Dosimetric impact of rotational errors in trigeminal neuralgia radiosurgery using CyberKnife.

PURPOSE: Trigeminal neuralgia (TN) can be treated on the CyberKnife system using two different treatment delivery paths: the general-purpose full path corrects small rotations, while the dedicated trigeminal path improves dose fall-off but does not allow rotational corrections. The study evaluates the impact of uncorrected rotations on brainstem dose and the length of CN5 (denoted as Leff) covered by the prescription dose. METHODS AND MATERIALS: A proposed model estimates the delivered dose considering translational and rotational delivery errors for TN treatments on the CyberKnife system. The model is validated using radiochromic film measurements with and without rotational setup error for both paths. Leff and the brainstem dose is retrospectively assessed for 24 cases planned using the trigeminal path. For 15 cases, plans generated using both paths are compared for the target coverage and toxicity to the brainstem. RESULTS: In experimental validations, measured and estimated doses agree at 1%/1 mm level. For 24 cases, the treated Leff is 5.3 ± 1.7 mm, reduced from 5.9 ± 1.8 mm in the planned dose. Constraints for the brainstem are met in 23 cases for the treated dose but require frequent treatment interruption to maintain rotational corrections <0.5° using the trigeminal path. The treated length of CN5, and plan quality metrics are similar for the two paths, favoring the full path where rotations are corrected. CONCLUSIONS: We validated an analytical model that can provide patient-specific tolerances on rotations to meet plan objectives. Treatment using the full path can reduce treatment time and allow for rotational corrections.

Management of Very Early Small Cell Lung Cancer: A Canadian Survey Study.

Concurrent chemoradiotherapy (CRT) is the standard of care for limited-stage small cell lung cancer (LS-SCLC). Local therapy-surgery or stereotactic body radiotherapy (SBRT)-with adjuvant chemotherapy may be appropriate for very early (T1-T2, N0) disease. There is variability in the management of these cases, which may lead to variability in patient outcomes. This study aimed to determine practice patterns for the management of very early LS-SCLC in Canada. A survey was developed and distributed to Canadian medical and radiation oncologists specialising in lung cancer. The survey consisted of three sections: (1) physician demographics, (2) general practice approach, and (3) preferred approach for three clinical scenarios (1: peripheral T1 lesion; 2: central T1 lesion; 3: peripheral T2 lesion). Responses were analysed to detect differences across cases and among physician groups. There were 77 respondents. In case 1, assuming medical operability, most respondents (73%) chose surgery and adjuvant chemotherapy, with 19% choosing CRT. CRT was selected by a higher proportion in case 2 (48%) and case 3 (61%) (p < 0.05). If medically inoperable, most chose CRT over local therapy in all cases, with more choosing CRT in case 2 (84%) and case 3 (86%) than in case 1 (55%) (p < 0.05). Subgroup analysis showed a predilection towards CRT in Western Canada and among more experienced physicians, and towards SBRT in Ontario. There is variability in the management of very early LS-SCLC in Canada. CRT remains the most popular strategy in most cases, with surgery preferred for small peripheral lesions. Larger and more central tumours are more likely to be managed with CRT. Variation in practice is correlated with region and physician experience. Our study illustrates the variability in the management of very early LS-SCLC in Canada and highlights the need for more robust investigations into the ideal approach for these patients.

Primary Adenosquamous Carcinoma of the Prostate with Rectal Invasion.

Prostate adenosquamous carcinoma (pASC) is a rare form of prostate cancer accounting for <1% of all cases. It is generally considered an aggressive variant often presenting with significant symptom burden and/or metastatic disease. Given its rarity, optimal management of this cancer is unknown. We present a case of a patient with pASC treated with radiotherapy and chemotherapy with excellent symptomatic improvement and local control.

Stereotactic Body Radiotherapy (SBRT) in Very Limited-Stage Small Cell Lung Cancer (VLS-SCLC).

