Meng Wei Ho

Proton therapy with concomitant capecitabine for pancreatic and ampullary cancers is associated with a low incidence of gastrointestinal toxicity

Abstract Background. To review treatment toxicity for patients with pancreatic and ampullary cancer treated with proton therapy at our institution. Material and methods. From March 2009 through April 2012, 22 patients were treated with proton therapy and concomitant capecitabine (1000 mg PO twice daily) for resected (n = 5); marginally resectable (n = 5); and unresectable/inoperable (n = 12) biopsy-proven pancreatic and ampullary adenocarcinoma. Two patients with unresectable disease were excluded from the analysis for reasons unrelated to treatment. Proton doses ranged from 50.40 cobalt gray equivalent (CGE) to 59.40 CGE. Results. Median follow-up for all patients was 11 (range 5–36) months. No patient demonstrated any grade 3 toxicity during treatment or during the follow-up period. Grade 2 gastrointestinal toxicities occurred in three patients, consisting of vomiting (n = 3); and diarrhea (n = 2). Median weight loss during treatment was 1.3 kg (1.75% of body weight). Chemotherapy was well-tolerated with a median 99% of the prescribed doses delivered. Percentage weight loss was reduced (p = 0.0390) and grade 2 gastrointestinal toxicity was eliminated (p = 0.0009) in patients treated with plans that avoided anterior and left lateral fields which were associated with reduced small bowel and gastric exposure. Discussion. Proton therapy may allow for significant sparing of the small bowel and stomach and is associated with a low rate of gastrointestinal toxicity. Although long-term follow-up will be needed to assess efficacy, we believe that the favorable toxicity profile associated with proton therapy may allow for radiotherapy dose escalation, chemotherapy intensification, and possibly increased acceptance of preoperative radiotherapy for patients with resectable or marginally resectable disease.

Initial Report of a Prospective Dosimetric and Clinical Feasibility Trial Demonstrates the Potential of Protons to Increase the Therapeutic Ratio in Breast Cancer Compared With Photons.

PURPOSE To compare dosimetric endpoints between proton therapy (PT) and conventional radiation and determine the feasibility of PT for regional nodal irradiation (RNI) in women with breast cancer. METHODS AND MATERIALS From 2012 to 2014, 18 women (stage IIA-IIIB) requiring RNI prospectively enrolled on a pilot study. Median age was 51.8 years (range, 42-73 years). The cohort included breast-conserving therapy (BCT) and mastectomy patients and right- and left-sided cancers. Treatment targets and organs at risk were delineated on computed tomography scans, and PT and conventional plans were developed. Toxicity was prospectively recorded using Common Terminology Criteria for Adverse Events version 4.0. A Wilcoxon signed-rank sum test compared the dose-volume parameters. The primary endpoint was a reduction in cardiac V5. RESULTS Median follow-up was 20 months (range, 2-31 months). For all patients, the PT plan better met the dosimetric goals and was used for treatment. Proton therapy alone was used for 10 patients (9 postmastectomy, 1 after BCT) and combined proton-photon in 8 (6 BCT, 2 postmastectomy with immediate expander reconstruction). Proton therapy improved coverage of level 2 axilla (P=.0005). Adequate coverage of internal mammary nodes was consistently achieved with PT (median D95, 50.3 Gy; range, 46.6-52.1 Gy) but not with conventional radiation therapy (median D95, 48.2 Gy; range, 40.8-55 Gy; P=.0005). Median cardiac V5 was 0.6% with PT and 16.3% with conventional radiation (P<.0001). Median ipsilateral lung V5 and V20 were improved with PT (median V5 35.3% vs 60.5% [P<.0001]; and median V20, 21.6% vs 35.5% [P<.0001]). Grade 3 dermatitis developed in 4 patients (22%), which was the only grade 3 toxicity. No grade 4+ toxicities developed. CONCLUSION Proton therapy for RNI after mastectomy or BCT significantly improves cardiac dose, especially for left-sided patients, and lung V5 and V20 in all patients without excessive acute toxicity. Proton therapy simultaneously improves target coverage for the internal mammary nodes and level 2 axilla, which may positively impact long-term survival in breast cancer patients.

