The impact of national holidays on postoperative radiotherapy of squamous cell carcinoma of the head and neck.

Background: Delays in starting postoperative radiotherapy (PORT) have been established as negative predictors for clinical outcomes in head and neck squamous cell carcinomas (HNSCC). Our study aimed to examine the effect of delays during PORT, and the impact of national holidays in Canada, a publicly funded system, on oncologic outcomes such as Overall Survival (OS) and Local Recurrence (LR). Methods: The provincial cancer registry was queried to obtain demographic, pathologic, and outcomes data from cancer patients treated for all squamous cell carcinomas of the head and neck region treated between January 1, 2007 and November 30, 2019. All extracted information was cross-referenced and supplemented by chart review of patient electronic medical records. Extracted data were analyzed for OS and LR, in the context of Canadian national holidays causing delays during PORT. Results: 1433 patients treated for HNSCCs were identified, of whom 338 were treated curatively with surgery followed by PORT. 68.6% of patients experienced at least one day of interruption during treatments due to holidays. LR was 15.4% and OS was 59.6% at 5 years. Treatment interruptions by holidays were predictive of local recurrence (HR, 2.38; 95% CI 1.17-4.83; p = 0.017). Patients that developed early recurrence prior to PORT had very poor oncologic outcomes. Conclusion: Our findings were consistent with previously published studies in limiting the interval between surgery and PORT. We identified the novel finding of paired holidays as a significant predictor in determining LR, suggesting the importance of modifying RT delivery schedules and timing.

Sequence Inversion to Facilitate Concurrent Radiotherapy and Systemic Therapy. A Proof of Principle Study in the Setting of a Phase II Randomized Trial in Prostate Cancer.

Background: Concomitant chemo-radiation for pelvic cancers remains challenging to be delivered at full doses. We hypothesized that fewer delays in chemotherapy would occur if the sequence of radiotherapy would be reversed, starting with the boost volume followed by the elective nodal volume. We report the result of a Phase II randomized study for high risk prostate cancer. Patients and Method: The study was a double-blinded phase II randomized trial. Patients were eligible if they had non-metastatic high-risk prostate cancer. All patients received 2.5 years of hormonal therapy and 46.5 Gy in 25 fractions to the pelvic lymph nodes. Patients received a radiation boost to the prostate, either before or after whole pelvic irradiation. Concurrent (20 mg/m2) Docetaxel was given on the first day of radiotherapy and weekly thereafter for a total of eight treatments until predefined toxicity stopping rules. Results: Ninety patients were included and randomized. Four were ineligible for the analysis. In total, 42 patients were randomized to the standard sequence, 44 patients to the experimental sequence. There were statistically fewer GI or GU toxicities leading to a docetaxel dose reduction or omission in the experimental sequence compared to the standard sequence, 5 vs. 15 events (p = 0.027). There was no difference in overall survival, cause-specific survival, or biochemical-relapse free survival between the two sequences. Conclusions: This is the first study to test sequence inversion for pelvic radio-chemotherapy in a randomized double-blind trial. Less chemotherapy interruptions or dose reductions occurred by inverting the radiation sequence of the large field and the boost. The trial was registered with Clinicaltrials.gov: NCT00452556.

Testosterone Suppression with Luteinizing Hormone-Releasing Hormone (LHRH) Agonists in Patients Receiving Radiotherapy for Prostate Cancer.

OBJECTIVES: To characterize the probability of testosterone escape during a course of radiotherapy and androgen deprivation (ADT) in patients with prostate cancer, and examine predictors of testosterone escape, the prostate specific antigen (PSA) levels during testosterone escape, and the impact of testosterone escape on outcome. PATIENTS AND METHODS: To participate in the database review, necessary data included: (i) type of luteinizing hormone-releasing hormone agonist (LHRHa) administered, date of initiation, and date of cessation or duration of therapy, (ii) radiotherapy information (start date and dose) with at least 6 months of follow-up after radiotherapy, (iii) radiotherapy to the prostate or prostate bed, and (iv) at least one serum testosterone and PSA measurement. RESULTS: Five hundred sixty patients in the database were identified as being treated with radiotherapy and ADT. Three hundred seventy-five patients had at least one measurement of testosterone and PSA, and the type of LHRHa used could be determined in 361 patients. Median follow-up of patients still living was 4.7 years. The median number of testosterone measurements per patient was six. The incidence of testosterone escape per patient course of treatment was buserelin, 9.3%; goserelin, 10.5%; intramuscular leuprolide, 11.5%; leuprolide subcutaneous, 23.9%; and triptorelin, 6.7% (p = 0.02). There was no difference in either biochemical failure-free survival or overall survival in patients stratified by testosterone escape. The modal PSA level during a testosterone escape was an undetectable PSA. CONCLUSIONS: An undetectable PSA does not rule out the presence of higher than desired levels of testosterone during ADT. In this cohort of patients, there appears to be no impact of testosterone escape on either biochemical relapse-free survival or overall survival.

