M. Yassa

Hypofractionated Radiation Therapy for Breast Ductal Carcinoma In Situ

PURPOSE Conventional radiation therapy (RT) administered in 25 fractions after breast-conserving surgery (BCS) is the standard treatment for ductal carcinoma in situ (DCIS) of the breast. Although accelerated hypofractionated regimens in 16 fractions have been shown to be equivalent to conventional RT for invasive breast cancer, few studies have reported results of using hypofractionated RT in DCIS. METHODS AND MATERIALS In this multicenter collaborative effort, we retrospectively reviewed the records of all women with DCIS at 3 institutions treated with BCS followed by hypofractionated whole-breast RT (WBRT) delivered in 16 fractions. RESULTS Between 2003 and 2010, 440 patients with DCIS underwent BCS followed by hypofractionated WBRT in 16 fractions for a total dose of 42.5 Gy (2.66 Gy per fraction). Boost RT to the surgical bed was given to 125 patients (28%) at a median dose of 10 Gy in 4 fractions (2.5 Gy per fraction). After a median follow-up time of 4.4 years, 14 patients had an ipsilateral local relapse, resulting in a local recurrence-free survival of 97% at 5 years. Positive surgical margins, high nuclear grade, age less than 50 years, and a premenopausal status were all statistically associated with an increased occurrence of local recurrence. Tumor hormone receptor status, use of adjuvant hormonal therapy, and administration of additional boost RT did not have an impact on local control in our cohort. On multivariate analysis, positive margins, premenopausal status, and nuclear grade 3 tumors had a statistically significant worse local control rate. CONCLUSIONS Hypofractionated RT using 42.5 Gy in 16 fractions provides excellent local control for patients with DCIS undergoing BCS.

Combined Hypofractionated Radiation and Hormone Therapy for the Treatment of Intermediate-Risk Prostate Cancer

PURPOSE Because of the low alpha/beta value of prostate cancer, a therapeutic gain may be possible with a hypofractionated radiation scheme, and this gain may be further increased with the adjunct of hormone therapy. A Phase II study was undertaken to study the toxicity of such a treatment. METHODS AND MATERIALS Forty-two patients with intermediate-risk prostate cancer were recruited for this study. Neoadjuvant and concomitant hormone therapy consisted of one injection of leuprolide acetate (4-month preparation) and 1 month of oral nonsteroidal, anti-androgen medication starting on the day of the injection. Radiation treatment was started 8 weeks after the injection and patients received 57 Gy in 19 fractions. RESULTS Median follow-up was 46 months. The treatment was well tolerated and no interruptions occurred. The majority (59%) had Grade 0 or 1 acute genitourinary (GU) toxicity, whereas 36% had Grade 2 and 5% had Grade 3 acute GU toxicity. Only Grade 1 or 2 gastrointestinal toxicity was seen. All chronic toxicity was of Grade 1 or 2 except for 3 patients (8%) with Grade 3 toxicity. Sixty-eight percent (68%) of patients had no long-term side effects from the treatment. At time of analysis, 79% showed no sign of treatment failure. CONCLUSIONS Hypofractionated radiation with neoadjuvant and concomitant hormone therapy is well tolerated with no significant short- or long-term morbidity. Control for this risk group is good, and comparative Phase III studies should be undertaken to determine whether this treatment is superior to new evolving treatments.

Association of Radiotherapy Boost for Ductal Carcinoma In Situ With Local Control After Whole-Breast Radiotherapy