Small cell lung cancer (SCLC) is an aggressive neuroendocrine tumour with metastatic propensity. Stereotactic body radiation therapy (SBRT) is an emerging therapeutic option for SCLC, despite limited supporting evidence. By evaluating the use of SBRT in very limited stage (VLS) SCLC at our institution, we aimed to contribute to the existing knowledge in this area while establishing a basis for further research. We performed a retrospective review of all cases of VLS-SCLC treated with SBRT between 2013 and 2020. Baseline demographics, diagnostic, and treatment information were collected. The primary outcome was overall survival (OS). We identified 46 patients with pathologically confirmed VLS-SCLC; 25 were treated with SBRT, and the remainder received either surgery, conventional radiation therapy, chemotherapy, or palliative-intent therapy. After a median follow-up of 23.7 months, 44% of the patients had died; the median OS was of 24.4 months for the SBRT cohort and 67.0 months for the curative intent non-SBRT cohort. The difference in disease recurrence and survival between cohorts was underpowered and not statistically significant. Higher baseline ECOG and comorbidity was noted in the SBRT cohort.

Adrenal oligometastasis cured with stereotactic ablative radiotherapy.

Stereotactic ablative radiotherapy (SABR) has emerged as an effective, noninvasive alternative to surgery in patients with oligometastatic disease. Historically, select patients with adrenal oligometastases have been treated with adrenalectomies which can offer durable local control and reasonable survival rates. SABR is a promising noninvasive treatment alternative to surgery capable of delivering ablative doses of radiation to the tumor with the goal of achieving durable local control of adrenal metastases. We report on a case of a patient who underwent initial surgical resection for a locally advanced lung adenocarcinoma and subsequently developed an early, biopsy-proven, oligometastatic recurrence in the adrenal gland. He underwent chemotherapy and SABR using CyberKnife to the adrenal metastasis and is in remission 7 years after treatment with no late toxicity. Fractionated SABR is an attractive noninvasive alternative to surgery for adrenal metastases. This case demonstrates that select patients with adrenal oligometastases, can achieve long-term remission and even cure following SABR.

Delayed pseudoprogression of a vestibular schwannoma postradiosurgery.

Radiosurgery (RS) can offer excellent local control in the management of both benign and malignant tumors measuring less than 3 cm in size. A known late complication of radiosurgery is radiation necrosis which generally occurs within 6-18 months following treatment and has an increased risk of occurrence with higher radiation doses. The lower dose used to treat vestibular schwannomas (VS) makes this complication less frequent. Tumors that do not respond to radiosurgery and continue to grow may require surgical intervention. We report a case of a young male who received radiosurgery (18 Gy in 3 fractions) in February 2016 for a recurrent VS following initial debulking surgery in 2008. Follow-up imaging revealed an interval decrease in size by May 2017; however, by April 2018, there was significant interval increase in the cisternal components of the tumor. By September 2018, the lesion had increased by >50% (to a size of 29 mm) compared to May 2017. The patient agreed to undergo repeat surgical debulking. Upon review of the preoperative MRI, the cisternal component of the tumor had substantially decreased in size. Although uncommon, this reflects delayed, pseudoprogression which, in our case, was self-limiting. This raises a question regarding when to proceed with surgical intervention of growing VS following radiosurgery given the potential for delayed resolution of radiation necrosis and demonstrates a gap in our current literature involving surgery of VS following radiosurgery.

MultiHance as a contrast alternative for Gadovist allergic patients.

The dramatic rise in the use of contrast agents for diagnostic imaging within the last decade has largely contributed to the effectiveness of MR imaging, however even with the use of prophylaxis, adverse reactions to contrast, including anaphylaxis, still occur. We describe the case of a 46-year-old female patient with a hemangiopericytoma requiring ongoing contrast MR surveillance, and a documented anaphylactic reaction to Gadovist (gadobutrol injection) despite premedication. Allergy testing was positive to intradermal undiluted Gadovist, confirming an IgE-mediated Gadovist allergy, with subsequent skin testing by prick and intradermal negative to undiluted MultiHance. She went on to receive MultiHance prior to her subsequent MRI scans without clinical reaction and without premedication, demonstrating that there may be superior alternatives to traditionally used gadolinium dyes in patients with moderate to severe reactions, and warrants further investigation into the anaphylactoid characteristics between the different gadolinium-based contrast agents.

