.1:1, Median age 29 (17–81); 55% stage II, 46% stage III/IV 44%; 49% bulky disease; 69% B symptoms; IPFP Prognostic score 0 8%; 1 39%; 2 26%; >3 26%. Results In total, 40/52 (77%) were PET-neg and 12/52 (23%) were PET-pos (SUV mean 4.4, 2.2–6.8). PET-pos patients had an inferior 2 y PFS compared to PET-neg patients (26% vs 91%, p=.001). In the PET-pos group, 10/12 received the planned RT and 5 have relapsed. In the PET-neg group, there was no difference in the 2 y PFS in patients with bulky (n=17) vs non-bulky disease (n=20) (86% vs 94%, p=.35). Conclusions Advanced stage HL patients who achieve a post-CHT PET-neg status are at a low risk of relapse and do not require additional consolidative RT thus avoiding potential long-term side effects. The majority of patients with bulky disease who have a PET-neg scan following CHT also remain in remission, however, longer follow-up is still needed. Although some patients with a positive PET-scan may be salvaged by consolidative RT, a high proportion ultimately relapse. Figure Figure Figure Figure

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FDG-PET for Assessment of Residual Tissue after Completion of Chemotherapy in Hodgkin Lymphoma - Report on the 2nd Interim Analysis of the PET Investigation in the Trial HD15 of the GHSG.

Blood ◽

10.1182/blood.v110.11.212.212 ◽

2007 ◽

Vol 110 (11) ◽

pp. 212-212 ◽

Cited By ~ 1

Author(s):

Volker Diehl ◽

Carsten Kobe ◽

Heinz Haverkamp ◽

Markus Dietlein ◽

Andreas Engert

Keyword(s):

Hodgkin Lymphoma ◽

Progression Free Survival ◽

Multicenter Trial ◽

Study Endpoint ◽

Tumour Mass ◽

Residual Tumour ◽

Advanced Stage ◽

Skeletal Involvement ◽

Significant Difference

Abstract Introduction The prospectively randomized HD15 multicenter trial of the German Hodgkin Study Group (GHSG) included advanced-stage Hodgkin lymphoma patients comparing 8 cycles of BEACOPPescalated with 6 cycles or 8 cycles time-condensed BEACOPPbaseline. One other main study endpoint was the prognostic value of 18F-fluorodesoxyglucose (FDG) positron emission tomography (PET) following chemotherapy. The aim was to specify the negative predictive value of PET (NPV) in patients with residual tumour mass after chemotherapy. Methods Entry criteria for the PET question were partial remission (PR) after the end of chemotherapy with at least one involved nodal site measuring more than 2.5 cm in diameter by computed tomography (CT). Exclusion criteria included diabetes, elevated blood sugar levels and skeletal involvement with risk of instability. Calculations were restricted to those cases with either progressive disease (PD) or relapse within 12 months after PET or at least 12 months of follow-up. A total of 275 patients were eligible for this analysis. The assessment was based on those patients confirmed by an expert panel as being PET-negative. CT verification was performed to identify false positive PET findings. The NPV was defined as the proportion of patients without progression or relapse within 12 months. Results 9/216 patients with PET-negative residues and 9/59 patients with PET-positive residues had PD or relapse within one year of follow-up. The NPV was 0.958% (95% CI 0.931 – 0.985%). In 244/245 cases with PET-negative residual masses, no irradiation was given. In the 62/66 cases with PET-positive residues, additional radiotherapy was performed. Progression/relapse rates were significantly different between those patients with residual mass being PET-negative or PET-positive (p=0.0053). PET-negative patients, who were assessed as partial response by CT, had a prognosis similar to those in complete remission. There was no significant difference in the progression free survival in this trial and the prior GHSG trials HD12 (arms pooled) and HD9 (arm C) for advanced-stage HL (p=0.266). Importantly, the proportion of patients receiving radiotherapy decreased from 70% (HD9-C) to 39% (HD12) and 12% (HD15). Discussion The high NPV of PET suggests that radiotherapy following 6 or 8 cycles of BEACOPP might be restricted to those patients who are PET-positive after chemotherapy.

