Response-adapted frontline therapy for Hodgkin lymphoma: are we there yet?

Abstract Treating Hodgkin lymphoma by using chemotherapy with or without radiotherapy is highly successful, with substantially fewer deaths from lymphoma than from other causes in recent studies of both early-stage and advanced-stage disease. Long-term toxicity is a major consideration in this context, and recent trials have used functional imaging with [18F]fluorodeoxyglucose (FDG) positron emission tomography early in the course of treatment (interim PET) to assess response and modulate subsequent therapy. In early-stage disease, this has allowed omission of consolidation radiotherapy after a good response to doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) chemotherapy, and trials have shown that this can be done without detriment to overall survival, despite a small increase in rates of recurrence of ∼5%. Conversely, escalation to more intensive chemotherapy with bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP) for those with positive interim PET scans seems to be an effective strategy with improved disease control. In advanced-stage disease, several groups have elected to start treatment with ABVD and escalate to BEACOPP or myeloablative therapy for patients who remain PET positive after 2 cycles, which gives rates of disease control of ∼65%. De-escalation by omission of bleomycin and consolidation radiotherapy after a negative interim PET scan seems safe with no increase in recurrence rate, but the performance of interim PET after ABVD is suboptimal, especially for those with very advanced disease at presentation; recurrence rates after a negative scan are ∼15%. The negative predictive value of PET is higher after escalated BEACOPP chemotherapy, and the approach of initially treating with BEACOPP and de-escalating to ABVD for those with negative interim PET scans shows promising early results. Response-adapted therapy has yielded important results for patients with Hodgkin lymphoma and is becoming established as a standard approach.

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The Prognostic Value of Interim PET Scan in Patients with Classical Hodgkin Lymphoma

Blood ◽

10.1182/blood.v120.21.1529.1529 ◽

2012 ◽

Vol 120 (21) ◽

pp. 1529-1529

Author(s):

Yasuhiro Oki ◽

Hubert Chuang ◽

Beth Chasen ◽

Tinsu Pan ◽

Michelle A. Fanale ◽

...

Keyword(s):

Clinical Trials ◽

Prognostic Value ◽

Early Stage ◽

Treatment Decisions ◽

Pet Scan ◽

Advanced Stage ◽

Early Stage Disease ◽

Interim Pet ◽

Stage Disease ◽

Pet Scans

Abstract Abstract 1529 The interim PET scan has prognostic value in pts with cHL. Because the outcome of ptswho have positive interim PET scans was dismal in previous reports, multiple clinical trials are ongoing using the interim PET to guide treatment decisions, but these are mostly non-randomized studies. We performed a retrospective study analyzing the prognostic role of the interim PET scan for predicting event free survival (EFS) for early stage (I and II non-bulky) and advanced stage (II-bulky, III and IV) cHL treated with standard ABVD with or without radiation therapy. This study was approved by the institutional review board. Interim PET results (positive or negative) were collected from the clinical reports of PET scans which were based on visual interpretation. A total of 327 pts diagnosed between 01/2001 and 05/2011, and had interim PET scan after 2 (PET2; n=231) or 3 (PET3; n=96) cycles were reviewed. The median follow up duration of surviving pts was 45 months (range 2–130 months). For pts with advanced stage disease, 5-year EFS rates in PET2-negative (n=79) and PET2-positive (n=20) groups were 75% and 54%, respectively (p=0.027). For pts with low IPS scores (0–2), 5-year EFS rates in PET2-negative (n=60) and PET2-positive (n=15) groups were 77% and 53%, respectively (p=0.02). For pts with high IPS scores (3–7), 5-year EFS rates in PET2-negative (n=19) and PET2-positive (n=5) groups were 69% and 50%, respectively (p=0.76). In pts with early stage disease, 5-year EFS rates in PET2-negative (n=107) and PET2-positive (n=25) groups were 98% and 65%, respectively (p<0.01). PET3 had little prognostic value for EFS for pts with early stage or advanced stage diseases, though the number of pts analyzed was smaller. There have been significant changes in PET technology, methodology, and interpretation criteria. To minimize these factors, we next selected 118 pts whose PET2 were performed between 03/2008 and 05/2011. The PET scans from theres patients were blindly and independently re-reviewed without information on clinical outcome, by two nuclear radiologist based on Deauville criteria. For pts with advanced stage disease, 2-year EFS rates for pts with negative PET2 (n=47) and positive PET2 (n=5) scans were 68% and 60%, respectively (p=0.59). For pts with early stage diseases, 2-year EFS rates for pts with negative PET2 (n=55) and positive PET2 (n=11) scans were 98% and 47%, respectively (p<0.01). In conclusion, this study confirmed that PET2 results remain prognostic, not only for advanced stage disease but more significantly for early stage cHL. However, pts with advanced stage disease whose PET2 was positive had 5-year EFS of 54% (2001–2011), which seems far better than previous reports. Interim-PET guided treatment decisions are not currently recommended outside of clinical trials. Randomized trials will be required to determine whether change of therapy based on PET2 status will improve treatment outcome. Disclosures: Fanale: MedImmune: Research Funding.