Can proton therapy improve the therapeutic ratio in breast cancer patients at risk for nodal disease

Objectives:Regional node irradiation in patients with invasive breast cancer often results in increased radiation exposure to organs at risk. We evaluated the potential advantages of 3-dimensional conformal photon+proton therapy (3DCX+PT) in treating regional nodes versus photon-electron (3DCRT) or intensity-modulated radiotherapy (IMRT). Materials and Methods:Ten left-sided breast cancer patients underwent radiation treatment planning. 3DCX+PT, 3DCRT, and IMRT plans were generated for each patient. Results:There was no significant difference in target coverage between 3DCX+PT and IMRT. However, coverage of level II axillary lymph nodes was inferior with 3DCRT with a median D95 of 45 versus 50 Gy with either IMRT (P=0.0006) or 49.5 CGE with 3DCX+PT (P=0.0033). Internal mammary nodes coverage was also inferior with 3DCRT (median D95 was 42 Gy) compared with 47 Gy with IMRT (P=0.043) or 48.5 CGE with 3DCX+PT (P=0.0068).With 3DCX+PT, left lung V20 and V5 were 31% and 50% versus 36% (P=0.0368) and 70% (P=0.0007) with 3DCRT and 30% (P=0.7328) and 81% (P=0.0002) for IMRT. 3DCX+PT resulted in heart V20 and heart V5 of 0% and 7%, respectively, versus 4% (P=0.0067) and 24% (P=0.0002) with 3DCRT and 21% (P=0.0001), 50% (P=0.0001) with IMRT. The IMRT plans produced significantly higher integral, contralateral lung, and breast doses. Conclusions:Regional node target coverage was inferior with 3DCRT compared with either IMRT or 3DCX+PT. Organs at risk were exposed to less radiation with 3DCX+PT compared with 3DCRT or IMRT. Proton treatment offered both improved coverage of the regional lymph nodes and decreased dose to the heart, lung, and contralateral normal tissue.

Protons offer reduced bone marrow, small bowel, and urinary bladder exposure for patients receiving neoadjuvant radiotherapy for resectable rectal cancer

BACKGROUND To assess the potential benefit of proton therapy (PT) over photon therapy, we compared 3-dimensional conformal radiotherapy (3DCRT), intensity-modulated radiotherapy (IMRT), and PT plans in patients undergoing neoadjuvant chemoradiation for resectable rectal cancer at our institution. METHODS Eight consecutive patients with resectable (T2-T3) rectal cancers underwent 3DCRT, IMRT, and 3-dimensional conformal PT treatment planning. Initial target volumes (PTV1) were contoured using the Radiation Therapy Oncology Group anorectal atlas guidelines. Boost target volumes (PTV2) consisted of the gross rectal tumor plus a uniform 2-cm expansion. Plans delivered 45 Gray (Gy) or Cobalt Gray Equivalent (CGE) to the PTV1 and a 5.4-Gy (CGE) boost to the PTV2. Ninety-five percent of the PTVs received 100% of the target dose and 100% of the PTVs received 95% of the target dose. Standard normal-tissue constraints were utilized. Wilcoxon paired t-tests were performed to compare various dosimetric points between the 3 plans for each patient. RESULTS All plans met all normal-tissue constraints and were isoeffective in terms of PTV coverage. The proton plans offered significantly reduced median normal-tissue exposure over the 3DCRT and IMRT plans with respect to pelvic bone marrow at the V5Gy, V10Gy, V15Gy, and V20Gy levels and the small bowel space at the V10Gy and V20Gy levels. The proton plans also offered significantly reduced median normal-tissue exposure over the 3DCRT plans with respect to the small bowel at the V30Gy and V40Gy levels and the urinary bladder at the V40Gy level. CONCLUSIONS By reducing bone marrow exposure, PT may reduce the acute hematologic toxicity of neoadjuvant chemoradiation and increase the likelihood of uninterrupted chemotherapy delivery. Bone marrow sparing may also facilitate the delivery of salvage chemotherapy for patients who subsequently develop hematogenous metastasis. Reduced small bowel exposure using PT may also reduce toxicity and possibly facilitate the use of more-aggressive chemotherapy with radiotherapy.