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Long-Term Follow-Up of BEACOPPescalated Chemotherapy in Patients with Advanced-Stage Hodgkin Lymphoma on Behalf of the German Hodgkin Study Group.

Blood ◽

10.1182/blood.v110.11.211.211 ◽

2007 ◽

Vol 110 (11) ◽

pp. 211-211

Author(s):

Engert Andreas ◽

Jeremy Franklin ◽

Volker Diehl

Keyword(s):

Hodgkin Lymphoma ◽

Secondary Malignancy ◽

Tumor Control ◽

Study Group ◽

Advanced Stage ◽

Secondary Aml ◽

German Hodgkin Study Group ◽

Long Term Follow Up

Abstract The HD9 trial of the German Hodgkin Study Group (GHSG) compared two different doses (baseline and escalated) of the novel chemotherapy regimen BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone) in patients with advanced-stage Hodgkin lymphoma (HL). The previous analysis with a median follow-up of 5 years showed improved tumor control (FFTF) and overall survival (OS) for BEACOPPescalated. Since BEACOPPescalated had been associated with more toxicity as compared with ABVD we report the results of long-term follow-up of 1196 patients enrolled and randomized in that study. The median follow-up was 112 months; a total of 370 centres contributed. Patients received one of three chemotherapy regimens: 8 cycles of COPP (cyclophosphamide, vincristine, procarbazine, and prednisone) alternating with ABVD (doxorubicin, bleomycin, vinblastin, and dacarbazine), 8 cycles of standard-dose BEACOPP or 8 cycles of escalated-dose BEACOPP. At 10 years, FFTF rates were 64%, 70% and 82%, OS rates were 75%, 80%, and 86 for COPP-ABVD (arm A), BEACOPPbaseline (arm B), and BEACOPPescalated, respectively (p < 0,001). Importantly, BEACOPPescalated was also significantly better than BEACOPPbaseline in terms of FFTF (p < 0.0001) and OS (p = 0.0053). Death due to HL occurred in 11.5%, 8.1% and 2.8% in arms A, B, and C, respectively. 74 second malignancies were documented, including secondary acute myeloid leukaemias (1,7,14), Non-Hodgkin lymphoma (7,8,5), and solid tumors (7,16,9) in arms A, B, and C respectively. The corresponding overall secondary malignancy rates were 6.7%, 8.9% and 6.8%. Importantly, the risk of secondary AML (sAML), although increased in this study after BEACOPPescalated, amounts to 0.9% in our follow-up study with BEACOPPescalated (HD12) in 1502 advanced-stage HL patients randomized and four years median follow-up. Although the higher rate of secondary AML after BEACOPPescalated in HD9 most likely occurred by chance, interestingly, 70% of patients in this group had additional radiotherapy whereas only 39% were radiated in HD12. Taken together, the 10 years follow-up of BEACOPPescalated chemotherapy demonstrates a stabilized significant improvement in long-term FFTF and OS for advanced-stage HL. Although for formal prove the results of ongoing prospective randomized comparisons with 8 cycles of ABVD might be required, these results clearly challenge ABVD as standard of care for this patient population.

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PET-CT Adapted Therapy After 3 Cycles of ABVD for All Stages of Hodgkin Lymphoma. Interim Analysis in 173 Patients

Blood ◽

10.1182/blood.v116.21.1772.1772 ◽

2010 ◽

Vol 116 (21) ◽

pp. 1772-1772

Author(s):

Santiago Pavlovsky ◽

Astrid Pavlovsky ◽

Isolda Fernandez ◽

Miguel Pavlovsky ◽

Virginia Prates ◽

...

