Experience with intraoperative radiation therapy in an urban cancer center.

BACKGROUND/OBJECTIVE: Intra-operative radiation therapy (IORT) is a newer partial breast irradiation technique that has been well studied in 2 large randomized trials, the TARGIT-A and ELIOT trials. We initiated our IORT program in 2018 in the context of a registry trial, and aim to report our early results thus far. METHODS: We instituted an IORT practice using Intrabeam® low energy 50kVp x-rays for selected breast cancer cases in 2018. Patients were enrolled on our institutional registry protocol which allowed for IORT in ER + patients with grade 1-2 DCIS ≤ 2.5 cm or invasive disease ≤ 3.5 cm in patients of at least 45 years of age. RESULTS: Between January 2018 and December 2021, 181 patients with clinical stage 0-IIA ER + breast cancer were evaluated. One hundred sixty-seven patients ultimately received IORT to 172 sites. The majority of patients received IORT at the time of initial diagnosis and surgery (160/167; 95.8%). Re-excision post IORT occurred in 16/167 patients (9.6%) due to positive margins. Adjuvant RT to the whole breast +/- LN was ultimately given to 23/167 (13.8%) patients mainly due to positive sentinel LN found on final pathology (12/23; 52%); other reasons were close margins for DCIS (3/23; 13%), tumor size (3/23; 4.3%), and multifactorial (5/23; 17.4%). Five patients (3%) had post-operative complications of wound dehiscence. There were 3 local recurrences (1.6%) at a median follow-up of 27.9 months (range: 0.7- 54.8 months). CONCLUSIONS: IORT has been proven to be a safe and patient-centered form of local adjuvant RT for our population, in whom compliance with a longer course of external beam radiation can be an issue. Long term efficacy remains to be evaluated through continued follow up. In the era of COVID-19 and beyond, IORT has been an increasingly attractive option, as it greatly minimizes toxicities and patient visits to the clinic. TRIAL REGISTRATION: All patients were prospectively enrolled on an institutional review board-approved registry trial (IRB number: 2018-9409).

Prolongation of radiotherapy duration is associated with inferior overall survival in patients with pediatric medulloblastoma and central nervous system primitive neuroectodermal tumors.

BACKGROUND: The importance of radiotherapy (RT) duration in medulloblastoma in the modern era of chemotherapy has not been well elucidated. The aim of this study was to determine the impact of RT treatment duration on overall survival (OS) in pediatric medulloblastoma and cenral nervous system neuroectodermal tumors (PNETs). METHODS: The National Cancer Database (NCDB) was queried to identify patients with newly diagnosed medulloblastoma and CNS PNETs diagnosed between 2004 and 2014. Patients were excluded if they had extraneural metastasis, did not receive standard craniospinal irradiation dose, had a nonstandard total dose outside of 54 or 55.8 Gy, did not receive adjuvant chemotherapy, or if the RT duration was outside of the expected range of 37 to 80 days. The Kaplan-Meier estimator was used to estimate the association between RT duration (≤45 days or >45 days) and OS. Multivariate Cox regression was used to assess other confounders of OS. RESULTS: Six-hundred twenty-five patients met inclusion criteria, of which 181 were assigned to the "RT long" (>45 days) cohort (29.0%) and 444 (71.0%) to the "RT short" group (≤45 days). The five-year OS for the "RT short" compared with "RT long" cohort was 82.2% versus 70.9%, respectively (log-rank, P < 0.0037). For average risk patients, the five-year OS was 84.6% versus 86.4% for "RT short" and "RT long," respectively (log-rank, P = 0.40). However, for high-risk patients, five-year OS was 77.7% versus 51.0% (log-rank, P < 0.0001) in the "RT short" and "RT long" cohorts. CONCLUSION: For patients with high-risk medulloblastoma and CNS PNETs, RT duration >45 days was associated with inferior OS.

A skin dose prediction model based on in vivo dosimetry and ultrasound skin bridge measurements during intraoperative breast radiation therapy.