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The Prognostic Role of Interim PET after First Chemotherapy Cycle and PET Sequential Evaluation of Response to ABVD in Hodgkin Lymphoma Patients - the Polish Lymphoma Research Group (PLRG) Observational Study

Blood ◽

10.1182/blood.v126.23.3943.3943 ◽

2015 ◽

Vol 126 (23) ◽

pp. 3943-3943 ◽

Cited By ~ 4

Author(s):

Jan M Zaucha ◽

Bogdan Malkowski ◽

Edyta Subocz ◽

Stephane Chauvie ◽

Joanna Tajer ◽

...

Keyword(s):

Observational Study ◽

Disease Progression ◽

Hodgkin Lymphoma ◽

Research Funding ◽

Early Stage ◽

Advanced Stage ◽

Prognostic Role ◽

Interim Pet ◽

Pet Scans

Abstract Background: Several studies confirmed the predictive role on treatment outcome of interim-PET after 2nd ABVD cycle (iPET2) in Hodgkin lymphoma (HL). We hypothesized that interim PET after 1st cycle (iPET1) might define chemosensitivity with a better accuracy than iPET-2. To test this hypothesis, PLRG launched in 2008 a prospective multicenter observational study aiming at assessing the prognostic role of iPET1 and the dynamic of sequential PET response to ABVD. Methods: Adult pts with newly diagnosed early (stage I-IIA) and advanced (stage IIB-IV) consecutively enrolled in 11 Polish centers were risk-stratified by the EORTC/GELA criteria and treated according to the ESMO guidelines: ABVD x 3-4 cycles + IFRT in early stage, ABVD x 6 ± consolidation RT in advanced stage disease. Patients were scanned with iPET1 and iPET2 and no treatment change was permitted based solely on iPET results, with the exception of clinical or radiological evidence of overt HL progression. After the first interim analysis (52 pts enrolled, 2010), which demonstrated that all the iPET1 negative patients had also a negative iPET2, the protocol was amended, limiting the iPET2 scans only to pts with iPET1 Deauville score 5,4,3. Quality control for PET-CT was supervised by the Italian-Polish core lab using a standard methodology. PET scans were interpreted locally according to the Deauville 5-point scale: Score 1 to 3, was considered a negative (-), score 4 to 5 a positive (+) scan. Subsequently all PET scans were uploaded to the web platform WIDEN® for central review and Italian-Polish expert panel (EP) scored them afresh. Discorcondant cases were discussed in a joint review session with all the five EP members. Binary and overall concordance rates were calculated using k Cohen's and alpha Krippendorf's coefficients, respectively. Negative (NPV) and positive predictive values (PPV) of iPET1 were calculated using time to progression free survival (PFS) event. Results: Between 2008 and 2014, 346 pts were registered. 35 pts were excluded from the analysis for absence/poor quality of images resulting in 108(35%) assessable pts with early and 203(65%) with advanced HL. Median age at diagnosis was 31(18-80) years. iPET1 was scored 1-3 in 87/108(81%), and 4-5 in 21/108(19%) of pts with early and in 133/203(65%), and 70/203(35%) with advanced stage, respectively. Out of 91pts with positive iPET1, 83 pts underwent iPET2, which remained (+) in 41/83(49,4%) pts. In 22 pts treatment was escalated. 