Radiotherapy Plus Cisplatin With or Without Lapatinib for Non-Human Papillomavirus Head and Neck Carcinoma: A Phase 2 Randomized Clinical Trial.

Importance: Patients with locally advanced non-human papillomavirus (HPV) head and neck cancer (HNC) carry an unfavorable prognosis. Chemoradiotherapy (CRT) with cisplatin or anti-epidermal growth factor receptor (EGFR) antibody improves overall survival (OS) of patients with stage III to IV HNC, and preclinical data suggest that a small-molecule tyrosine kinase inhibitor dual EGFR and ERBB2 (formerly HER2 or HER2/neu) inhibitor may be more effective than anti-EGFR antibody therapy in HNC. Objective: To examine whether adding lapatinib, a dual EGFR and HER2 inhibitor, to radiation plus cisplatin for frontline therapy of stage III to IV non-HPV HNC improves progression-free survival (PFS). Design, Setting, and Participants: This multicenter, phase 2, double-blind, placebo-controlled randomized clinical trial enrolled 142 patients with stage III to IV carcinoma of the oropharynx (p16 negative), larynx, and hypopharynx with a Zubrod performance status of 0 to 1 who met predefined blood chemistry criteria from October 18, 2012, to April 18, 2017 (median follow-up, 4.1 years). Data analysis was performed from December 1, 2020, to December 4, 2020. Intervention: Patients were randomized (1:1) to 70 Gy (6 weeks) plus 2 cycles of cisplatin (every 3 weeks) plus either 1500 mg per day of lapatinib (CRT plus lapatinib) or placebo (CRT plus placebo). Main Outcomes and Measures: The primary end point was PFS, with 69 events required. Progression-free survival rates between arms for all randomized patients were compared by 1-sided log-rank test. Secondary end points included OS. Results: Of the 142 patients enrolled, 127 (median [IQR] age, 58 [53-63] years; 98 [77.2%] male) were randomized; 63 to CRT plus lapatinib and 64 to CRT plus placebo. Final analysis did not suggest improvement in PFS (hazard ratio, 0.91; 95% CI, 0.56-1.46; P = .34) or OS (hazard ratio, 1.06; 95% CI, 0.61-1.86; P = .58) with the addition of lapatinib. There were no significant differences in grade 3 to 4 acute adverse event rates (83.3% [95% CI, 73.9%-92.8%] with CRT plus lapatinib vs 79.7% [95% CI, 69.4%-89.9%] with CRT plus placebo; P = .64) or late adverse event rates (44.4% [95% CI, 30.2%-57.8%] with CRT plus lapatinib vs 40.8% [95% CI, 27.1%-54.6%] with CRT plus placebo; P = .84). Conclusion and Relevance: In this randomized clinical trial, dual EGFR-ERBB2 inhibition with lapatinib did not appear to enhance the benefit of CRT. Although the results of this trial indicate that accrual to a non-HPV HNC-specific trial is feasible, new strategies must be investigated to improve the outcome for this population with a poor prognosis. Trial Registration: ClinicalTrials.gov Identifier: NCT01711658.

A multi-institutional phase 2 trial of prostate stereotactic body radiation therapy (SBRT) using continuous real-time evaluation of prostate motion with patient-reported quality of life.

PURPOSE: The use of stereotactic body radiation therapy (SBRT) for prostate cancer has been reported predominantly from single institutional studies, although concerns for broader adoption exist. METHODS AND MATERIALS: From 2011 through 2013, 66 men were accrued to a phase 2 trial at 5 centers. SBRT consisted of 5 fractions of 7.4 Gy to a total dose of 37 Gy using conventional linear accelerators. Electromagnetic transponders were used for motion management. Health-related quality of life (HRQOL) was evaluated via the Expanded Prostate Cancer Index Composite 26 questionnaire. Acute and late toxicities were collected according to Common Terminology Criteria for Adverse Events, version 4.0. Linear mixed modeling was performed to assess changes in HRQOL over time. RESULTS: Median follow-up was 36 months. All men had low- or intermediate-risk disease. There have been 0 biochemical recurrences. No grade 3 urinary or bowel toxicity was reported. Twenty-three percent of patients had acute grade 2 urinary toxicity, with 9% late grade 2 urinary toxicity. Four percent and 5% experienced acute or late grade 2+ bowel toxicity, respectively. Urinary bother and bowel HRQOL transiently decreased during the first 6 to 12 months post-SBRT, and then returned to baseline. In men with good erectile function at baseline, sexual HRQOL declined during the first 6 months and stabilized thereafter. On linear mixed modeling, the strongest predictor of sustained bowel and sexual HRQOL was baseline HRQOL. CONCLUSIONS: In this multi-institutional phase 2 clinical trial using continuous real-time evaluation of prostate motion, prostate SBRT has excellent intermediate-term tumor control with mild and expected treatment-related side effects.