A pan-Canadian survey of peer review practices in radiation oncology.

PURPOSE: Peer review (PR) of treatment plans has been recognized internationally as a key component of quality care in radiation oncology programs (ROPs). We conducted a survey of Canadian ROPs to describe current PR practices and identify barriers/facilitators to PR optimization. METHODS AND MATERIALS: A 42-item e-survey was sent to all Canadian ROPs (n = 44). Survey development was guided by expert consensus, literature review, and existing guidelines. One multidisciplinary response per ROP was requested. RESULTS: Response rate was 100.0% (44/44). All ROPs (100.0%) reported conducting some PR and rated its importance as 7/10 or higher (10 = extremely important). One-half of ROPs (52.3%) peer-reviewed >80% of curative treatment plans. ROPs reported performing PR "always/almost always" pretreatment (38.6%) or before 25% of radiation therapy delivery (52.3%). The majority of ROPs reported recommending major plan changes in <5% of plans (88.6%) and documenting findings in the medical record (58.1%). Barriers to PR were radiation oncologist availability (34.1%) and time constraints (27.3%). Facilitators included development of PR standards (97.7%) and education/support (90.9%). CONCLUSIONS: The ROPs perceive PR as highly important, but substantial variation in the extent, timing, and documentation of PR exists. The understanding of current PR activities, barriers, and facilitators will inform the development of initiatives to optimize PR in radiation oncology.

Investigating the Impact of Positron Emission Tomography-Computed Tomography Versus Computed Tomography Alone for High-risk Volume Selection in Head and Neck and Lung Patients Undergoing Radiotherapy: Interim Findings.

INTRODUCTION: The aim of this study was to quantify the impact of positron emission tomography-computed tomography (PET-CT) on clinical target volume (CTV) selection in non-small cell lung cancer (NSCLC) and head and neck squamous cell cancer (HNSCC) cancer patients. METHODS: Eight radiation oncologists with expertise in either NSCLC or HNSCC prospectively contoured target volumes with and without PET-CT findings. All volumes were contoured manually, and computed tomography (CT)-alone contours were identified as gross tumour volume CT and clinical target volume (CTV) CT, whereas those contoured with the aid of PET-CT were GTV PET and CTV PET. PET-CT contours were used for actual treatment delivery. Test treatment plans were generated based on the CT-alone volumes and applied to the final PET-CT contours. PET-CT had an impact if the test plans failed department quality assurance guidelines. For each patient, the dose to critical structures and any changes in the treatment plan were recorded. RESULTS: Eighty patients (49 HNSCC and 31 NSCLC) were analyzed. PET-CT impacted 42.9% of HNSCC cases and 45.2% of NSCLC cases. On average, PET-CT volumes were significantly larger than CT-alone volumes for HNSCC cases (P < .01) but not for NSCLC cases (P = .29). For organs at risk, no statistically significant differences were noted, with the exception of mean parotid dose for the right and left parotids (P = .0137and P = .0330, respectively). CONCLUSIONS: Interim analysis of data found that the use of PET-CT in the radiation therapy planning process impacted CTV selection, resulting in a major change in radiation therapy plans in 43.7% (HNSCC 42.9% and NSCLC 45.2%) of patients.

Phase II study of accelerated hypofractionated three-dimensional conformal radiotherapy for stage T1-3 N0 M0 non-small cell lung cancer: NCIC CTG BR.25.