Importance The use of a radiotherapy (RT) boost to the tumor bed after whole-breast RT (WBRT) for ductal carcinoma in situ (DCIS) is largely extrapolated from invasive cancer data, but robust evidence specific to DCIS is lacking. Objective To compare ipsilateral breast tumor recurrence (IBTR) in women with DCIS treated with vs without the RT boost after breast-conserving surgery and WBRT. Design, Setting, and Participants This retrospective analysis pooled deidentified patient-level data from 10 academic institutions in the United States, Canada, and France from January 1, 1980, through December 31, 2010. All patients had newly diagnosed pure DCIS (no microinvasion), underwent breast-conserving surgery, and received WBRT with or without the boost with a minimum of 5 years of follow-up required for inclusion in the analysis. Given the limited events after WBRT, an a priori power analysis was conducted to estimate the DCIS sample size needed to detect the anticipated benefit of the boost. Data were uniformly recoded at the host institution and underwent primary and secondary reviews before analysis. Sample size calculations (ratio of patients who received the boost dose to those who did not, 2:1; &agr; = .05; power = 80%) estimated that 2982 cases were needed to detect a difference of at least 3%. The final analysis included 4131 patients (2661 in the boost group and 1470 in the no-boost group) with a median follow-up of 9 years and media boost dose of 14 Gy. Data were collected from July 2011 through February 2014 and analyzed from March 2014 through August 2015. Interventions Radiotherapy boost vs no boost. Main Outcomes and Measures Ipsilateral breast tumor recurrence. Results The analysis included 4131 patients (median [SD] age, 56.1 [10.9] years; range, 24-88 years). Patients with positive margins, unknown estrogen receptor status, and comedo necrosis were more likely to have received an RT boost. For the entire cohort, the boost was significantly associated with lower IBTR (hazard ratio [HR], 0.73; 95% CI, 0.57-0.94; P = .01) and with IBTR-free survival (boost vs no-boost groups) of 97.1% (95% CI, 0.96-0.98) vs 96.3% (95% CI, 0.95-0.97) at 5 years, 94.1% (95% CI, 0.93-0.95) vs 92.5% (95% CI, 0.91-0.94) at 10 years, and 91.6% (95% CI, 0.90-0.93) vs 88.0% (95% CI, 0.85-0.91) at 15 years. On multivariable analysis accounting for confounding factors, the boost remained significantly associated with reduced IBTR (HR compared with no boost, 0.68; 95% CI, 0.50-0.91; P = .01) independent of age and tamoxifen citrate use. Conclusions and Relevance This patient-level analysis suggests that the RT boost confers a statistically significant benefit in decreasing IBTR across all DCIS age groups, similar to that seen in patients with invasive breast cancer. These findings suggest that a DCIS RT boost to the tumor bed could be considered to provide an added incremental benefit in decreasing IBTR after a shared discussion between the patient and her radiation oncologist.

Fiducial marker implantation in prostate radiation therapy: complication rates and technique.

PURPOSE This study aims to report the complication rate from the transrectal ultrasound-guided implantation of gold seed markers in prostate radiotherapy, as well as describing the technique used. MATERIALS AND METHODS Between May 2010 and December 2012, 169 patients with localized prostate cancer had an intraprostatic fiducial marker implantation under transrectal ultrasound guidance. The procedure included prophylactic antibiotic therapy, fleet enema, implantation performed by trained radiation oncologists at our center prior to image-guided radiotherapy. Toxicity occurring between implantation and subsequent radiotherapy start date was assessed. The following parameters were analyzed via medical chart review: antibiotic therapy, anticoagulant interruption, bleeding, pain, prostate volume, number of markers implanted, post-implantation complications and delay before starting radiotherapy. RESULTS Of the 169 men, 119 (70.4%) underwent insertion of 4 fiducial markers and the other 50 (29.6%) had 3. The procedure was well-tolerated. There was no interruption of the implantation with regards to pain or hemorrhage. No grade 3 or 4 complications were observed. Seed migration rate was 0.32%, for the migration of 2 markers on 626 implanted. Mean prostate volume was 38 cm(3) (range: 10-150 cm(3)). Two patients (1.18%) developed a urinary tract infection following the procedure: prostate volume of 25 and 65 cm(3), four gold seed markers implanted, urinary tract infection resistant to prophylactic antibiotherapy, and treated with antibiotics specific to their infection as determined on urine culture. CONCLUSION Transrectal fiducial marker implantation for image-guided radiotherapy in prostate cancer is a well-tolerated procedure without major associated complications.

Two-Year Clinical Experience With Tomotherapy: The French National Cancer Institute Project on Implementing New Technology

The pooled 2-year clinical experience using three tomotherapy units installed in France in 2007 is presented. Treatment indications and protocols were devised for each disease site and were the result of a consensus. A total of 642 patients were treated for central nervous system, head and neck, thoracic, abdominal, and pelvic tumors. Overall, grade 3, 4, and 5 acute toxicity was 10.7%, 0.3%, and 0.2%, respectively. Grade 3 chronic toxicity was 1.2%. There was no grade 4 or 5 chronic toxicity. The use of tomotherapy in a broad clinical practice is safe, and acute and chronic toxicity both are acceptable for all anatomical locations.

