Irradiating Residual Disease to 30 Gy with Proton Therapy in Pediatric Mediastinal Hodgkin Lymphoma

Abstract Background Local relapse is a predominant form of recurrence among pediatric patients with Hodgkin lymphoma (PHL). Although PHL radiotherapy doses have been approximately 20 Gy, adults with Hodgkin lymphoma receiving 30 to 36 Gy experience fewer in-field relapses. We investigated the dosimetric effect of such a dose escalation to the organs at risk (OARs). Materials and Methods Ten patients with PHL treated with proton therapy to 21 Gy involved-site radiation therapy (ISRT21Gy) were replanned to deliver 30 Gy by treating the ISRT to 30 Gy (ISRT30Gy), delivering 21 Gy to the ISRT plus a 9-Gy boost to postchemotherapy residual volume (rISRTboost), and delivering 30 Gy to the residual ISRT target only (rISRT30Gy). Radiation doses to the OARs were compared. Results The ISRT30Gy escalated the dose to the target by 42% but also to the OARs. The rISRTboost escalated the residual target dose by 42%, and the OAR dose by only 17% to 26%. The rISRT30Gy escalated the residual target dose by 42% but reduced the OAR dose by 25% to 46%. Conclusion Boosting the postchemotherapy residual target dose to 30Gy can allow for dose escalation with a slight OAR dose increase. Treating the residual disease for the full 30Gy, however, would reduce the OAR dose significantly compared with ISRT21Gy. Studies should evaluate these strategies to improve outcomes and minimize the late effects.

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Feasibility of Deep Inspiratory Breath Hold in Pediatric Patients Receiving Proton Therapy for Hodgkin Lymphoma Patients to Decrease Radiation Dose to Organs at Risk

International Journal of Radiation Oncology*Biology*Physics ◽

10.1016/j.ijrobp.2020.07.1527 ◽

2020 ◽

Vol 108 (3) ◽

pp. e242

Author(s):

A.S. Grewal ◽

E.R. Cummings ◽

R. Battaglini ◽

D. Geary ◽

M. Eishenhower ◽

...

Keyword(s):

At Risk ◽

Radiation Dose ◽

Hodgkin Lymphoma ◽

Proton Therapy ◽

Pediatric Patients ◽

Organs At Risk ◽

Breath Hold

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Development and Implementation of Proton Therapy for Hodgkin Lymphoma: Challenges and Perspectives

Cancers ◽

10.3390/cancers13153744 ◽

2021 ◽

Vol 13 (15) ◽

pp. 3744

Author(s):

Pierre Loap ◽

Ludovic De Marzi ◽

Alfredo Mirandola ◽

Remi Dendale ◽

Alberto Iannalfi ◽

...

Keyword(s):

At Risk ◽

Radiation Therapy ◽

Hodgkin Lymphoma ◽

Proton Therapy ◽

Early Stage ◽

Organs At Risk ◽

Intensity Modulated Radiation Therapy ◽

Progression Free Survival ◽

Treatment Techniques ◽

Increased Risk

Consolidative radiation therapy for early-stage Hodgkin lymphoma (HL) improves progression-free survival. Unfortunately, first-generation techniques, relying on large irradiation fields, were associated with an increased risk of secondary cancers, and of cardiac and lung toxicity. Fortunately, the use of smaller target volumes combined with technological advances in treatment techniques currently allows efficient organs-at-risk sparing without altering tumoral control. Recently, proton therapy has been evaluated for mediastinal HL treatment due to its potential to significantly reduce the dose to organs-at-risk, such as cardiac substructures. This is expected to limit late radiation-induced toxicity and possibly, second-neoplasm risk, compared with last-generation intensity-modulated radiation therapy. However, the democratization of this new technique faces multiple issues. Determination of which patient may benefit the most from proton therapy is subject to intense debate. The development of new effective systemic chemotherapy and organizational, societal, and political considerations might represent impediments to the larger-scale implementation of HL proton therapy. Based on the current literature, this critical review aims to discuss current challenges and controversies that may impede the larger-scale implementation of mediastinal HL proton therapy.

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Advancing the Therapeutic Index of Pediatric Patients with Stage III and IV Hodgkin Lymphoma with Proton Therapy

Klinische Pädiatrie ◽

10.1055/s-0034-1371125 ◽

2014 ◽

Vol 226 (02) ◽

Author(s):

B Hoppe ◽

A Holtzman ◽

Z Li ◽

Z Su ◽

W Slayton ◽

...

