External Beam Proton Therapy Research Articles

High-Dose-Rate Brachytherapy for Vaginal Rhabdomyosarcoma (RMS): Lessons Learned at a Single Institution

Botryoid RMS is a rare pediatric tumor most commonly arising within the vaginal wall of girls under age three. Most patients are successfully treated with low-risk chemotherapy protocols but local treatment is required to minimize risk of local relapse. Intravaginal brachytherapy is an effective local therapy that can minimize sequelae in these very young patients. We reviewed records of all patients with RMS who received intravaginal high-dose-rate brachytherapy from 2010-2022 at a single institution. All were treated with multiagent chemotherapy with or without minor surgical procedures, and had no gross disease prior to intravaginal brachytherapy. All patients underwent CT simulation under anesthesia and optimal-sized cylindrical applicators were chosen based on patient anatomy. Twelve girls, median age 23 months (range 3-33), were treated with daily anesthesia. All were Stage 1 and 92% had Group III disease. A single patient had Group IIA disease based on up-front resection. Early in the series, 5 patients received 21 Gy in 7 fractions according to COG protocol guidelines. Subsequent patients received higher doses of 28-30 Gy in 7-10 fractions. Custom sized cylinders were used with diameters ranging from 1.2-1.6 cm and dose was prescribed to a median depth of 3 mm. Median mean dose to the rectum, bladder, uterus, and bilateral ovaries was 8.7 Gy, 7.2 Gy, 6.9 Gy, and 5.0 Gy, respectively. Median follow-up was 4 years (range 1-10). No acute or late side effects have occurred. At follow-up, three girls were of pubescent age, all three exhibited signs of puberty and two had reached menarche. Three girls (25%) suffered local relapse at a median of 15 months (range 5-16 months) after brachytherapy. One-year and five-year local control rates were 92% (95% CI 54-99%) and 70% (95% CI 32-89%), respectively. All relapses were in patients receiving 21 Gy and two were beyond full dose coverage of brachytherapy at the introitus and in the uterus. Subsequent patients receiving higher doses and full coverage of the vagina have had no local failures. Two of three patients who failed were cured with salvage therapy resulting in one-year and five-year overall survival rates of 100% and 86% (95% CI 33-98%), respectively. Intravaginal high-dose-rate brachytherapy is an excellent option for local control of vaginal RMS with fewer long-term risks than external beam proton therapy or radical surgery. A dose of 28 Gy in 7 fractions prescribed to the entire vagina is necessary for optimal prevention of relapse. Longer follow-up is needed to confirm preservation of ovarian, reproductive, and sexual function.

Current treatment of pediatric bladder and prostate rhabdomyosarcoma (bladder preserving vs. radical cystectomy).

To discuss alternative strategies for multimodal treatments of nonmetastatic bladder-prostate rhabdomyosarcoma performed with the aim of preserving organ function. Bladder-prostate rhabdomyosarcomas are seldom fully resectable at presentation or after induction chemotherapy, and extensive resection might not improve survival. When an organ-sparing approach is pursued, radiotherapy might be unavoidable to achieve reliable local control of the disease. Benefits of preoperative vs. postoperative radiotherapy have yet to be investigated. Multimodal treatments may often result in bladder function impairment and erectile dysfunction. To reduce long-term side effects of radiotherapy, irradiation modalities allowing for more targeted treatment should be favoured. For this purpose, external beam proton therapy or nonradical surgery associated with brachytherapy may be viable options. Nevertheless, experience with these treatments is still limited. Advancements in lower urinary tract reconstruction make preservation of volitional voiding and erectile function possible after cystoprostatectomy. But in the context of multimodal treatment, cystoprostatectomy is reserved to patients who respond poorly to other treatments. For the vast majority of bladder-prostate rhabdomyosarcoma, we believe that reliable local control of disease can only be achieved with the use of radiotherapy. Efforts should be made to find the best modality for targeted radiotherapy. Further studies are required to compare preoperative vs. postoperative radiotherapy and the best dose to be administered in order to reduce long-term side effects. If creation of an orthotopic continent diversion is deemed appropriate in patients undergoing cystoprostatectomy, it should be performed concurrently with extirpative surgery.

UVEAL MELANOMAS: Conservation Treatment

Eye conservation can be achieved in patients with uveal melanomas by several techniques, with external beam charged particle (proton) therapy and episcleral radionuclide plaque therapy being used most commonly. The probability of visual preservation and of eye retention with either technique is related to tumor size and location. If vision is poor or absent in the fellow eye, even very large tumors can be treated with the proton beam, with a 75% to 80% probability of eye salvage and preservation of some degree of visual function. Local control is achieved in a large proportion of treated eyes with either technique probably because of the large doses that can be focally administered to these relatively small tumors with those techniques. Achieving local control may also contribute to improved survival in some patients. Survival clearly has not been compromised. Useful vision is preserved in eyes with tumors occurring in a favorable location with respect to the optic disc or macula. A dose-searching trial, aimed at improving visual outcome in patients with tumors in unfavorable locations, has been completed and has provided data to aid in designing future trials. Successfully treating uveal melanoma without removal of the involved eye is one of the major oncologic triumphs of the latter part of the 20th century. Very high rates of local control can be achieved with heavy charged particle external beam radiotherapy or 125I episcleral plaque brachytherapy, with preservation of a functionally useful eye in many patients. The excellent results in the eye melanoma patients treated with external beam proton therapy also demonstrate that almost all the patients can successfully cooperate in their treatment by voluntarily fixating the eye on a particular point during treatment, so that their tumor is positioned properly in the beam during treatment. Conservative treatment can achieve local control rates similar to or superior to those achieved with radiation therapy alone in other commonly treated solid tumors, including early stage carcinomas of the breast, vocal cord, and prostate. Continued careful follow-up of conservatively treated patients will provide even better understanding of the radiation effects on uveal melanomas and on normal ocular structures. It is also impressive that these gains have not been achieved at a cost of increased mortality: survival rates in irradiated patients are at least as good as after enucleation. Further observation will reveal whether these initial dramatic and encouraging results will be maintained. The COMS Study may provide additional data in this regard at least regarding survival after brachytherapy relative to enucleation. It will not, however, clarify indications for the two types of radiotherapy (brachytherapy and charged particle therapy) nor will it allow direct comparisons of acute and chronic ocular effects of those therapeutic modalities. The UCSF-LBL trial mentioned previously, which compared helium ion therapy with 125I episcleral plaque treatment, has documented the superiority of charged particle therapy to plaque therapy in terms of local tumor control and eye retention. Of interest is a recent survey reporting that choice of treatment for uveal melanoma did not seem to be associated with large differences in quality of life when assessed at long-term follow-up. The distant failures and metastatic deaths in uveal melanoma patients, more common with larger and more anteriorly located tumors, are most distressing. A randomized clinical trial of adjuvant systemic therapy is clearly indicated but has not been mounted because of the relatively poor results obtained with systemic therapy in metastatic melanoma patients. The recent report of improved survival in cutaneous melanoma patients at high risk for metastasis who were treated with interferon is encouraging, and it led to the initiation of the nonrandomized study described previously, which uses interferon following proton eye irradiation for patients with increased risk of metastasis. Other trials would clearly be indicated if more effective systemic therapies become available.