Keyword(s):

Overall Survival ◽

Hodgkin Lymphoma ◽

Progressive Disease ◽

Cell Transplant ◽

Advanced Stage ◽

Event Free Survival ◽

Bulky Disease ◽

Free Survival ◽

Pet Ct

Abstract Abstract 1772 Background: Hodgkin Lymphoma (HL) is the most curable type of Lymphoma with an overall survival at 5 years of 80%. ABVD can be considered as gold standard for first line treatment for all stages of HL. Dividing patients (pts.) in different prognostic groups has aimed to reduce chemo and radio toxicity in those patients with good prognosis. A negative PET-CT, either early during treatment of ABVD or after completion of it, has shown to be a powerful prognostic tool (Hutchings: Blood 2006; Gallamini: Haematologica 2006). Our cooperative group has an experience with 584 patients with HL in early or advanced stage treated with 3 or 6 cycles of ABVD plus involved field radiotherapy with a complete remission (CR) of 91% and an event free survival (EFS) and overall survival (OS) at 60 months of 79% and 95%.(S Pavlovsky, Clin Lymp My & Leuk, 2010). Aims: Test the efficacy of treatment to all stages of HL adjusted to PET-CT results after 3 cycles of ABVD. Evaluate the outcome of pts. who have a negative PET-CT after 3 cycles of ABVD and receive no further treatment. Intensify therapy only in pts. who have persistent hyper metabolic lesions in PET-CT after 3 cycles of ABVD. Method: Since October 2005, 198 newly diagnosed pts. with HL have been included in a prospective multicenter trial. Initially all patients received 3 cycles of ABVD. After the third cycle, pts. were evaluated with a PET-CT. Those pts. who achieved CR with a negative PET-CT, received no further treatment. Those with more than 50% of anatomic reduction of initial masses but persistent hyper metabolic lesions by PET-TC after 3 ABVD were considered in partial remission (PR) and completed 6 cycles of ABVD and radiotherapy (RT) on PET-CT positive areas. Those patients with less than PR after 3 cycles of ABVD received ESHAP and if CR, high doses of chemotherapy and an autologous stem cell transplant (ASCT). All patients were re-evaluated at the end of treatment. The median follow up is of 30 months (3-62). Results: One hundred and seventy three patients completed three cycles of ABVD followed by a PET-CT. The median age at diagnosis was 29 years. One hundred and thirty-six (79%) had localized stage (I-II) at diagnosis and 37 (21%) presented with advanced stage (III-IV). Of 155 pts. 77 (50%) pts had IPS 0–1, 66 (43%) had IPS 2–3 and 12 (8%) had IPS 4–5. Twenty six (17%) pts. had bulky disease at diagnosis. One hundred and thirty-seven (79%) pts. achieved CR with negative PET-CT after 3 cycles of ABVD. Thirty-six (21%) were PET-CT positive, of them 32 pts achieved PR and completed a total of 6 cycles of ABVD plus RT in hyper metabolic lesions. Twenty five achieved CR (72%), 5 persisted with PR and 2 died of progressive disease. Four pts showed progressive disease (PD) after 3 ABVD and received ESHAP and ASCT, 2 achieved and remained in CR, 1 is in PR and 1 died of progressive disease. Of 173 pts who completed treatment with ABVD × 3 cycles, ABVD × 6 cycles plus RT on PET-TC positive areas or ESHAP plus ASCT, 164 pts (95%) achieved CR. Of these 164 pts., 14 pts (8%) relapsed. The EFS and OS at 36 months is 83% and 97% respectively. Patients with early negative PET-TC have an event-free survival of 87% compared to 62% (P=0,001) for pts with early positive PET CT. The OS at 36 months was 100% versus 86% respectively (<0.001). Conclusion: Treating patients with ABVD, evaluating response after 3 cycles with PET-CT, and adapting further therapy, leads to a high rate of CR avoiding more aggressive chemotherapy and radiotherapy. Three courses of ABVD without RT are adequate in patients with early CR defined by negative PET-CT. In early positive PET-CT it is possible to intensify therapy improving the otherwise bad prognosis; more aggressive treatment might also be suitable. These results need to be confirmed by a larger group of patients and a longer follow-up. Disclosures: No relevant conflicts of interest to declare.