Code of Ethics for the American Association of Physicists in Medicine: report of Task Group 109.

A comprehensive Code of Ethics for the members of the American Association of Physicists in Medicine (AAPM) is presented as the report of Task Group 109 which consolidates previous AAPM ethics policies into a unified document. The membership of the AAPM is increasingly diverse. Prior existing AAPM ethics polices were applicable specifically to medical physicists, and did not encompass other types of members such as health physicists, regulators, corporate affiliates, physicians, scientists, engineers, those in training, or other health care professionals. Prior AAPM ethics policies did not specifically address research, education, or business ethics. The Ethics Guidelines of this new Code of Ethics have four major sections: professional conduct, research ethics, education ethics, and business ethics. Some elements of each major section may be duplicated in other sections, so that readers interested in a particular aspect of the code do not need to read the entire document for all relevant information. The prior Complaint Procedure has also been incorporated into this Code of Ethics. This Code of Ethics (PP 24-A) replaces the following AAPM policies: Ethical Guidelines for Vacating a Position (PP 4-B); Ethical Guidelines for Reviewing the Work of Another Physicist (PP 5-C); Guidelines for Ethical Practice for Medical Physicists (PP 8-D); and Ethics Complaint Procedure (PP 21-A). The AAPM Board of Directors approved this Code or Ethics on July 31, 2008.

Dedicated linear accelerator radiosurgery for the treatment of trigeminal neuralgia.

OBJECT: In this study the authors evaluate the efficacy of and complications associated with dedicated linear accelerator (LINAC) radiosurgery for trigeminal neuralgia (TN). METHODS: Between August 1995 and February 2001, 60 patients whose median age was 66.1 years (range 45-88 years) were treated with dedicated LINAC radiosurgery for TN. Forty-one patients (68.3%) had essential TN, 12 (20%) had secondary facial pain, and seven (11.7%) had atypical features. Twenty-nine patients (48.3%) had undergone previous surgical procedures. Radiation doses varied between 70 and 90 Gy (mean 83.3 Gy) at the isocenter, with the last 35 patients (58.3%) treated with a 90-Gy dose. A 5-mm collimator was used in 45 patients (75%) and a 7.5-mm collimator in 15 patients (25%). Treatment was focused at the nerve root entry zone. At last follow up (mean follow-up period 23 months, range 2-70 months), 36 (87.8%) of the 41 patients with essential TN had sustained significant pain relief (good plus excellent results). Twenty-three patients (56.1%) were pain free without medication (excellent outcome), 13 (31.7%) had a 50 to 90% reduction in pain with or without medication (good outcome), and five (12.2%) had minor improvement or no relief. Of 12 patients with secondary facial pain, significant relief was sustained in seven patients (58.3%); worse results were found with atypical pain. Fifteen (25%) of the 60 patients experienced new numbness postprocedure; no other significant complications were found. Pain relief was experienced at a mean of 2.7 months (range 0-12 months). CONCLUSIONS: Dedicated LINAC radiosurgery is a precise and effective treatment for TN.

Stereotactic radiotherapy for the treatment of lymphocytic hypophysitis. Report of two cases.

Lymphocytic hypophysitis is a rare inflammatory disorder of the pituitary gland. Standard therapy consists of transsphenoidal resection or oral administration of corticosteroid medications. Two patients with symptomatic lymphocytic hypophysitis, which recurred after standard therapy, were treated with low-dose stereotactic radiotherapy. On imaging studies both lesions demonstrated a response to radiation and each patient experienced relief of symptoms. There has been no adverse sequela of the radiation treatment. The authors conclude that stereotactic radiotherapy represents an effective, noninvasive treatment option for patients with lymphocytic hypophysitis, particularly if the disease is recurrent after surgery or resistant to corticosteroid medications.

An analysis of MCNP cross-sections and tally methods for low-energy photon emitters.

Monte Carlo calculations are frequently used to analyse a variety of radiological science applications using low-energy (10-1000 keV) photon sources. This study seeks to create a low-energy benchmark for the MCNP Monte Carlo code by simulating the absolute dose rate in water and the air-kerma rate for monoenergetic point sources with energies between 10 keV and 1 MeV. The analysis compares four cross-section datasets as well as the tally method for collision kerma versus absorbed dose. The total photon attenuation coefficient cross-section for low atomic number elements has changed significantly as cross-section data have changed between 1967 and 1989. Differences of up to 10% are observed in the photoelectric cross-section for water at 30 keV between the standard MCNP cross-section dataset (DLC-200) and the most recent XCOM/NIST tabulation. At 30 keV, the absolute dose rate in water at 1.0 cm from the source increases by 7.8% after replacing the DLC-200 photoelectric cross-sections for water with those from the XCOM/NIST tabulation. The differences in the absolute dose rate are analysed when calculated with either the MCNP absorbed dose tally or the collision kerma tally. Significant differences between the collision kerma tally and the absorbed dose tally can occur when using the DLC-200 attenuation coefficients in conjunction with a modern tabulation of mass energy-absorption coefficients.