Impact of adipose tissue on prostate cancer aggressiveness - analysis of a high-risk population.

Background We investigated whether visceral adiposity is associated with more aggressive disease at prostatectomy. Materials and methods Four hundred and seventy-four patients referred for postoperative adjuvant or salvage radiotherapy were included in this study. Primary endpoints were positive surgical margins (pSM) or extracapsular extension (ECE). Visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) were manually contoured. Univariate and multivariate logistic regression was performed. Results In univariate analysis, VAT volume (p = 0.006), adipose tissue ratio (VAT/SAT, p = 0.003), density of the SAT (p = 0.04), as well as age (p < 0.001) were associated with pSM. In the univariate analysis, SAT density was associated with a trend towards a higher rate of ECE (p = 0.051) but visceral fat volume (p = 0.01), as well as the adipose tissue ratio (p = 0.03) were both protective factors. None of the adipose tissue measurements or BMI had an influence on biochemical recurrence or overall survival (all p ≥ 0.5). Conclusions SAT-volume and increased SAT-density were generally associated with more aggressive prostate cancers whereas VAT as a protective factor. These findings emphasize a possible mechanism for the association between obesity and prostate cancer aggressiveness.

Hypofractionation for prostate cancer: an update.

INTRODUCTION: Recent advances in image guided radiation therapy (IGRT) has prompted much interest in the use of high-dose-per-fraction regimens for prostate cancer. Furthermore, from a radiobiological standpoint, there is increasing evidence that prostate tumors have a relatively low ɑ/ß ratio therefore, the use of hypofractionation may potentially offer acceptable tumor control while minimizing late toxicity to critical structures. Areas covered: This expert review explores the current evidence regarding the safety and efficacy of hypofractionated radiotherapy for prostate cancer. A particular emphasis was placed on large, randomized phase III trials as these are most likely to influence clinical practice. The authors discuss the use of both moderate and extreme hypofractionation. Expert commentary: The recent publication of 5-year outcomes from large prospective trials of moderate hypofractionation enhances our confidence that these techniques are both safe and effective. We recommend the fractionation scheme of 60 Gy in 20 fractions as this regimen was not associated with any notable increase in late toxicity. With respect to extreme hypofractionation, mature phase III trials are needed to demonstrate the safety and efficacy of these techniques. For now, the use of radiosurgery should be limited to participation in prospective clinical trials.

Limitations of Personalized Medicine and Gene Assays for Breast Cancer.

Adjuvant systemic treatments reduce the risk of breast cancer recurrence following the local treatment of primary stage I-III breast cancers. For patients with hormone-positive breast cancers receiving hormonal therapy, the risk of distant recurrence is under 20% and therefore, many patients may potentially be spared of chemotherapy. Consequently, several molecular signatures based on gene expression were developed to better determine which breast cancer patients would benefit from chemotherapy. We present the case of a 62-year-old woman diagnosed with an early stage hormone receptor-positive breast cancer that was treated with a partial mastectomy. Oncotype DX (Genomic Health, Redwood City, CA) molecular testing was performed on the surgical specimen, which reported a recurrence score of 0. The patient commenced adjuvant radiotherapy during which she developed symptoms suggestive of bone metastasis and was subsequently diagnosed with a spinal cord compression that required neurosurgery and radiotherapy. Pathology review of the specimen from the spine surgery revealed a metastatic breast carcinoma with neuroendocrine differentiation. Molecular assays such as Oncotype DX are increasingly used to prognosticate patient outcomes and help determine who may avoid chemotherapy. This case report seeks to illustrate that such assays should not be used in the presence of rare histological subtypes like neuroendocrine breast cancers, which are often under-reported. The current status of personalized medicine and gene assays in breast cancer is reviewed and potential strategies are suggested to identify these rare cases to better orient diagnostic and treatment decisions.