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Primary Pancreatic Lymphoma

Blood ◽

10.1182/blood.v116.21.4150.4150 ◽

2010 ◽

Vol 116 (21) ◽

pp. 4150-4150 ◽

Cited By ~ 1

Author(s):

Elisabeth S. Malin ◽

Christiana E. Toomey ◽

Jill Ono ◽

Aliyah R. Sohani ◽

James S. Michaelson ◽

...

Keyword(s):

Board Of Directors ◽

Hodgkin Lymphoma ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

The Body ◽

Advisory Committees ◽

Not Otherwise Specified ◽

Hodgkin's Lymphomas ◽

Pancreatic Lymphoma

Abstract Abstract 4150 Introduction: Primary extranodal pancreatic non-Hodgkin lymphoma (PPL) makes up no more than 0.16–4.9% of pancreatic malignancies and less than 0.7% of non-Hodgkin's lymphomas (NHL). Since lymphomas involving the pancreas may have a similar clinical presentation to primary pancreatic adenocarcinoma, and often have a similar radiographic appearance, pancreatic lymphoma is often not diagnosed until surgical exploration or definitive surgery for presumed pancreatic cancer. Preoperative distinction of adenocarcinoma and PPL is critical as the management and prognoses of these malignancies are mutually exclusive. The rarity of PPL has made epidemiologic studies difficult to conduct. Methods: We queried our IRB-approved clinicopathologic database, derived from comprehensive tumor registry data at the Massachusetts General Hospital, for all adult patients diagnosed with PPL between 2000 and 2010. The database contains 5821 patients with mature lymphoid malignancies. Cases were included in the analysis if they met clinicopathologic criteria for PPL, defined as dominant disease presentation within the body of the pancreas. Forty-five patients were found to have pancreatic involvement at initial presentation of whom 31 (68.9%) on further investigation had a pancreatic primary and are included in the analysis. For each patient, we collected complete demographic information, clinical presenting features, histology, chemotherapy regimens, use of radiotherapy, and type of surgical biopsy performed. We also collected outcome data including results of interim and final restaging scans. Results: PPL represented 0.5% of all mature lymphomas seen at our institution. The median age at diagnosis was 60 yrs (range 20–91). There were 21 male and 10 female patients. Eighteen patients had Diffuse Large B Cell Lymphoma (DLBCL) (one with a focus of follicular lymphoma (FL) grade 3), two each had Burkitts Lymphoma, FL Grade 1–2, and mantle cell lymphoma (MCL), and one each had small lymphocytic lymphoma (SLL), Hodgkin Lymphoma, Marginal zone lymphoma, and peripheral