11 of those pts, in whom the treatment escalation was decided solely on positive iPET were excluded from the analysis; the remaining had symptoms or CT evidence of progression. After a median follow-up of 40,2 (3,2-90,2) months 300 pts (103 "early" and 197 "advanced") were evaluable. 65(21,7%) of them (9 in early and 56 in advanced group) had a PFS event: in "early" group 9(9%) showed disease progression (4 with iPET1(-) and 5 with IPET1(+)) and 1 of them died. In advanced stage 49(25%) pts showed disease progression (16 with iPET1(-) and 33 withiPET1(+)) out of whom 13 died; 7 additional pts died without HL progression: 4 from toxicity and 3 from unrelated events. At 36 months NPV and PPV of iPET1 was 93% and 45% in "early" and 81% and 52% in "advanced" group, respectively. The dynamic of response to ABVD was assessed in 189 pts who underwent both iPETs. All 116 pts with iPET1(-) remained (-) in iPET2-(fast-responders). Out of 83pts with IPET1(+) 39 (47%) became iPET2(-)-(slow responders); the rest (34pts: 41%) remained iPET2(+)-(no responders). PFS for fast-responders @36 months was 85%, for slow-responders 80% (log rank p=0,36) and for no-responders 25% (log rank p=0,0000). The EP changed the local iPET1 score in 27 cases: in 14 from (+) to (-) in 13 from (-) to (+). The inter-observer-agreement among reviewers on evaluating a positive vs. negative interim PET scans was good, Fleiss' kappa = 0.73, comparable to that found in analogous studies (IVS, HD0607). Conclusion: iPET1 fails to better identify chemosensitivity in ABVD-treated HL compared to iPET2. PPV of iPET1 is substantially inferior to the published results for iPET2. However NPV of iPET1 is comparable to iPET2 and therefore might guide early treatment de-escalation strategies. Disclosures Zaucha: Roche: Honoraria, Research Funding, Speakers Bureau; Amgen: Honoraria, Research Funding, Speakers Bureau; Takeda: Honoraria, Speakers Bureau. Knopinska-Posluszny:Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen: Speakers Bureau; Teva: Other: travel, accommodation, Speakers Bureau. Walewski:Mundipharma; Roche; Takeda: Honoraria, Other: Travel expenses; Amgen; Boehringer Ingelheim; Celgene; Janssen-Cilag; Mundipharma; Roche; Takeda; Teva: Consultancy; Bayer (Inst); Bayer/Onyx (Inst); Boehringer Ingelheim (Inst); Celgene (Inst); Celltrion (Inst); Gilead Sciences (Inst); GlaxoSmithKline (Inst); GlaxoSmithKline (Inst); Mundipharma (Inst); Pfizer (Inst); Roche (Inst); Roche/Genentech (Inst); Seattle Geneti: Research Funding.

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Evaluation of treatment outcome in 175 patients with Hodgkin lymphoma aged 60 years or over: the SHIELD study

Blood ◽

10.1182/blood-2011-12-396556 ◽

2012 ◽

Vol 119 (25) ◽

pp. 6005-6015 ◽

Cited By ~ 61

Author(s):

Stephen J. Proctor ◽

Jennifer Wilkinson ◽

Gail Jones ◽

Gillian C. Watson ◽

Helen H. Lucraft ◽

...