PURPOSE: Using in vivo measurements from optically stimulated luminescence dosimeters (OSLDs) to develop and validate a prediction model for estimating the skin dose received by patients undergoing breast intraoperative radiation therapy (IORT). METHODS AND MATERIALS: IORT was performed using INTRABEAM-600 with spherical applicators placed in the lumpectomy cavity. Ultrasound skin bridge measurements were used to determine the applicator-to-skin distance, with OSLDs placed to measure the skin surface dose at the corresponding points. The OSLD response was calibrated for the 50 kVp INTRABEAM-600 output. Models were fit to describe the dose fall-off with increasing applicator-to-skin distance and the best fitting model was chosen for estimating skin dose. RESULTS: Twenty four patients with 25 lumpectomy cavities were included, and the average skin dose recorded was 1.18 Gy ± 0.88 Gy, ranging from 0.17 Gy to 4.77 Gy, with an average applicator-to-skin distance of 19.9 mm ± 5.1 mm. An exponential-plateau model was found to best describe the dose fall-off with a root-mean-square error of 0.73. This model was then validated prospectively using skin dose measurements from five consecutive patients. Validation measurements were well within the 95% prediction limits of the model, with a root-mean-square error of 0.52, showing that the prediction model accurately estimates skin dose using ultrasound skin bridge measurements. CONCLUSIONS: This prediction model constitutes a useful tool for estimating the skin dose received during breast lumpectomy IORT. The model and accompanying 95% confidence intervals can be used to establish a minimum allowable skin bridge distance, effectively limiting the maximum allowable skin dose.

Neoadjuvant radiation therapy for the management of myoepithelial carcinoma of the upper extremity.

Myoepithelial tumors of the soft tissue are a rare tumor displaying myoepithelial elements and lacking obvious ductal differentiation. The rarity of these precludes any evidence-based consensus regarding optimal management. Nevertheless, the current approach to these lesions begins with amputation or complete excision. The efficacy of neoadjuvant or adjuvant radiation therapy or chemotherapy has not been established. Here, we present the first report to the authors' knowledge of neoadjuvant radiation therapy for the treatment of this rare soft tissue neoplasm and review the management and outcomes of published cases of myoepithelial carcinoma. A patient with a soft tissue myoepithelial carcinoma that declined both amputation and chemotherapy was treated with neoadjuvant radiation therapy and wide surgical excision followed by a brachytherapy boost to the resected tumor bed. Neoadjuvant radiation therapy resulted in an excellent response with extensive treatment-related changes consisting predominantly of fibrosis, hyalinization and hemorrhage and only 10% residual viable myoepithelial carcinoma present in the surgical specimen.

Proton Beam Reirradiation for Recurrent Head and Neck Cancer: Multi-institutional Report on Feasibility and Early Outcomes.

PURPOSE: Reirradiation therapy (re-RT) is the only potentially curative treatment option for patients with locally recurrent head and neck cancer (HNC). Given the significant morbidity with head and neck re-RT, interest in proton beam radiation therapy (PBRT) has increased. We report the first multi-institutional clinical experience using curative-intent PBRT for re-RT in recurrent HNC. METHODS AND MATERIALS: A retrospective analysis of ongoing prospective data registries from 2 hybrid community practice and academic proton centers was conducted. Patients with recurrent HNC who underwent at least 1 prior course of definitive-intent external beam radiation therapy (RT) were included. Acute and late toxicities were assessed with the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 and the Radiation Therapy Oncology Group late radiation morbidity scoring system, respectively. The cumulative incidence of locoregional failure was calculated with death as a competing risk. The actuarial 12-month freedom-from-distant metastasis and overall survival rates were calculated with the Kaplan-Meier method. RESULTS: Ninety-two consecutive patients were treated with curative-intent re-RT with PBRT between 2011 and 2014. Median follow-up among surviving patients was 13.3 months and among all patients was 10.4 months. The median time between last RT and PBRT was 34.4 months. There were 76 patients with 1 prior RT course and 16 with 2 or more courses. The median PBRT dose was 60.6 Gy (relative biological effectiveness, [RBE]). Eighty-five percent of patients underwent prior HNC RT for an oropharynx primary, and 39% underwent salvage surgery before re-RT. The cumulative incidence of locoregional failure at 12 months, with death as a competing risk, was 25.1%. The actuarial 12-month freedom-from-distant metastasis and overall survival rates were 84.0% and 65.2%, respectively. Acute toxicities of grade 3 or greater included mucositis (9.9%), dysphagia (9.1%), esophagitis (9.1%), and dermatitis (3.3%). There was 1 death during PBRT due to disease progression. Grade 3 or greater late skin and dysphagia toxicities were noted in 6 patients (8.7%) and 4 patients (7.1%), respectively. Two patients had grade 5 toxicity due to treatment-related bleeding. CONCLUSIONS: Proton beam re-RT of the head and neck can provide effective tumor control with acceptable acute and late toxicity profiles likely because of the decreased dose to the surrounding normal, albeit previously irradiated, tissue, although longer follow-up is needed to confirm these findings.

Respiratory motion changes of lung tumors over the course of radiation therapy based on respiration-correlated four-dimensional computed tomography scans.