T cell Lymphoma not otherwise specified. Three patients had NHL not otherwise specified (NOS). Of the 31 patients, 13 patients were stage 4E, 5 were stage 3E, 8 were stage 2E, and 5 were Stage 1E. Seventeen patients presented with jaundice. In 2 cases clinical history at presentation was unavailable. Elevated lactate dehydrogenase (LDH) level was present in 18 of 26 patients (69%) for whom laboratory values were available. B symptoms were present at diagnosis in 13 patients, absent in 17 patients, and unavailable in 1. Diagnosis was made in sixteen patients by fine needle aspiration (FNA), in nine patients by core needle biopsy, in two by incisional biopsies, and four patients were diagnosed after a definitive pancreaticoduodenectomy (Whipple procedure). Information on therapeutic regimen was available for 24 patients. One of these 24 patients was treated with primary radiotherapy without chemotherapy for a grade 1–2 primary pancreatic FL. Twenty-three patients had initial chemotherapy: 8 with R-CHOP, 5 with CHOP, 2 with CVP, and 1 each with CHOP-14, CVP × 1 then CHOP, R-CVP, R-EPOCH, R-CODOX-M/R-IVAC, R-CDOP and R-CP then R-CHOP. One patient was treated with chemotherapy not otherwise specified in the medical record. Four of these 23 patients received consolidative radiotherapy after initial therapy. Chemotherapy had significant efficacy with an overall response rate (ORR) of 75% in all chemotherapy treated patients (10 CR, 8 PR). Therapy information was available on 13 patients with DLBCL with an ORR of 85% (7 CR, 4 PR) to R-CHOP in 8 patients, CHOP in 3, and 1 each R-EPOCH and R-CDOP. One patient died of meningeal relapse of DLBCL despite therapy with R-EPOCH. For the entire PPL group at median follow-up of 28.5 months, the progression free and overall survivals are 48.4% and 64.5%, respectively. At a median follow-up of 33.4 months, the progression free and overall survivals for the DLBCL-PPL group are 50.0% and 66.7%, respectively. Discussion: PPL is a rare extranodal presentation of lymphoma accounting for 0.5% of lymphomas seen at a tertiary referral center. Pre-surgical diagnosis of PPL is critical to avoidance of unnecessary major surgery. The outcome of PPL approximates the outcome of DLBCL in other sites. An increased rate of CNS relapse was not seen with presentations in this extranodal site. Disclosures: Hochberg: Biogen Idec: Speakers Bureau; Genentech: Speakers Bureau; Enzon Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen: Speakers Bureau; WorldCare: Membership on an entity's Board of Directors or advisory committees; Proventys: Consultancy.