Keyword(s):

Hodgkin Lymphoma ◽

Cox Regression ◽

Early Stage ◽

Univariate Analysis ◽

Central Element ◽

Disease Stage ◽

Advanced Stage ◽

Early Stage Disease ◽

Large Patient ◽

Stage Disease

Abstract The SHIELD program for Hodgkin lymphoma in patients 60 years of age or older, prospectively evaluated clinical features and outcome in a large patient cohort (n = 175). The central element was a phase 2 study of VEPEMB chemotherapy (n = 103, median age 73 years) incorporating comorbidity assessment. A total of 72 other patients were treated off-study but registered prospectively and treated concurrently with: ABVD (n = 35); CLVPP (n = 19), or other (n = 18). Of VEPEMB patients, 31 had early-stage disease (stage 1A/2A) and received VEPEMB 3 times plus radiotherapy. Median follow-up was 36 months. Complete remission (CR) rate (intention-to-treat) was 74% and 3-year overall survival (OS) and progression-free survival (PFS) were 81% and 74%, respectively. A total of 72 patients had advanced-stage disease (stage 1B/2B/3 or 4) and received VEPEMB 6 times. CR rate was 61% with 3-year OS and PFS of 66% and 58%, respectively. Of patients achieving CR, 13% with early-stage and 5% with advanced-stage disease progressed. Overall treatment-related mortality was 7%. In patients treated with curative intent with VEPEMB, ABVD, and CLVPP (n = 157), CR linked to several factors in univariate analysis. In a Cox regression model only, obtaining CR remained significant for OS and CR plus comorbidity and age for PFS. RS-EBV status had no significant effect on outcome.

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HODGKIN LYMPHOMA IN OLDER PATIENTS: AN ORPHAN DISEASE?

Mediterranean Journal of Hematology and Infectious Diseases ◽

10.4084/mjhid.2014.050 ◽

2014 ◽

Vol 6 (1) ◽

pp. e2014050 ◽

Cited By ~ 10

Author(s):

Antoine Thyss ◽

Esma Saada ◽

Lauris Gastaud ◽

Frédéric Peyrade ◽

Daniel Ré

Keyword(s):

Hodgkin Lymphoma ◽

Prospective Studies ◽

Older Patients ◽

Early Stage ◽

The Elderly ◽

Study Group ◽

Advanced Stage ◽

Early Stage Disease ◽

Younger Patients ◽

Stage Disease

Hodgkin Lymphoma HL ica be cured in the large majority of younger patients, but prognosis for older patients, especially those with advanced-stage disease, has not improved substantially. The percentage of HL patients aged over 60 ranges between 15% and 35%.A minority of them is enrolled into clinical trials. HL in the elderly have some specificities: more frequent male sex, B-symptoms, advanced stage, sub diaphragmatic presentation, higher percentage of mixed cellularity, up to 50% of advanced cases associated to EBV. Very old age (>70) and comorbidities are factor of further worsening prognosis. Like in younger patients, ABVD is the most used protocol, but treatment outcome remains much inferior with more frequent, severe and sometimes specific toxicities. Few prospective studies with specific protocols are available. The main data have been published by the Italian Lymphoma Group with the VEPEMB schedule and the German Hodgkin Study Group with the PVAG regimen. Recently, the Scotland and Newcastle Lymphoma Study Group published the SHIELD program associating a prospective phase 2 trial with VEPEMB and a prospective registration of others patients. Patients over 60y with early-stage disease received three cycles plus radiotherapy and had 81% of 3-year overall survival (OS).Those with advanced-stage disease received six cycles, with 3-year OS of 66%.The role of geriatric and comorbidity assessment in the treatment’s choice for HL in the elderly is a major challenge. The combination of loss of activities of daily living combined with the age stratification more or less 70y has been shown as a simple and effective survival model. Hopes come from promising new agents like brentuximab-vedotin (BV) a novel antibody-drug conjugate. The use of TEP to adapt the combination of chemotherapy and radiotherapy according to the metabolic response could also be way for prospective studies.

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An Immunohistochemical Score Based On CD68 and FOXP3 Expression In the Tumour Microenvironment at Diagnosis Defines Prognostic Groups In Both Early and Advanced Stage Classical Hodgkin Lymphoma

Blood ◽

10.1182/blood.v116.21.750.750 ◽

2010 ◽

Vol 116 (21) ◽

pp. 750-750 ◽

Cited By ~ 2

Author(s):

Paul Greaves ◽

Andrew James Clear ◽

David Andrew Owen ◽

Finlay Macdougall ◽

Andrew Wilson ◽

...