Keyword(s):

Hodgkin Lymphoma ◽

Proton Therapy ◽

Pediatric Patients ◽

Therapeutic Index ◽

Stage Iii

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Assessment of Radiation Doses Delivered to Organs at Risk Among Patients With Early-Stage Favorable Hodgkin Lymphoma Treated With Contemporary Radiation Therapy

JAMA Network Open ◽

10.1001/jamanetworkopen.2020.13935 ◽

2020 ◽

Vol 3 (9) ◽

pp. e2013935

Author(s):

Chelsea C. Pinnix ◽

Jillian R. Gunther ◽

Penny Fang ◽

Mikaela E Bankston ◽

Sarah A. Milgrom ◽

...

Keyword(s):

At Risk ◽

Radiation Therapy ◽

Hodgkin Lymphoma ◽

Early Stage ◽

Organs At Risk ◽

Radiation Doses

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Current Situation of Proton Therapy for Hodgkin Lymphoma: From Expectations to Evidence

Cancers ◽

10.3390/cancers13153746 ◽

2021 ◽

Vol 13 (15) ◽

pp. 3746

Author(s):

Pierre Loap ◽

Alfredo Mirandola ◽

Ludovic De Marzi ◽

Remi Dendale ◽

Alberto Iannalfi ◽

...

Keyword(s):

Hodgkin Lymphoma ◽

Proton Therapy ◽

First Generation ◽

Current Practice ◽

Early Stage ◽

Organs At Risk ◽

Progression Free Survival ◽

Late Toxicity ◽

Second Neoplasm ◽

Free Survival

Consolidative radiation therapy (RT) is of prime importance for early-stage Hodgkin lymphoma (HL) management since it significantly increases progression-free survival (PFS). Nevertheless, first-generation techniques, relying on large irradiation fields, delivered significant radiation doses to critical organs-at-risk (OARs, such as the heart, to the lung or the breasts) when treating mediastinal HL; consequently, secondary cancers, and cardiac and lung toxicity were substantially increased. Fortunately, HL RT has drastically evolved and, nowadays, state-of-the-art RT techniques efficiently spare critical organs-at-risks without altering local control or overall survival. Recently, proton therapy has been evaluated for mediastinal HL treatment, due to its possibility to significantly reduce integral dose to OARs, which is expected to limit second neoplasm risk and reduce late toxicity. Nevertheless, clinical experience for this recent technique is still limited worldwide. Based on current literature, this critical review aims to examine the current practice of proton therapy for mediastinal HL irradiation.

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Ten-year results of a German Hodgkin Study Group randomized trial of standard and increased dose BEACOPP chemotherapy for advanced Hodgkin lymphoma (HD9)

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.lba8015 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. LBA8015-LBA8015 ◽

Cited By ~ 6

Author(s):

V. Diehl ◽

J. Franklin ◽

B. Pfistner ◽

A. Engert

Keyword(s):

Overall Survival ◽

Hodgkin Lymphoma ◽

Dose Escalation ◽

Residual Disease ◽

Standard Dose ◽

Survival Rates ◽

Secondary Malignancy ◽

Tumor Control ◽

Group Randomized Trial

LBA8015 Background: The HD9 trial was designed to compare standard and dose escalated versions of a novel chemotherapy BEACOPP in advanced Hodgkin lymphoma. The previous analysis in 2004 showed improved tumor control and overall survival due to dose escalation. The present 10 year analysis in March 2007 aimed to update and confirm these results and to monitor late effects. Methods: Patients aged 16–65 years with untreated Hodgkin lymphoma stage IIB/IIIA and risk factors or stage IIIB/IV were randomized to (A) 4 double cycles COPP/ABVD, (B) 8 cycles standard-dose BEACOPP or (C) 8 cycles increased-dose BEACOPP (doxorubicin, cyclophosphamide and etoposide at 140%, 192% and 200% of standard doses, respectively), each followed by irradiation of initial bulky and residual disease. Accrual of at least 900 patients was planned so as to detect a 9–10% improvement in the primary endpoint, freedom from treatment failure (FFTF), with a power of 80% (alpha=5%). Results: 1196 of 1201 eligible, randomized patients were evaluable (261, 469 and 466 in arms A, B and C, respectively). Median follow-up times were 122, 111 and 107 months in arms A, B and C respectively (29–32 months longer than in 2004). Corresponding 10-year FFTF rates were 64%, 70% and 82% respectively (p<0.0001). FFTF was significantly better in the increased-dose arm than in the standard-dose arm (p<0.0001). 10-year overall survival rates were 75%, 80% and 86% respectively (p=0.0005). Overall survival was also significantly better in the increased-dose arm than in the standard-dose arm (p=0.0053). Death due to HL was 11.5%, 8.1% and 2.8% in arms A, B and C respectively. 74 second malignancies were documented: 1, 7 and 14 acute myeloid leukemias (AML); 7, 8 and 5 non-Hodgkin lymphomas; 7, 16 and 9 solid tumors/others in arms A, B and C respectively. The corresponding overall secondary malignancy rates were 6.7% , 8.9% and 6.8%. Conclusions: Even after 10 years, dose escalation of BEACOPP chemotherapy results in a stabilized significant improvement in long-term FFTF and OS rates. The risk of secondary AML, although increased in this study after increased-dose BEACOPP, amounts to 0.9% in the succeeding study with increased BEACOPP with 1502 patients and 4 years median follow-up. No significant financial relationships to disclose.