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Interim-PET Scan Interpretation In the Ongoing Prospective Clinical Trial HD 0607, In Advanced-Stage Hodgkin Lymphoma: Results of the the Expert Panel Review

Blood ◽

10.1182/blood.v116.21.3891.3891 ◽

2010 ◽

Vol 116 (21) ◽

pp. 3891-3891

Author(s):

Andrea Gallamini ◽

Alberto Biggi ◽

Stephane Chauvie ◽

Alexandru Stancu ◽

Federico Fallanca ◽

...

Keyword(s):

Clinical Trial ◽

Hodgkin Lymphoma ◽

Expert Panel ◽

Concordance Rate ◽

Advanced Stage ◽

Perfect Agreement ◽

Fdg Uptake ◽

Interim Pet ◽

Deauville Score ◽

Negative Scan

Abstract Abstract 3891 Background: several PET response-adapted prospective clinical trials are running at the moment, aimed at assessing the role of chemotherapy intensification in ABVD-treated Hodgkin Lymphoma (HL) patients with interim PET-positive after 2 cycles (PET-2). Standard interim-PET interpretation rules are still lacking, and expert review panels for PET interpretation have been implemented in these trials. We report here the results of PET-2 review in the HD 0607 trial. Patients and methods: starting from July 2008 till now, 236 advanced-stage HL patients have been consecutively enrolled in the Italian GITIL (Gruppo Italiano Terapie Innovative nei Linfomi) prospective multicenter clinical trial HD 0607 (NCT Identifier: NCT00795613). Advanced-stage (IIB-IVB) HL patients are first treated with 2 ABVD courses and PET-2 performed afterwards. All the non-negative PET-2 scan are reviewed by the expert panel. Non-negative PET-2 is defined as any scan with any residual FDG uptake outside the physiological areas of the tracer concentration. All the non-negative PET-2 according to the local centers (PET-2loc) are uploaded on the dedicated website (http://magic5.to.infn.it/gitil), along with the baseline scans. Six independent reviewers re-interpret the scans according to the 5-point semiquantitative score with mediastinum and liver as reference organs for residual fluorodeoxyglucose (FDG) uptake (Deauville score, Meignan 2009). The first three reviewers replying within 72 hours from PET upload determine the panel final decision; the remaining three report the scans later. Patients with a score 4 or 5 shifted to BEACOPP or Rituximab-BEACOPP escalated treatment; patients with score 1–3 continued with ABVD. Patient with bulky lesion (defined as a nodal mass with the largest diameter 3 6 cm) were treated with IF-RT. Results: 199/236 patients performed a PET-2 scan: 131 (66%) showed a negative, 68 (33%) a non-negative scan. These 68 PET-2loc were reviewed (PET-2rev.); the clinical characteristics of patients with a reviewed and unreviewed PET-2loc were the following: mean age 32 vs.35, Stage III 19/68 (28%) and 61/131(46%), Stage IV 26/68 (39%) and 45/131 (34%), Bulky 44/68 (65%) and 93/131 (71%), IPS 3 or more 20/68 (29%) and 20/131 (15%), respectively. As a result of review there were 32 positive PET-2rev. and 36 negative PET-2rev. The median PET-2 review time from the uploading in the website to the third reviewer's report was 48 hours (1-90). The 32 positive PET-2rev scans showed a single residual focus in 28 and multiple foci of residual FDG uptake in 4 cases (all score 5). 22 showed a single lesion in the mediastinum, 4 in superficial lymph nodes and 2 in the lung. In 25/28 (89%) patients the single residual FDG uptake was within a bulky lesion and in 3/28 was outside it. The concordance rate among couples of reviewers for a positive vs. negative scan, measured with Cohen's Kappa, ranged between 0.76 (substantial agreement) and 0.92 (almost perfect agreement). The overall concordance rate measured with Krippendorf's Alpha, (assuming chance = 0 and perfect agreement =1) was 0.82. Lower concordance among reviewers was found in scans showing FDG residual uptake in anatomical structures not clearly related to lymphoma (brown fat, large vessels, bowel, tonsil, and inflammatory lung lesions). Conclusions: these data show that (1) the preliminary reports of a very high binary and overall concordance rate among reviewers using the Deauville score for PET-2 reporting (Barrington 2010) have been confirmed; (2) the online review process for PET-2 scan is feasible and simple; (3) most of the positive PET-2 scan showed a residual FDG uptake in the site of bulky disease, mostly in mediastinum. Disclosures: No relevant conflicts of interest to declare.

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Cost-Effectiveness of Interim PET Response Adapted Therapy In ABVD-Treated, Advanced-Stage Hodgkin Lymphoma

Blood ◽

10.1182/blood.v118.21.1563.1563 ◽

2011 ◽

Vol 118 (21) ◽

pp. 1563-1563 ◽

Cited By ~ 1

Author(s):

Andrea Gallamini ◽

Monia Marchetti ◽

Anna Borra ◽

Roberto Sorasio ◽

Francesca Fiore

Keyword(s):

