Noninferiority of Hypofractionated vs Conventional Postprostatectomy Radiotherapy for Genitourinary and Gastrointestinal Symptoms: The NRG-GU003 Phase 3 Randomized Clinical Trial.

Importance: No prior trial has compared hypofractionated postprostatectomy radiotherapy (HYPORT) to conventionally fractionated postprostatectomy (COPORT) in patients primarily treated with prostatectomy. Objective: To determine if HYPORT is noninferior to COPORT for patient-reported genitourinary (GU) and gastrointestinal (GI) symptoms at 2 years. Design, Setting, and Participants: In this phase 3 randomized clinical trial, patients with a detectable prostate-specific antigen (PSA; ≥0.1 ng/mL) postprostatectomy with pT2/3pNX/0 disease or an undetectable PSA (<0.1 ng/mL) with either pT3 disease or pT2 disease with a positive surgical margin were recruited from 93 academic, community-based, and tertiary medical sites in the US and Canada. Between June 2017 and July 2018, a total of 296 patients were randomized. Data were analyzed in December 2020, with additional analyses occurring after as needed. Intervention: Patients were randomized to receive 62.5 Gy in 25 fractions (HYPORT) or 66.6 Gy in 37 fractions (COPORT). Main Outcomes and Measures: The coprimary end points were the 2-year change in score from baseline for the bowel and urinary domains of the Expanded Prostate Cancer Composite Index questionnaire. Secondary objectives were to compare between arms freedom from biochemical failure, time to progression, local failure, regional failure, salvage therapy, distant metastasis, prostate cancer-specific survival, overall survival, and adverse events. Results: Of the 296 patients randomized (median [range] age, 65 [44-81] years; 100% male), 144 received HYPORT and 152 received COPORT. At the end of RT, the mean GU change scores among those in the HYPORT and COPORT arms were neither clinically significant nor different in statistical significance and remained so at 6 and 12 months. The mean (SD) GI change scores for HYPORT and COPORT were both clinically significant and different in statistical significance at the end of RT (-15.52 [18.43] and -7.06 [12.78], respectively; P < .001). However, the clinically and statistically significant differences in HYPORT and COPORT mean GI change scores were resolved at 6 and 12 months. The 24-month differences in mean GU and GI change scores for HYPORT were noninferior to COPORT using noninferiority margins of -5 and -6, respectively, rejecting the null hypothesis of inferiority (mean [SD] GU score: HYPORT, -5.01 [15.10] and COPORT, -4.07 [14.67]; P = .005; mean [SD] GI score: HYPORT, -4.17 [10.97] and COPORT, -1.41 [8.32]; P = .02). With a median follow-up for censored patients of 2.1 years, there was no difference between HYPORT vs COPORT for biochemical failure, defined as a PSA of 0.4 ng/mL or higher and rising (2-year rate, 12% vs 8%; P = .28). Conclusions and Relevance: In this randomized clinical trial, HYPORT was associated with greater patient-reported GI toxic effects compared with COPORT at the completion of RT, but both groups recovered to baseline levels within 6 months. At 2 years, HYPORT was noninferior to COPORT in terms of patient-reported GU or GI toxic effects. HYPORT is a new acceptable practice standard for patients receiving postprostatectomy radiotherapy. Trial Registration: ClinicalTrials.gov Identifier: NCT03274687.

Role of molecular signature to differentiate second primary lung cancer from metastasis in a patient with squamous cell carcinoma of oral cavity.

BACKGROUND: Lung is the most common site of distant metastasis for patients with head and neck squamous cell carcinoma (HNSCC). However, differentiating second primary lung cancers from metastasis may be difficult for p16 negative HNSCC. CASE: We describe a case of oral cavity squamous cell carcinoma (SCC) who was found to have lung nodule and hilar lymphadenopathy (LAD) after surgery and radiation therapy. Hilar node was consistent with SCC however, it was difficult to differentiate second primary lung cancer and metastasis from oral cavity SCC. Next-generation sequencing was done for the primary oral cavity and the hilar node. Both samples had the same type of TP53 mutation and variants of unknown significance suggesting metastatic HNSCC. He was treated with a chemotherapy regimen for metastatic HNSCC. CONCLUSION: Molecular studies can help to differentiate metastasis from second primary lung cancers for p16 negative HNSCC.

High postprostatectomy prostate-specific antigen level prior to salvage radiation therapy is not always a bad sign.

Although radical prostatectomy is a popular treatment modality for clinically localized prostate cancer, 10-year biochemical recurrence can reach 28%. Before salvage radiation therapy (SRT), prostate-specific antigen (PSA) values alone should be used cautiously in predicting SRT eligibility. A long, slow PSA rise may suggest locally confined disease still amenable to SRT; corresponding imaging to identify potential gross recurrence is useful. Patients with local disease may safely benefit from higher doses of radiation.

Early breast cancer with positive margins: excellent local control with an upfront brachytherapy boost.