PURPOSE: To determine whether lung tumor respiratory excursion at simulation is predictive of excursion during radiation and whether phase offsets between tumor and surrogate markers are constant throughout treatment. METHODS AND MATERIALS: Respiration-correlated CT scans and two rescans (using a Brilliance Big Bore spiral CT simulator; Philips, Inc.) were obtained from 20 patients at simulation. Gross tumor volume (GTV) was contoured on 10 phases of the respiratory cycle, and excursions were calculated. Diaphragm and xyphoid motion were quantified. Phase offsets, DeltaPhi, were calculated for patients with a GTV motion of >3 mm. Interfraction differences in excursions between simulation and rescans and magnitudes of variation in phase offset between fractions were evaluated. RESULTS: Mean GTV excursions at simulation in superior-inferior, anterior-posterior, and medial-lateral directions were 0.67, 0.29, and 0.21 cm, respectively. The magnitude of superior-inferior GTV excursion correlated with tumor location (upper vs. lower lobe, p = 0.011). GTV excursions between simulation and rescan 1 (p = 0.115) and between simulation and rescan 2 (p = 0.071) were stable. Fourteen patients were analyzed for variations in phase offsets. GTV-xyphoid phase offset changed significantly between simulation and rescan 1 (p = 0.007) and simulation and rescan 2 (p = 0.008), with mean DeltaPhi values of 13.2% (rescan 1) and 14.3% (rescan 2). Xyphoid-diaphragm offset changed between simulation and rescan 1 (p = 0.004) and between simulation and rescan 2 (p = 0.012), with mean DeltaPhi values of 14.5% (rescan 1) and 7.6% (rescan 2). CONCLUSIONS: Interfraction consistency in tumor excursion suggests tumor excursion at simulation may direct therapy. Significant variations in phase lag between GTV and other anatomic structures throughout treatment have important implications for techniques that rely on surrogate structures to predict tumor motion.

Results of a phase I dose-escalation study using three-dimensional conformal radiotherapy in the treatment of inoperable nonsmall cell lung carcinoma.

BACKGROUND: The objective of this study was to report the results of a Phase I dose-escalation study using three-dimensional conformal radiation therapy (3D-CRT) for the treatment of patients with nonsmall cell lung carcinoma (NSCLC). METHODS: Between 1991 and 2003, 104 patients were enrolled for 3D-CRT at Memorial Sloan-Kettering Cancer Center. The median patient age was 69 years. Twenty-eight percent of patients had Stage I-II NSCLC, 33% of patients had Stage IIIA NSCLC, 32% of patients had Stage IIIB NSCLC, and 6% of patients had recurrent NSCLC. Induction chemotherapy was received by 16% of patients. Radiation was delivered in daily fractions of 1.8 grays (Gy) for doses < or = 81.0 Gy and in daily fractions of 2.0 Gy for higher doses. Accrual at a dose level was complete when 10 patients received the intended dose without unacceptable acute morbidity. RESULTS: After an incident of fatal acute radiation pneumonitis at the starting dose of 70.2 Gy, the protocol was modified to limit normal tissue complication probabilities (NTCP) to < 25%. The dose was then escalated from 70.2 Gy, to 75.6 Gy, 81.0 Gy, and 84.0 Gy, with at least 10 patients treated at each dose level. Unacceptable pulmonary toxicity occurred at 90.0 Gy. Subsequently, another 10 patients were accrued at the 84.0 Gy level with acceptable toxicity. Thus, 84.0 Gy was the maximum tolerated dose (MTD). The crude late pulmonary toxicity rate was 7%, the 2-year local control rate was 52%, the disease-free survival rate was 33%, and the overall survival rate was 40%. The median survival was 21.1 months. Overall survival was improved significantly in patients who received > or = 80.0 Gy. CONCLUSIONS: The MTD of 3D-CRT for NSCLC with an NTCP constraint of 25% was 84.0 Gy in the current study. There was a suggestion of improved survival in patients who received 80.0 Gy.

Does registration of PET and planning CT images decrease interobserver and intraobserver variation in delineating tumor volumes for non-small-cell lung cancer?