Hypofractionated radiotherapy in prostate cancer.

In regards to prostate cancer, the classic radiotherapy dose ranges from 70–80 Gy, administered in daily 2-Gy fractions. However, when taking into account the particular radiobiological model of prostate cancer cells, one realizes that there is a potential theoretical advantage to delivering a greater biological effective dose per treatment in a lower number of fractions. Both recent and older publications have attempted to explore this treatment option. This critical review comprehensively examines the current state of knowledge concerning hypofractionated radiotherapy in prostate cancer.

Intra-Parenchymal Mesenchymal Chondrosarcoma of the Cerebellum: Case Report and Review of the Literature

SummaryA 44-year-old male presented with a 3-week history of clumsiness and numbness of the left hemibody. CT scan and MRI revealed a 2 cm mass in the right hemisphere of the cerebellum. The patient underwent a sub-occipital craniotomy with gross total resection of the intra-parenchymal lesion. On pathology, the lesion was found to be compatible with a mesenchymal chondrosarcoma. The patient received adjuvant radiation treatment and remains free of disease 60 months after completion of treatment. Mesenchymal chondrosarcomas are neoplasms that rarely arise intra-cranially. Thirty cases have been found in the literature. Our case resembles more closely six of these cases because the tumour had no dural attachment. We describe our case in more detail and review similar cases found in the English literature.

Partial kilovoltage cone beam computed tomography, complete kilovoltage cone beam computed tomography, and electronic portal images for breast radiation therapy: A dose-comparison study

PURPOSE The purpose of this study was to compare absorbed dose with the treated breast and organs at risks (OARs) with weekly image guidance using electronic portal imaging (EPI), complete kilovoltage cone beam computed tomography (kV CBCT), and partial kV CBCT. METHODS AND MATERIALS Using a thorax female phantom, we determined absorbed doses to treated and contralateral breast, ipsilateral and contralateral lung, heart, and skin for tangential EPI, complete kV CBCT, and partial kV CBCT. Doses were measured by use of ionization chambers and compared with treatment planning system calculations. With simulation of breast tangential irradiation to a standard dose of 50 Gy in 25 fractions, dose to each organ was measured for each image guidance technique. RESULTS Use of weekly EPI was associated with a significantly increased dose to the treated breast compared with weekly complete and partial kV CBCT (4.44 ± 0.04 vs 1.00 ± 0.07 vs 0.576 ± 0.003 cGy, respectively). Dose to the contralateral breast, ipsilateral and contralateral lung, heart, and contralateral skin was lower with EPI than with either complete or partial kV CBCT (0.042 ± 0.004 vs 0.36 ± 0.01 vs 0.23 ± 0.01 cGy, 0.06 ± 0.04 vs 0.42 ± 0.02 vs 0.31 ± 0.01 cGy, 0.004 ± 0.002 vs 0.29 ± 0.01 vs 0.22 ± 0.01 cGy, 0.03 ± 0.08 vs 0.36 ± 0.02 vs 0.25 ± 0.01 cGy, and 0.20 ± 0.02 vs 0.80 ± 0.06 vs 0.40 ± 0.03 cGy, respectively). Compared with complete CBCT, the use of partial CBCT allowed dose reductions of 42%, 37%, 27%, 24%, and 28% to the ipsilateral breast, contralateral breast, ipsilateral lung, contralateral lung, and heart, respectively. Additional dose from weekly CBCT was significantly lower than treatment-related scatter dose for all OARs. CONCLUSIONS Use of CBCT was associated with decreased dose to ipsilateral breast and increased dose to all OARs compared with EPI. Significant dose reduction can be achieved with the use of partial CBCT, while generally maintaining image quality.

Hypofractionation for prostate cancer: an update

ABSTRACT 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/β 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.

Prostate cancer and androgenic alopecia

Prostate cancer is a burden on society. Its prevalence can reach up to 80% in males aged 70 years and older. Current screening programs based on prostate-specific antigen testing lead to overdiagnosis and overtreatment with uncertain benefits on survival. Androgenic alopecia is also highly prevalent in elderly males. Observational studies have found that androgenic alopecia is linked to prostate cancer, but studies have been conflictual. Further research should focus on finding the exact mechanism linking these two pathologies. This should help clinicians improve screening programs and guide research into novel molecules to help in the prevention and treatment of both androgenic alopecia and prostate cancer.