Keyword(s):

Hodgkin Lymphoma ◽

Early Stage ◽

Prognostic Significance ◽

Automated Image Analysis ◽

Advanced Stage ◽

Classical Hodgkin Lymphoma ◽

Early Stage Disease ◽

Stage Disease ◽

Prognostic Groups ◽

Good Risk

Abstract Abstract 750 The non-malignant immune infiltrate comprises the bulk of pathologic tissue in classical Hodgkin lymphoma (CHL). This microenvironment has the potential to induce both malignant cell suppression and support. Increased macrophage infiltration assessed by CD68 expression has been shown to confer adverse prognostic significance (Steidl et al. N Engl J Med, 2010; 362:875-85) while increased FOXP3 expressing T cells are beneficial in this disease (Tzankov et al. Haematologica, 2008; 93: 193–200). However no histological score routinely leads to modification of treatment. Assessing outcomes by the parameters of overall survival (OS), disease specific survival (DSS) and freedom from first line treatment failure (FFTF) at 5 years in a cohort of patients treated at St Bartholomew's Hospital (Barts), London we developed a prognostic score based upon expression of both FOXP3 and CD68 in the CHL microenvironment which defined poor and good risk groups in both early (Stages I and IIA) and advanced stage disease, including a 'poor risk' early stage group with 25% FFTF and a ‘good risk' advanced stage group with 90% FFTF. Immunohistochemical analysis was performed on tissue microarrays (TMAs) from previously untreated patients' diagnostic lymph node biopsies in whom clinical outcome was available. From all 1056 adult patients with HL diagnosed at Barts between 1972 and 2005, high quality formalin-fixed paraffin-embedded tissue was available for 122 (12%), with characteristics representative of the whole group. Median age of the 122 patients was 30 (range 18–80) years, 35% female, 71% advanced stage with median follow up 16.5 (range 2–40) years. Triplicate cores were made from areas of high cellularity, containing malignant cells and avoiding fibrotic, acellular portions, arrayed onto glass slides and stained immunohistochemically for FOXP3 or CD68. Absolute and proportional numbers of FOXP3+ nuclei and CD68+ cell bodies were counted across all intact cores using an automated image analysis system (Ariol), confirmed by expert histopathologists, and means calculated and corrected to a single high powered field (hpf). Recursive partitioning was used to generate optimal cutoff values discriminating prognostic groups and comparisons performed by the chi-square test. Using cutoffs of <5%, 5–15% and >15% to define low, intermediate and high CD68 density, 3 prognostic groups were defined, the favourable group having the lowest CD68+ density. OS for low, intermediate and high groups were 89%, 80% and 65% respectively (p=0.02), with FFTF 82%, 64% and 29% (p=0.001). Prognostic significance was maintained in subgroups presenting with advanced stage (FFTF 73%, 63% and 33%, p=0.03), as well as early stage disease (FFTF 92%, 70% and 20%, p=0.01). Using cutoffs of <12.5, 12.5–50 and >50 nuclei/hpf to define low, intermediate and high FOXP3+ cell density, 3 prognostic groups were defined, the favourable group having the highest FOXP3+ density. OS for low, intermediate and high groups were 68%, 80% and 94% respectively (p=0.006), with FFTF 50%, 62%, and 84% (p=0.002). Prognostic significance was maintained for both advanced (FFTF: 48%, 60% and 72%, p=0.04) and early stage disease (FFTF: 57%, 67% and 100%, p=0.04). A combined ‘FOXP3/CD68 score' derived from the patient's prognostic group for both markers, for which suitable cores were available on 98 patients, further improved the predictive value of each individually (See Figure). In this model, favourable, intermediate and unfavourable groups had 5 year FFTF of 93%, 62% and 47% (p=0.0002), DSS 93%, 82% and 63% (p=0.03) and OS 93%, 82% and 59% (p=0.002). The score retained prognostic significance for 5 year FFTF and OS in the subgroup of patients presenting with advanced (FFTF: 90%, 59% and 46%, p=0.008; OS: 90%, 80% and 54%, p=0.004) as well as early stage disease (FFTF: 100%, 71% and 25%, p=0.005; OS: 100%, 82% and 75%, trend only, p=ns). We conclude that FOXP3 and CD68 are important independent factors, which in combination have considerable predictive power and will now be validated prospectively. Disclosures: No relevant conflicts of interest to declare.