External validation of the ProCaRS nomograms and comparison of existing risk-stratification tools for localized prostate cancer.

INTRODUCTION: The purpose of this study was to perform a direct comparison of several existing risk-stratification tools for localized prostate cancer in terms of their ability to predict for biochemical failure-free survival (BFFS). Two large databases were used and an external validation of two recently developed nomograms on an independent cohort was also performed in this analysis. METHODS: Patients who were treated with external beam radiotherapy (EBRT) and/or brachytherapy for localized prostate cancer were selected from the multi-institutional Genitourinary Radiation Oncologists of Canada (GUROC) Prostate Cancer Risk Stratification (ProCaRS) database (n=7974) and the Centre Hospitalier de l'Université de Montréal (CHUM) validation database (n=2266). The primary outcome was BFFS using the Phoenix definition. Concordance index (C-index) reported from Cox proportional hazards regression using 10-fold cross validation and decision curve analysis (DCA) were used to predict BFFS. RESULTS: C-index identified Cancer of the Prostate Risk Assessment (CAPRA) score and ProCaRS as superior to the historical GUROC and National Comprehensive Cancer Network (NCCN) risk-stratification systems. CAPRA modeled as five and three categories were superior to GUROC and NCCN only for the CHUM database. C-indices for CAPRA score, ProCaRS, GUROC, and NCCN were 0.72, 0.72, 0.71, and 0.72, respectively, for the ProCaRS database, and 0.66, 0.63, 0.57, and 0.60, respectively, for the CHUM database. However, many of these comparisons did not demonstrate a clinically meaningful difference. DCA identified minimal differences across the different risk-stratification systems, with no system emerging with optimal net benefit. External validation of the ProCaRS nomograms yielded favourable calibrations of R2=0.778 (low-dose rate [LDR]-brachytherapy) and R2=0.868 (EBRT). CONCLUSIONS: This study externally validated two ProCaRS nomograms for BFFS that may help clinicians in treatment selection and outcome prediction. A direct comparison between existing risk-stratification tools demonstrated minimal clinically significant differences in discriminative ability between the systems, favouring the CAPRA and ProCaRS systems. The incorporation of novel prognostic variables, such as genomic markers, is needed.

Helical tomotherapy and volumetric modulated arc therapy: New therapeutic arms in the breast cancer radiotherapy.

AIM: To analyse clinical and dosimetric results of helical tomotherapy (HT) and volumetric modulated arc therapy (VMAT) in complex adjuvant breast and nodes irradiation. METHODS: Seventy-three patients were included (31 HT and 42 VMAT). Dose were 63.8 Gy (HT) and 63.2 Gy (VMAT) in the tumour bed, 52.2 Gy in the breast, 50.4 Gy in supraclavicular nodes (SCN) and internal mammary chain (IMC) with HT and 52.2 Gy and 49.3 Gy in IMC and SCN with VMAT in 29 fractions. Margins to particle tracking velocimetry were greater in the VMAT cohort (7 mm vs 5 mm). RESULTS: For the HT cohort, the coverage of clinical target volumes was as follows: Tumour bed: 99.4% ± 2.4%; breast: 98.4% ± 4.3%; SCN: 99.5% ± 1.2%; IMC: 96.5% ± 13.9%. For the VMAT cohort, the coverage was as follows: Tumour bed: 99.7% ± 0.5%, breast: 99.3% ± 0.7%; SCN: 99.6% ± 1.4%; IMC: 99.3% ± 3%. For ipsilateral lung, Dmean and V20 were 13.6 ± 1.2 Gy, 21.1% ± 5% (HT) and 13.6 ± 1.4 Gy, 20.1% ± 3.2% (VMAT). Dmean and V30 of the heart were 7.4 ± 1.4 Gy, 1% ± 1% (HT) and 10.3 ± 4.2 Gy, 2.5% ± 3.9% (VMAT). For controlateral breast Dmean was 3.6 ± 0.2 Gy (HT) and 4.6 ± 0.9 Gy (VMAT). Acute skin toxicity grade 3 was 5% in the two cohorts. CONCLUSION: HT and VMAT in complex adjuvant breast irradiation allow a good coverage of target volumes with an acceptable acute tolerance. A longer follow-up is needed to assess the impact of low doses to healthy tissues.