BACKGROUND: A multi-institutional phase II trial was performed to assess a hypofractionated accelerated radiotherapy regimen for early stage non-small cell lung cancer (NSCLC) in an era when stereotactic body radiotherapy was not widely available. METHODS: Eighty patients with biopsy-proven, peripherally located, T1-3 N0 M0 NSCLC were enrolled. Eligible patients received 60 Gy in 15 fractions using a three-dimensional conformal technique without inhomogeneity correction. The gross tumour volume (GTV) was the primary tumor only, and the planning target volume (PTV) margin was 1.0 to 1.5cm. The primary endpoint was the 2-year primary tumor control rate. Toxicities were measured using the Common Terminology Criteria for Adverse Events version 3.0. RESULTS: The median follow-up of patients was 49 months (range = 21-63 months). The median age of patients was 75.9 years. The actuarial rate of primary tumor control was 87.4% (95% confidence interval [CI] = 76.2% to 93.5%) at 2 years. Overall survival was 68.7% (95% CI = 57.2% to 77.6%) at 2 years. The actuarial rates of developing regional and distant relapse at 2 years were 8.8% (95% CI = 4.1% to 18.7%) and 21.6% (95% CI = 13.5% to 33.5%), respectively. Tumor size greater than 3cm was associated with an increased risk of developing distant relapse (hazard ratio = 3.11; 95% CI = 1.30 to 7.42; two-sided log-rank test P = .007). The most common grade 3+ toxicities were fatigue (6.3%), cough (7.5%), dyspnea (13.8%), and pneumonitis (10.0%) CONCLUSIONS: Conformal radiotherapy to a dose of 60 Gy in 15 fractions resulted in favorable primary tumor control and overall survival rates in patients with T1-3 N0 M0 NSCLC. Severe toxicities were uncommon with this relatively simple treatment technique.

Spatial and dosimetric variability of organs at risk in head-and-neck intensity-modulated radiotherapy.

PURPOSE: The accuracy of intensity-modulated radiotherapy (IMRT) delivery may be compromised by random spatial error and systematic anatomic changes during the treatment course. We present quantitative measurements of the spatial variability of head-and-neck organs-at-risk and demonstrate the resultant dosimetric effects. METHODS AND MATERIALS: Fifteen consecutive patients were imaged weekly using computed tomography during the treatment course. Three-dimensional displacements were calculated for the superior and inferior brainstem; C1, C6, and T2 spinal cord; as well as the lateral and medial aspects of the parotid glands. The data were analyzed to show distributions of spatial error and to track temporal changes. The treatment plan was recalculated on all computed tomography sets, and the dosimetric error was quantified in terms of the maximal dose difference (brainstem and spinal cord) or the mean dose difference and the volume receiving 26 Gy (parotid glands). RESULTS: The mean three-dimensional displacement was 2.9 mm for the superior brainstem, 3.4 mm for the inferior brainstem, 3.5 mm for the C1 spine, 5.6 mm for the C6 spine and 6.0 mm for the T2 spine. The lateral aspects of both parotid glands showed a medial translation of 0.85 mm/wk, and glands shrank by 4.9%/wk. The variability of the maximal dose difference was described by standard deviations ranging from 5.6% (upper cord) to 8.0% (lower cord.) The translation of the left parotid resulted in an increase of the mean dose and the volume receiving 26 Gy. CONCLUSION: Random spatial and dosimetric variability is predominant for the brainstem and spinal cord and increases at more inferior locations. In contrast, the parotid glands demonstrated a systematic medial translation during the treatment course and thus sparing may be compromised.

Optimized radiation of pelvic volumes in the clinical setting by using a novel bellyboard with integrated gonadal shielding.

The purpose of this study was to determine the feasibility of a custom-made, modified bellyboard to reduce radiotherapy side effects on small bowel, bladder, skin, and male gonads. Two groups of 10 consecutive patients each were treated from January 2003 through April 2003 with neoadjuvant (45 Gy) or adjuvant (54 Gy) radio(chemo)therapy in single fractions of 5 days a week 1.8 Gy for rectal carcinoma, using a photon energy of 15 MV. One group was positioned in a prone position without an immobilization device, the other group was positioned on our bellyboard. Treatment planning was calculated by using a 4- and a 3-field box technique. Differences in the dose of organs of risk were calculated. For 1 male patient, a gonadal shielding was developed and integrated. All patients examined with the bellyboard demonstrated an anterior and cranial dislocation of the small bowel. Using a 4-field box, the mean dose to the small bowel of patients treated on our bellyboard was 56.5% as compared to 63.1% when treated without the bellyboard. When a 3-field box was used, the mean dose to the small bowel was 52.4% when the bellyboard was used, as compared to a mean dose of 63.1% without the bellyboard. Regarding the dose volume effects to the bladder, the mean dose for patients treated with a 4-field box was about 14.5% higher as compared to patients treated with a 3-field box. The mean dose to the hip joints and skin also depended on the radiation technique. The patient who received gonadal shielding received a maximal total gonadal dose of about 75.0 cGy in single fractions of maximal 3.0 cGy (TL-dosimeters). Daily setup variations evaluated by a beam's-eye view were similar in both groups and ranged from 0.5 cm 1.0 cm. For daily use, our bellyboard appears to be an ideal compromise due to effectiveness, its easy handling, and reproductive positioning; moreover, it can also be used in combination with gonadal shielding.