Model 3500 125I brachytherapy source dosimetric characterization.

Low-energy gamma-emitting isotopes encapsulated for permanent implant are routinely applied in brachytherapy, most notably for prostate cancer. Before clinical use of a new source design, a full dosimetric analysis and standardized calibration are essential. Results of experimental measurement and analysis are reported here for the I-Plant (Implant Sciences Corporation) 125I source, model 3500. Dose measurements were made using standard methods employing thermoluminscent dosimeters in a water equivalent plastic phantom. Precision machined bores in the phantom located dosimeters and source(s) in a reproducible fixed geometry providing for transverse-axis and angular dose profiles over a range of distances from 0.17 to 10 cm. The data were analyzed in terms of parameters recommended by AAPM TG-43. The dose-rate constant, delta = 1.01 cGy/h U (+/-6%) (1 U = 1 cGy cm2 h(-1)), was evaluated with reference to a TG-51 calibrated 60Co standard, accounting for dosimeter response differences between 60Co and 125I photons. The radial dose function, g(r), the anisotropy function, F(r, theta), the anisotropy factor, phi(an)(r), and the point-source approximation anisotropy constant, phi(an), were derived from one- and two-dimensional dose distribution data measured in the phantom, accounting for finite dosimeter volume and with attention to inter-chip effects. The results confirm prior dosimetric characterization of the model 3500, and indicate that the new source is comparable to the MED3631-A/M and 6702 source designs and may substitute for model 6711 in permanent implants for the treatment of prostate cancer.

Dosimetric parameters of three new solid core I-125 brachytherapy sources.

Monte Carlo calculations and TLD measurements have been performed for the purpose of characterizing dosimetric properties of new commercially available brachytherapy sources. All sources tested consisted of a solid core, upon which a thin layer of 125I has been adsorbed, encased within a titanium housing. The PharmaSeed BT-125 source manufactured by Syncor is available in silver or palladium core configurations while the ADVANTAGE source from IsoAid has silver only. Dosimetric properties, including the dose rate constant, radial dose function, and anisotropy characteristics were determined according to the TG-43 protocol. Additionally, the geometry function was calculated exactly using Monte Carlo and compared with both the point and line source approximations. The 1999 NIST standard was followed in determining air kerma strength. Dose rate constants were calculated to be 0.955+/-0.005, 0.967+/-0.005, and 0.962+/-0.005 cGy h(-1) x U(-1) for the PharmaSeed BT-125-1, BT-125-2, and ADVANTAGE sources, respectively. TLD measurements were in excellent agreement with Monte Carlo calculations. Radial dose function, g(r), calculated to a distance of 10 cm, and anisotropy function, F(r,theta), calculated for radii from 0.5 to 7.0 cm, were similar among all source configurations. Anisotropy constants, phi(an), were calculated to be 0.941, 0.944, and 0.960 for the three sources, respectively. All dosimetric parameters were found to be in close agreement with previously published data for similar source configurations. The MCNP Monte Carlo code appears to be ideally suited to low energy dosimetry applications.

Initial clinical results of stereotactic radiotherapy for the treatment of craniopharyngiomas.

The efficacy and toxicity of stereotactic radiotherapy (SRT) for the treatment of craniopharyngioma has been retrospectively evaluated in 16 patients. The median tumor diameter was 2.8 cm (range 1.5-6.1) and the median tumor volume was 7.7 cc (range 0.7-62.8). SRT was delivered to a single isocenter using a dedicated 6 MV linear accelerator to patients immobilized with a relocatable stereotactic head frame. The three-year actuarial overall survival was 93% and the rate of survival free of any imaging evidence of progressive disease was 75%. The three-year actuarial survival rates free of solid tumor growth or cyst enlargement were 94% and 81% respectively. Our results suggest that SRT is a safe and effective treatment approach for patients with craniopharyngioma. Long-term follow-up is required to determine whether the normal tissue-sparing inherent with SRT results in reduction of the neurocognitive effects of conventional radiotherapy for craniopharyngioma. SRT can be delivered to craniopharyngioma that may be difficult to treat with stereotactic radiosurgery due to proximity of the optic chiasm. Further clinical experience is necessary to determine the clinical utility of beam shaping in the setting of SRT.