Influence of body mass index and periprostatic fat on rectal dosimetry in permanent seed prostate brachytherapy.

PURPOSE: We examined the influence of body mass index (BMI) and body fat distribution on rectal dose in patients treated with permanent seed brachytherapy for localized prostate cancer. METHODS AND MATERIALS: We analyzed 213 patients treated with I125 seed brachytherapy for localized prostate cancer. BMI and rectal dosimetry data for all patients were available. Data on visceral and subcutaneous fat distribution at the level of the iliac crest (n = 140) as well as the distribution of periprostatic and subcutaneous fat at the symphysis pubis level were obtained (n = 117). Fat distribution was manually contoured on CT on day 30 after brachytherapy. The correlation between BMI, fat distribution and rectal dose (R100 (in cc), R150 (cc), D2 (Gy)) was analyzed using the Spearman correlation coefficient. Differences in rectal dose between tertiles of body fat distribution were calculated using nonparametric tests. RESULTS: Periprostatic adipose was only weakly correlated with BMI (r = 0.0.245, p = 0.008) and only weakly correlated with the other fat measurements (r = 0.31-0.37, p < 0.001). On the other hand, BMI was correlated with all other fat measurements (≥0.58, p < 0.001). All the other fat measurements were strongly correlated with each other (r = 0.5-0.87, p < 0.001). Patients with an R100 of >1.3 cc (23% of patients) had less visceral fat (p = 0.004), less subcutaneous fat at the level of the iliac crest (p = 0.046) and a lower BMI (26.8 kg/m2 vs. 28.5 kg/m2, p = 0.02) than patients with an R100 of <1.3 cc. Results were very similar when comparing an R100 of >1.0 cc (34% of patients) across the tertiles. None of the tested linear regression models were predictive (max 12%) of dose to the rectum. CONCLUSION: Dose to the rectum is dependent on BMI and body fat distribution. Periprostatic fat does not influence rectal dose. Dose to the rectum remains difficult to predict and depends on many factors, one of which is body fat distribution.

Impact of concurrent androgen deprivation on fiducial marker migration in external-beam radiation therapy for prostate cancer.

PURPOSE: To determine the extent of gold fiducial marker (FM) migration in patients treated for prostate cancer with concurrent androgen deprivation and external-beam radiation therapy (EBRT). METHODS AND MATERIALS: Three or 4 gold FMs were implanted in 37 patients with prostate adenocarcinoma receiving androgen deprivation therapy (ADT) in conjunction with 70-78 Gy. Androgen deprivation therapy was started a median of 3.9 months before EBRT (range, 0.3-12.5 months). To establish the extent of FM migration, the distance between each FM was calculated for 5-8 treatments once per week throughout the EBRT course. For each treatment, the distance between FMs was compared with the distance from the digitally reconstructed radiographs generated from the planning CT. A total of 281 treatments were analyzed. RESULTS: The average daily migration was 0.8 ± 0.3 mm, with distances ranging from 0.2 mm-2.6 mm. Two of the 281 assessed treatments (0.7%) showed migrations >2 mm. No correlation between FM migration and patient weight or time delay between ADT and start of EBRT was found. There was no correlation between the extent of FM migration and prostate volume. CONCLUSION: This is the largest report of implanted FM migration in patients receiving concomitant ADT. Only 0.7% of the 281 treatments studied had significant marker migrations (>2 mm) throughout the course of EBRT. Consequently, the use of implanted FMs in these patients enables accurate monitoring of prostate gland position during treatment.