Quality Of Life ◽

Health Care ◽

Sensitivity Analysis ◽

Cost Saving ◽

Disease Control ◽

Hodgkin Lymphoma ◽

Advanced Stage ◽

Interim Pet

Abstract Abstract 1563 Background: ABVD chemotherapy (AT) is the standard treatment for patients with advanced-stage Hodgkin lymphoma (HL). However, BEACOPP achieves a higher disease control at a cost of a definitely higher toxicity. Positron emission tomography (PET) after two chemotherapy cycles (PET2) is the most reliable predictor of treatment outcome in ABVD-treated patients. A PET-2 response-adapted strategy with a therapy shift from ABVD to BEACOPP in PET2 positive patients (A/B-T) was shown to increase the 2-y Failure Free Survival (FFS) in the latter from 12% to 62% by indirect retrospective comparison, and to improve the disease control in the overall patient population (Gallamini Br. J. Haematol 2011). However, PET is an expensive test which deserves a careful economic assessment before widespread adoption and reimbursement. Methods: We built a Markov decision model comparing A/B-T with AT strategies for advanced HL. The model was calibrated on the reported retrospective cohort of 154 ABVD-treated HL patients in which treatment intensification with BEACOPP was given in PET-2 positive patients. Briefly, patients were treated with standard ABVD × 2 courses and an interim-PET performed afterwards: PET-2 negative patients continued with ABVD × 4 and consolidation RxT in presence of bulky disease; PET-2 positive patients shifted to BEACOPP escalated × 4 + BEACOPP baseline × 4. Patients failing either AT or A/B-T underwent rescue treatment with IGEV × 4, followed by Autologous Stem Cell Transplantation (ASCT). In patients failing ASCT, DHAP reinduction therapy was given and allogeneic SCT (alloSCT) was performed whenever possible. The model included 12 health-states: ABVD cycles 1–2, ABVD cycles 3–6, BEACOPP escalated (4 cycles), BEACOPP baseline (4 cycles), IGEV (4 cycles), ASCT, DHAP + allogeneic SCT, follow-up (FFS patients PET2 negative), follow-up (FFS patients PET2 positive), follow-up (FFS after ASCT/CST), relapse, death. Each health state last 1 month and the overall time horizon at baseline was 5 years. We considered severe toxicity needing inpatient care and transplant-related mortality. Quality of life was reduced by 20% for chemotherapy-treated patients, 30% for transplanted ones and 40% in relapsed ones. The model assessed the following endpoints: survival, quality of life – adjusted survival (QALY) and costs (in the perspective of the health-care system) as the principal end-points. TreeAge SW (2008) was run. National charges were used as estimators of unitary costs. First and second-order sensitivity analysis was performed. Results: A/B-T reduced the overall percentage of patients failing treatment (refractory and relapsing) from 27% to 14%. This clinical advantage induced a prolongation of quality-adjusted survival from 53.20 to 55.63 quality-adjusted months, that is a gain of 0.18 QALYs (90% CI: −0.1;+1.4). The number of interim PET needed to avoid one ASCT was 8.3. The cost of universal interim PET (€1,546) was offset by the reduced number of ASCT procedures (€36,575). Consequently, health-care costs were €27,861 for A/BT versus €29,050 for AT strategy which is a €1189 (90%CI: −41,208; +13,240) saving. At sensitivity analysis we verified that the results were mildly sensitive to the costs of PET and ASCT: A/B-T was not cost saving if PET would cost more than €3,031 and ASCT less than €20,200. A/B-T would cost more than €40,000/QALY only at a PET cost higher than €16,300. The results were also sensitive to the portion of PET2 positive patients: A/B-T wouldn't turn out cost saving if the portion was higher than 22%. The results were not sensitive to the rate of severe adverse events during chemotherapy. The results were overall robust, since A/B-T cost less than €30,000/QALY in more than 80% out of 100,000 simulations (MonteCarlo analysis). Conclusions: A/B-T is more efficacious and less expensive than standard AT treatment for advanced-stage HL patients, therefore the routine use of interim-PET is warranted in treatment planning and chemosensitivity adapting in these patients. Disclosures: Off Label Use: The study includes use of Rituximab as maintenance in responding patients after first line chemoimmunotherapy.

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Brentuximab Vedotin Combined with ABVD or AVD for Patients with Newly Diagnosed Advanced Stage Hodgkin Lymphoma: Long Term Outcomes

Blood ◽

10.1182/blood.v124.21.292.292 ◽

2014 ◽

Vol 124 (21) ◽

pp. 292-292 ◽

Cited By ~ 11

Author(s):

Joseph M Connors ◽

Stephen Ansell ◽

Steven I. Park ◽

Michelle A. Fanale ◽

Anas Younes

Keyword(s):