Proton Therapy and Concomitant Capecitabine for Non-Metastatic Unresectable Pancreatic Adenocarcinoma

Abstract Purpose: To review early outcomes for patients enrolled on our institutions protocol (PC01) for patients with unresectable pancreatic cancer, and to test whether the serious adverse event rate could be reduced from 15% (expected) to <5%. Patients and Methods: Twelve patients were enrolled, but only 11 patients are reported in this analysis. Pathology on all patients was reviewed at University of Florida Health Medical Center in Jacksonville to confirm the diagnosis of pancreatic adenocarcinoma. Unresectability was defined by radiographic evidence of encasement of the celiac axis and/or superior mesenteric artery or by occlusion of the superior mesenteric vein, portal vein, or both confluences. Patients received proton therapy to a planning target volume dose of 59.4 Gy (relative biological effective) at 1.8 Gy (relative biological effective) per fraction over 7 weeks with concomitant oral capecitabine (1000 mg orally twice-daily, 5 days/week on radiation treatment days only). Only gross disease ...

Proton‐based chemoradiation for synchronous bilateral non‐small‐cell lung cancers: A case report

In this case report, we present the history and treatment of a 70‐year‐old man with synchronous bilateral non‐small‐cell lung cancers with proton‐beam radiation. Surgical treatment was not feasible and optimized photon intensity‐modulated radiotherapy (IMRT) to the primary tumors would have resulted in unacceptably high normal‐tissue exposures. Proton‐beam radiation enabled radiation dose escalation and concurrent chemotherapy while maintaining normal‐tissue tolerance.

A Technical Guide for Passive Scattering Proton Radiation Therapy for Breast Cancer

Most patients treated with proton therapy have had eye tumors, sarcomas, or, more recently, pediatric, or prostate cancers. As more proton centers have developed globally, increased capacity will permit exploration of other potential indications for proton therapy, including for the treatment of breast cancer. The rationale for proton therapy in the treatment of breast cancer is reduced inadvertent radiation dose to the heart and lung, as well as improved target coverage. As with any new technology, multiple technical parameters require optimization to deliver safe and effective radiation therapy and to maximize the benefits of the new technology. The purpose of this report is to provide a technical guide for the treatment of breast cancer with passive-scattering proton therapy and an algorithm for selecting patients with breast cancer who would benefit from proton therapy.

Two-year outcomes of a prospective study of proton therapy for breast cancer regional nodal irradiation.

65 Background: Through improved nodal coverage and decreased dose to the heart and lung, proton therapy (PT) may improve the therapeutic ratio for treatment of breast cancer requiring regional nodal irradiation (RNI). The purpose of this study is to report 2-year disease control and toxicity. METHODS From May 2012 to February 2014, 18 women (stage IIA-IIIB) were prospectively enrolled on a pilot study. Median age was 51.8 yrs (range, 42-73), with equal division between breast-conserving therapy (BCT) and mastectomy and right- and left-sided cancers. Median number of positive nodes among the 16 node-positive patients was 2 (range, 1-14). Five patients had ≥ 10 nodes positive on axillary dissection (N3a). Treatment targets (clinical target volumes for breast/chest wall, supraclavicular, axillary, internal mammary nodes) and organs at risk were delineated on CT scans. PT alone was used for 10 patients (9 postmastectomy; 1 postBCT) and combined proton-photon in 8 (all BCT). Toxicity was prospectively recorded using CTCAE v4.0. RESULTS Median follow-up was 1.9 yrs (range, 0.3 - 1.7). Two-year overall survival was 94% and locoregional control was 100%. Two-year distant metastases-free survival was 76%. No grade 4+ toxicity developed. Two patients developed grade 3 cellulitis. One patient had a reconstructive failure associated with postsurgical cellulitis. A right-sided patient was diagnosed with congestive heart failure 2 months after completing PT after diagnosis of a pulmonary embolus 1 month prior. She had elevated B-type natriuretic peptide before PT after adriamycin-based chemotherapy. Mean heart dose was 0 Gy and cardiac V5 0%. Grade 2 toxicities included pneumonitis in 1 patient who received concurrent chemotherapy, fatigue (n = 1), breast atrophy after removal of a 10x6x3cm lumpectomy cavity (n = 1), and lymphedema in 1 patient with > 20 nodes surgically excised. One patient with a history of rib fractures developed an ipsilateral rib fracture 7 months after PT. CONCLUSIONS For women with locally advanced breast cancer, PT for RNI has proven feasible after either mastectomy or BCT. PT allows for highly conformal radiation delivery without compromise of target coverage or excess exposure of normal tissue. CLINICAL TRIAL INFORMATION NCT01365845.