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Controversies in the Management of Early-Stage Hodgkin Lymphoma

Journal of the National Comprehensive Cancer Network ◽

10.6004/jnccn.2020.5033 ◽

2020 ◽

Vol 18 (12.5) ◽

pp. 1748-1750

Author(s):

Ranjana H. Advani

Keyword(s):

Hodgkin Lymphoma ◽

Early Stage ◽

Fine Tuning ◽

Early Stage Disease ◽

Careful Patient ◽

Interim Pet ◽

Stage Disease ◽

Selection For ◽

Number Of Treatment ◽

Sheer Number

Early-stage Hodgkin lymphoma is a highly curable malignancy, but controversies surrounding treatment recommendations persist due to the sheer number of treatment choices available, as well as the effort to balance risk versus benefit for each individual patient. The gold standard for treatment has evolved over the years. Currently, in the PET era, fine-tuning therapy approaches is largely focused on avoiding giving too much therapy to patients with a negative interim PET and too little therapy to those with a positive interim PET. Careful patient selection for therapy has become increasingly important, as patient risk factors for early-stage disease are variably defined by German Hodgkin Study Group, EORTC, and NCCN criteria.

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Lymphocyte-predominant Hodgkin lymphoma: what is the optimal treatment?

Hematology ◽

10.1182/asheducation-2013.1.406 ◽

2013 ◽

Vol 2013 (1) ◽

pp. 406-413 ◽

Cited By ~ 9

Author(s):

Michelle Fanale

Keyword(s):

B Cell ◽

Hodgkin Lymphoma ◽

Radiation Treatment ◽

Early Stage ◽

B Cell Lymphoma ◽

B Cell Lymphomas ◽

Early Stage Disease ◽

Stage Disease ◽

Relapsed Disease

AbstractNodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a unique diagnostic entity, with only ∼ 500 new cases in the United States per year with a similar infrequent incidence worldwide. NLPHL also has distinctive pathobiology and clinical characteristics compared with the more common classical Hodgkin lymphoma (cHL), including CD20 positivity of the pathognomic lymphocytic and histiocytic cells and an overall more indolent course with a higher likelihood of delayed relapses. Given the limited numbers of prospective NLPHL-focused trials, management algorithms historically have typically been centered on retrospective data with guidelines often adopted from cHL and indolent B-cell lymphoma treatment approaches. Key recent publications have delineated that NLPHL has a higher level of pathological overlap with cHL and the aggressive B-cell lymphomas than with indolent B-cell lymphomas. Over the past decade, there has been a series of NLPHL publications that evaluated the role of rituximab in the frontline and relapsed setting, described the relative incidence of transformation to aggressive B-cell lymphomas, weighed the benefit of addition of chemotherapy to radiation treatment for patients with early-stage disease, considered what should be the preferred chemotherapy regimen for advanced-stage disease, and even assessed the potential role of autologous stem cell transplantation for the management of relapsed disease. General themes within the consensus guidelines include the role for radiation treatment as a monotherapy for early-stage disease, the value of large B-cell lymphoma–directed regimens for transformed disease, the utility of rituximab for treatment of relapsed disease, and, in the pediatric setting, the role of surgical management alone for patients with early-stage disease.

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Balancing risk and benefit in early-stage classical Hodgkin lymphoma

Blood ◽

10.1182/blood-2017-10-772665 ◽

2018 ◽

Vol 131 (15) ◽

pp. 1666-1678 ◽

Cited By ~ 12

Author(s):

Paul J. Bröckelmann ◽

Stephanie Sasse ◽

Andreas Engert

Keyword(s):