Hodgkin Lymphoma ◽

Research Funding ◽

Response Rate ◽

Phase 1 ◽

Brentuximab Vedotin ◽

Advanced Stage ◽

Newly Diagnosed ◽

Genetics Research

Background: The ABVD regimen containing doxorubicin, bleomycin, vinblastine, and dacarbazine is a common standard of care for the frontline treatment of advanced stage Hodgkin lymphoma (Santoro 1987; Duggan 2003) and is curative for the majority of patients; however, up to 30% of patients require a secondary therapy. Hodgkin Reed-Sternberg cells of classical HL (cHL) typically express CD30. In a pivotal phase 2 trial brentuximab vedotin (A, ADCETRIS®), comprised of an anti-CD30 monoclonal antibody conjugated by a protease-cleavable linker to a microtubule-disrupting agent, monomethyl auristatin E (MMAE) induced an objective response rate (ORR) of 75% and complete response rate (CR) of 34% in highly treatment-refractory patients with cHL (Younes 2012). Methods: We conducted a phase 1, open-label, multicenter study to evaluate the safety and efficacy of A when administered in combination with standard therapy (ABVD) or the same regimen without bleomycin (AVD) (Younes 2013). Adult patients with newly diagnosed advanced stage (II bulky, II B, III or IV; 80% stage III or IV) received doses of 0.6, 0.9, or 1.2 mg/kg A with standard doses of ABVD or 1.2 mg/kg with AVD, depending on cohort assignment on Days 1 and 15 of each 28-day cycle for up to 6 cycles of therapy. Previously we reported that among patients assessable for response 95% of patients given ABVD+A achieved a CR, as did 96% of patients given AVD+A. None of 26 patients given AVD+A but 11 of 25 (44%) given ABVD+A experienced pulmonary toxicity, including 2 deaths, establishing that A cannot be safely combined with bleomycin. In this current study we provide the long term survival and safety data on patients enrolled in the phase 1 trial. Results: In total 51 patients were assigned to either ABVD+A (n=25) or AVD+A (n=26). 1 patient who withdrew from the trial during the first cycle of ABVD+A is excluded from this analysis and 1 patient who received 3 cycles of ABVD+A, then withdrew, then received 3 cycles of ABVD alone and 2 patients who died during treatment (pulmonary toxicity) are included (total n=50). Median follow-up from diagnosis for the 24 patients treated with ABVD+A is 41 months (range 9-51 months) and for the 26 patients treated with AVD+A, 31 months (range 9-35 months). All 26 patients treated with AVD+A have been followed longer than the longest time to relapse (7 months). 45 patients remain in first CR and 5 treatment failures have occurred: 4 in the ABVD+A cohort (2 toxic deaths; 2 relapses (9 and 23 months from diagnosis)) and 1 after AVD+A (7 months from diagnosis). 3y-failure-free survival (3y-FFS) is 83% and 96% for ABVD+A and AVD+A, respectively, and 3y-overall survival (3y-OS), is 92% and 100%. No additional toxic deaths have occurred in follow-up. Conclusions: These updated outcomes reflecting the impact of adding brentuximab vedotin (1.2 mg/kg) to standard doses of AVD for classical Hodgkin lymphoma, demonstrating 96% 3y-FFS and 100% 3y-OS with no major unexpected toxicity, strongly support the current large international trial comparing AVD-A (AVD+1.2mg/kg brentuximab vedotin) to standard ABVD (ECHELON-1, clinicaltrials.gov NCT01712490), which may identify a new, less toxic gold standard treatment for advanced stage classical Hodgkin lymphoma. Disclosures Connors: Seattle Genetics: Research Funding. Off Label Use: brentuximab vedotin in phase 1 trial. Ansell:Seattle Genetics: Research Funding. Park:Seattle Genetics: Research Funding; Millennium/Takeda: Research Funding. Fanale:Seattle Genetics: Research Funding. Younes:Seattle Genetics: Research Funding; Millennium/Takeda: Research Funding.

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