Proton therapy versus photon radiation therapy for the management of a recurrent desmoid tumor of the right flank: a case report

Desmoid tumors are benign mesenchymal tumors with a strong tendency for local recurrence after surgery. Radiotherapy improves local control following incomplete resection, but nearby organs at risk may limit the dose to the target volume. The patient in this report presented with a recurrent desmoid tumor of the right flank and underwent surgery with microscopically positive margins. Particular problems presented in this case included that the tumor bed was situated in close proximity to the liver and the right kidney and that the right kidney was responsible for 65% of the patient’s renal function. Intensity-modulated radiation therapy plans delivering 54 Gy necessarily exposed the right kidney to a V18 of 98% and the liver to a V30 of 55%. Proton therapy plans significantly reduced the right kidney V18 to 32% and the liver V30 to 28%. In light of this, the proton plan was utilized for treatment of this patient. Proton therapy was tolerated without gastrointestinal discomfort or other complaints. Twenty-four months after initiation of proton therapy, the patient is without clinical or radiographic evidence of disease recurrence. In this setting, the improved dose distribution associated with proton therapy allowed for curative treatment of a patient who arguably could not have been safely treated with intensity-modulated radiation therapy or other methods of conventional radiotherapy.

Abstract P1-15-20: Prospective study of proton radiotherapy for treatment of regional lymphatics in breast cancer

Purpose : To compare dosimetric endpoints between proton therapy (PT) and conventional radiation and to determine the feasibility of PT for regional nodal irradiation (RNI) in women with breast cancer. Methods : From May 2012 to February 2014, 18 women (stage IIA-IIIB) prospectively enrolled on a pilot study. Median age was 51.8 years (range, 42-73), with equal division between breast-conserving therapy (BCT) and mastectomy and right and left-sided cancers. Treatment targets (CTVs for breast/chest wall, supraclavicular, axillary, internal mammary nodes [IMNs]) and organs at risk were delineated on CT scans, and PT and conventional plans were developed. PT alone was used for 10 patients (9 post-mastectomy, 1 after BCT) and combined proton-photon in 8 (all BCT). Acute toxicity was prospectively recorded using CTCAE v4.0. A Wilcoxon signed-rank sum test compared the dose-volume parameters. Results : Median followup was 10.6 months (range, 1.1-19.1). For all patients, the PT plan better met the dosimetric goals and was used for treatment. Breast/chest wall coverage was adequate (V47.5=96.6% for both plans). PT improved coverage of level II axilla (median D95, 48.9Gy [range, 44.8-51.4Gy] with PT vs 45.4Gy [range, 39.8-51Gy] with conventional; p=0.0005). Adequate coverage of IMNs was consistently achieved with PT (median D95, 48.9Gy with a range of 44.8-51.4Gy) but not with conventional (median D95, 45.4Gy with range of 39.8-51Gy; p=0.0005); PT reduced heart dose in all patients. Median ipsilateral lung V5 measured 35.3% for PT compared to 60.5% for conventional (p Grade 3 dermatitis developed in 4 patients (22%), which was the only grade 3 toxicity. All patients developed grade 2 dermatitis; other acute grade 2 toxicities included fatigue (n= 6) and esophagitis (n=5). No grade 4+ toxicities developed. Dermatitis resolved by 1 month after PT for all but 1 patient who developed cellulitis (grade 2). Conclusion : PT for RNI after mastectomy or BCT significantly improves cardiac dose especially for left-sided patients and lung V5 and V20 in all patients without excessive acute toxicity. PT simultaneously improves target coverage for the IMN and level II axilla, which may positively impact long-term survival in breast cancer patients. Citation Format: Julie A Bradley, Roi Dagan, Meng Wei Ho, Christopher G Morris, Zuofeng Li, Nancy P Mendenhall. Prospective study of proton radiotherapy for treatment of regional lymphatics in breast cancer [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P1-15-20.