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Monte Carlo (MC)-based volumetric modulated arc therapy (VMAT) in locally advanced esophageal cancer with potential for dose escalation.

Journal of Clinical Oncology ◽

10.1200/jco.2014.32.3_suppl.77 ◽

2014 ◽

Vol 32 (3_suppl) ◽

pp. 77-77

Author(s):

Shaakir Hasan ◽

Anil Sethi ◽

Jennifer Breunig ◽

Gabriel Axelrud ◽

William Small ◽

...

Keyword(s):

Dose Escalation ◽

Organs At Risk ◽

Locally Advanced ◽

Volumetric Modulated Arc Therapy ◽

Intensity Modulated Radiotherapy ◽

Conformal Radiotherapy ◽

Target Volume ◽

Target Dose ◽

Treatment Techniques ◽

Prescription Dose

77 Background: Previous attempts at dose escalation in esophagus radiotherapy (RT), mostly based on older planning techniques, have not shown improved outcomes. We aimed to investigate the importance of newer, sophisticated dose algorithms and treatment techniques in escalating target dose and reducing dose to organs at risk (OAR). Methods: Treatment plans for 10 patients were retrospectively evaluated using 3D conformal radiotherapy (3DCRT), MC based intensity modulated radiotherapy (IMRT), and VMAT. Prescription dose was 45 Gy to the planning target volume (PTV) in 25 fractions followed by a 5.4 Gy boost in 3 fractions. PTV (mean±s.d. = 681±236 cc) were planned with BrainLab iPlan 4.1 software as IMRT and VMAT. Dose distributions were calculated with both pencil beam (PB) and MC algorithms. Each PTV was normalized to receive at least 95% of 50.4 Gy or 60 Gy dose. OARs were evaluated as per RTOG1010 dose guidelines. Paired t-tests were used for statistical analysis. Results: IMRT vs. 3DCRT PTV 50.4 Gy: IMRT plans decreased heart and lung average Dmean by 4.7 Gy (p = 0.053) and 1.9 Gy (p = 0.001) respectively when compared to 3DCRT. In addition, average values of lung V5, V10, and V30 also reduced by 7.1%, 5.5%, and 3.6% respectively (p < 0.05). There was a 12.1% decrease in heart V40 (p=0.053) and 3.7% reduction in liver V30 (p=0.08). PTV 60Gy: IMRT plans at 60 Gy led to lower OAR doses compared to 3DCRT at 50.4 Gy. MC based IMRT results did not significantly differ from PB, with the exception of lung V5 which was 4.4% higher (p <0.001). VMAT vs. IMRT PTV 50.4 Gy: VMAT based planning, compared to IMRT, lowered V20 (3.4%, p=0.029), V30 (1.6%, p = 0.013), and spinal cord Dmax (5.4 Gy, p = 0.001). However, lung Dmean, V5, and V10 increased by 1.2 Gy, 11.7%, 16.7% respectively (p < 0.001). PTV 60 Gy: With VMAT planning, all OAR dose parameters were within the RTOG 1010 limits, although lung V5 and V10 exceeded acceptable limits by 1.6% and 2.6% respectively. Conclusions: Compared to 3DCRT, target dose escalation with IMRT and VMAT is possible with improved OAR dose sparing, as evaluated with MC algorithms. Increased dose values for V5 and V10 as seen in MC based VMAT plans call for reassessment of RTOG 1010 guidelines.

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