Disease Control ◽

Hodgkin Lymphoma ◽

Early Stage ◽

Therapeutic Option ◽

Classical Hodgkin Lymphoma ◽

Excellent Outcome ◽

Limited Stage ◽

Interim Pet ◽

Increased Risk

Abstract With defined chemotherapy and radiotherapy (RT) and risk-adapted treatment, early-stage classical Hodgkin lymphoma (HL) has become curable in a majority of patients. Hence, a major current goal is to reduce treatment-related toxicity while maintaining long-term disease control. Patients with early-stage favorable disease (ie, limited stage without risk factors [RFs]) are frequently treated with 2 cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (2×ABVD) followed by 20-Gy involved-field or involved-site RT (IF/ISRT). In patients with early-stage unfavorable disease (ie, limited stage with RFs), 4 cycles of chemotherapy are usually consolidated with 30-Gy IF/ISRT. Compared with 4×ABVD, 2 cycles of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (2×BEACOPPescalated) followed by 2×ABVD improved 5-year progression-free survival (PFS), with similar 5-year overall survival. Recently, treatment strategies based on [18F]fluorodeoxyglucose positron emission tomography (PET) response were evaluated. In early-stage unfavorable HL, a majority of patients achieved a negative interim PET after 2×ABVD and an excellent outcome after 4×ABVD, whereas in those with a positive interim PET, 2×BEACOPPescalated improved 5-year PFS. Furthermore, a PET-guided RT approach was evaluated to decrease long-term toxicity. Although both the RAPID and H10 trials reported poorer disease control without RT, PET-guided omission of RT can constitute a valid therapeutic option in patients with an increased risk of RT-associated toxicity (eg, because of sex, age, or disease localization). Implementation of drugs such as the anti-CD30 antibody-drug conjugate brentuximab vedotin or the anti–programmed death 1 antibodies nivolumab or pembrolizumab might allow further reduction of overall mortality and improve quality of life in affected patients.

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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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Neuroendocrine carcinoma of the cervix: A single institution’s experience.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.e15585 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. e15585-e15585

Author(s):

Megan Preston ◽

Georgia Anne-Lee McCann ◽

David M. O'Malley ◽

Christina Boutsicaris ◽

Larry J. Copeland ◽

...

Keyword(s):

Adjuvant Therapy ◽

Metastatic Disease ◽

Survival Data ◽

Early Stage ◽

Stage I ◽

Stage Ii ◽

Advanced Stage ◽

Single Institution ◽

Early Stage Disease ◽

Stage Disease

e15585 Background: Neuroendocrine carcinomas (NEC) of the cervix comprise only 2% of all cervical cancers. As a result, prospective data is limited and treatment guidelines rely on literature from lung NEC. The objective of this study was to examine and report on our experience in the management of this rare, aggressive disease. Methods: This was an IRB-approved, single-institution, retrospective review. Study criteria included patients with cervical NEC diagnosed between 1990-2011. Demographic, treatment and survival data was collected. Progression-free survival (PFS) and overall survival (OS) was defined as the time from date of initial treatment until progression or death respectively, or date of last contact. Results: A total of 24 patients met inclusion criteria. The median age at diagnosis was 43. Median PFS was 13.6 months and median OS was 16.4 months. The majority of patients had advanced-stage disease (61% stage II-IV, 39% stage I). Of the 9 patients with stage I disease, 4 were treated with platinum + etoposide-based neoadjuvant chemotherapy and 5 were treated with initial radical surgery. Seven of the 9 patients had post-operative adjuvant therapy consisting of chemotherapy, chemo-radiation or radiation only. Seven of the 9 patients (78%) were alive at last follow-up. Of the two patients who were deceased, one had metastatic disease found at surgery and the other declined adjuvant therapy and died of recurrence. Patients with stage II-IV disease (n=15) had a median PFS and OS of 11.5 and 12.1 months, respectively. Only 2 had no evidence of disease at last encounter. The remainder died without achieving remission. Patients with metastatic disease had significantly worse survival when compared to those with loco-regional disease with a median OS of 8 vs. 28 months (p = .03), respectively. Conclusions: We report one of the largest single-institution experiences of neuroendocrine cervical cancer. Advanced-stage patients had a poor prognosis regardless of therapy. However, multi-modality therapy in early-stage disease resulted in an excellent prognosis (78% survival) for these rare, highly aggressive tumors. These findings support the goal of curative intent for early-stage disease using multi-modality therapy.

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