Standard breast conservation therapy consists of lumpectomy and whole breast radiation with boost. The effectiveness of radiation in cases of positive margins is controversial. Two potential treatment-related factors are time to initiation of radiation and localization of the boost. Here, we examine long-term outcomes of positive margin cases treated with an upfront interstitial brachytherapy boost. This particular treatment arrangement may reduce those treatment-related effects on local control. Historically, a low dose interstitial implant was a common boost technique. One approach administered the boost before external beam. A review of 521 cases treated at our institution was conducted. Patients were selected for this study if they received an upfront brachytherapy boost and had close or positive margins. Forty-four breast cancers were identified. Median follow-up of survivors was 11.3 years (8.1-21.7). Implant was performed at lumpectomy (12) or axillary dissection (32). Margin statuses were: focal carcinoma at ink (37), multifocal carcinoma at ink (1), carcinoma <1 mm from ink (2), and DCIS at ink (4). Median tumor size was 1.2 cm (0.5-3.5 cm). Ten patients had nodal involvement. Total median dose was 60 Gy (58.6-65.3 Gy). Median boost dose was 15 Gy (12-20.3 Gy). Lumpectomy to boost interval was median of 3 weeks (0-10.8). No ipsilateral breast recurrences or second primaries were identified. Four developed contralateral breast cancer. Eleven are deceased, four from breast cancer-all from metastasis. 12-year Kaplan-Meier estimates were: overall survival 78 ± 7 %, cause specific survival 93 ± 4 %, and recurrence-free survival 82 ± 6 %. Univariate analysis identified nodal disease as significant for cause specific survival (log rank p = 0.005). No ipsilateral breast recurrences were found. Early administered radiation and accurate boost localization were identified as suspected treatment-related factors for local recurrence. When these two treatment-related factors are minimized, long-term local control rates do not suffer.

Relationship of protein and calorie intake to the severity of oral mucositis in patients with head and neck cancer receiving radiation therapy.

BACKGROUND: The purpose of this study was to evaluate the relationship of calorie and protein intake to the severity of oral mucositis in patients with head and neck cancer receiving radiation therapy. METHODS: Patients with head and neck cancer undergoing ≥60 Gy of radiation were eligible. Weekly data were collected for oral mucositis grade and protein and calorie intake. Proportional odds models examined the association of oral mucositis severity with nutritional predictors. RESULTS: During a 24-month period, 40 evaluable patients met criteria for inclusion. In a multivariate backward selection model, the sole significant nutritional predictor of reduced oral mucositis severity was meeting the protein goal for the current week (p = .01; adjusted odds ratio [OR], 2.30). CONCLUSION: Patients who met protein-related goals during radiotherapy for head and neck cancer had less severe oral mucositis. Nutritional counseling during radiotherapy, with emphasis on protein goals, may reduce oral mucositis severity.

Intensity-modulated radiation therapy in childhood ependymoma.

PURPOSE: To determine the patterns of failure after intensity-modulated radiation therapy (IMRT) for localized intracranial ependymoma. METHODS AND MATERIALS: From 1994 to 2005, 22 children with pathologically proven, localized, intracranial ependymoma were treated with adjuvant IMRT. Of the patients, 12 (55%) had an infratentorial tumor and 14 (64%) had anaplastic histology. Five patients had a subtotal resection (STR), as evidenced by postoperative magnetic resonance imaging. The clinical target volume encompassed the tumor bed and any residual disease plus margin (median dose 54 Gy). Median follow-up for surviving patients was 39.8 months. RESULTS: The 3-year overall survival rate was 87% +/- 9%. The 3-year local control rate was 68% +/- 12%. There were six local recurrences, all in the high-dose region of the treatment field. Median time to recurrence was 21.7 months. Of the 5 STR patients, 4 experienced recurrence and 3 died. Patients with a gross total resection had significantly better local control (p = 0.024) and overall survival (p = 0.008) than those with an STR. At last follow-up, no patient had developed visual loss, brain necrosis, myelitis, or a second malignancy. CONCLUSIONS: Treatment with IMRT provides local control and survival rates comparable with those in historic publications using larger treatment volumes. All failures were within the high-dose region, suggesting that IMRT does not diminish local control. The degree of surgical resection was shown to be significant for local control and survival.

Supine craniospinal irradiation using intrafractional junction shifts and field-in-field dose shaping: early experience at Methodist Hospital.

PURPOSE: To describe our preliminary experience with supine craniospinal irradiation. The advantages of the supine position for craniospinal irradiation include patient comfort, easier access to maintain an airway for anesthesia, and reduced variability of the head tilt in the face mask. METHODS AND MATERIALS: The cranial fields were treated with near lateral fields and a table angle to match their divergence to the superior edge of the spinal field. The collimator was rotated to match the divergence from the superior spinal field. The spinal fields were treated using a source to surface distance (SSD) technique with the couch top at 100 cm. When a second spinal field was required, the table and collimator were rotated 90 degrees to allow for the use of the multileaf collimator and so the gantry could be rotated to match the divergence of the superior spinal field. The multileaf collimator was used for daily dynamic featherings and field-in-field dose control. RESULTS: With a median follow-up of 20.2 months, five documented failures and no cases of radiation myelitis occurred in 23 consecutive patients. No failures occurred in the junctions of the spine-spine or brain-spine fields. Two failures occurred in the primary site alone, two in the spinal axis alone, and one primary site failure plus distant metastasis. The median time to recurrence was 17 months. CONCLUSION: The results of our study have shown that supine approach for delivering craniospinal irradiation is not associated with increased relapses at the field junctions. To date, no cases of radiation myelitis have developed.