PURPOSE: To compare tumor volume delineation using registered positron emission tomography (PET)/CT vs. side-by-side image sets. METHODS AND MATERIALS: A total of 19 patients with non-small-cell lung cancer had 18-fluorine-deoxyglucose (FDG)-PET scans registered with planning CT scans. The disease was Stage I-II in 26%, IIIA in 42%, and IIIB in 32%. Two radiation oncologists contoured 9 tumor volumes using registered images (registered) and 10 using separate FDG-PET images as a guide (nonregistered). A third physician, who had done the treatment planning for these patients a median of 40 months before using registered images, repeated all contours: 10 on registered images (registered/registered) and 9 without registration (registered/nonregistered). Each pair of volumes (A and B) was compared. Quantitative comparison used the concordance index, (A intersection B)/(A union or logical sum B). For qualitative analysis, pairs of volumes were projected onto digitally reconstructed radiographs. The differences were graded as insignificant, minor, moderate, or major. RESULTS: The median interobserver percentage of concordance among nonregistered pairs was 61% vs. 70% in the registered group (p <0.05). On qualitative analysis, in the nonregistered group, the differences were insignificant in 5, minor in 3, and moderate in 2 of 10. The differences in the registered group were insignificant in 7 and minor in 2 of 9. The median intraobserver percentage of concordance in the registered/nonregistered group was 58% vs. 71% in the registered/registered group (p = 0.10). On qualitative analysis, the intraobserver differences in the registered/nonregistered group were insignificant in 2, minor in 2, moderate in 0, and major in 5 of 9. In the registered/registered group, the differences were insignificant in 2, minor in 6, moderate in 2, and major in 0 of 10. CONCLUSION: Registration of FDG-PET and planning CT images results in greater consistency in tumor volume delineation.

A pilot trial of high-dose-rate intraoperative radiation therapy for malignant pleural mesothelioma.

PURPOSE: To report results of a phase II trial of high-dose-rate intra-operative radiation therapy (HDR-IORT) for malignant pleural mesothelioma (MPM). METHODS AND MATERIALS: Seven patients had extrapleural pneumonectomy with IORT (EPP/IORT) and 6 patients had pleurectomy/decortication with IORT (PD/IORT) between 1994 and 1996. IORT was delivered with 192Ir using a customized applicator with a remote afterloader. A median of 3 sites were treated to a median area of 143 cm2. A dose of 1500 cGy was prescribed at each site, with 1000 cGy delivered to the mediastinum. Postoperative external beam radiation therapy (EBRT) was given 3-5 weeks later. Median follow-up was 8 months (range, 1-84 months). RESULTS: Five patients developed local failure. Two-year local control and survival rates were 35% and 23%, respectively. Mortality was 2/13 (15%), 1 from each surgical group. Serious complications requiring further intervention occurred in 3/6 (50%) of the EPP/IORT group and 1/5 (20%) of the PD/IORT group. CONCLUSIONS: HDR-IORT after EPP for MPM is prohibitively toxic and has been abandoned, while its use with PD remains in question.

Improved local control with higher doses of radiation in large-volume stage III non-small-cell lung cancer.

PURPOSE: It has been suggested that larger tumor volume is associated with poor survival in patients with non-small-cell lung cancer (NSCLC). We investigated whether high-dose radiation improved local control in patients with large-volume Stage III NSCLC. METHODS AND MATERIALS: Seventy-two patients with Stage III NSCLC and gross tumor volumes (GTV) of greater than 100 cc were treated with three-dimensional conformal radiotherapy (3D-CRT). Patients were divided into two groups: those treated to less than 64 Gy (37 patients) and those treated to 64 Gy or higher (35 patients). RESULTS: The 1-year and 2-year local failure rates were 27% and 47%, respectively, for Stage III patients treated to 64 Gy or higher, and 61% and 76%, respectively, for those treated to less than 64 Gy (p = 0.024). The median survival time for patients treated to 64 Gy or higher was 20 months vs. 15 months for those treated to less than 64 Gy (p = 0.068). Multivariate analysis revealed that dose and GTV are predictors of local failure-free survival. A 10 Gy increase in dose resulted in a 36.4% decreased risk of local failure. CONCLUSIONS: Our data suggest that administration of higher doses using 3D-CRT improves local control in Stage III NSCLC patients with large GTVs.

The effect of smoking status on survival following radiation therapy for non-small cell lung cancer.

The dangers of cigarette smoking are numerous and well-known, including the causal relationship to lung cancer. This study investigates the effect that smoking status at initial consultation has on radiation therapy for non-small cell lung cancer (NSCLC). We identified 237 patients treated between 1991 and 2001 with definitive radiation or chemoradiation who had complete smoking histories. Median age was 73, with 56% males. Distribution by stage was as follows: I/II-27%, IIIA-27%, IIIB-45%, recurrent-1%. Two-year overall survival, stratified by stage of disease, was calculated from the time of initiation of treatment. Median follow-up time from the end of treatment was 13 months. Among those with stage I/II disease, current smokers had a 2-year survival rate of 41% and a median survival of 13.7 months while non-smokers had a 2-year survival of 56% and a median survival of 27.9 months (P = 0.01). Patients with stage III disease did not show any significant differences in overall survival. There were no significant differences in cancer-specific survival in either stage. In conclusion, among NSCLC patients diagnosed with early stage disease, current smokers have a poorer prognosis for survival after radiation therapy.