D. Nguyen

Can Locoregional Treatment of the Primary Tumor Improve Outcomes for Women With Stage IV Breast Cancer at Diagnosis

PURPOSE To examine the effect of locoregional treatment (LRT) of the primary tumor on survival in patients with Stage IV breast cancer at diagnosis. METHODS AND MATERIALS The study cohort comprised 733 women referred to the British Columbia Cancer Agency between 1996 and 2005 with newly diagnosed clinical or pathologic M1 breast cancer. Tumor and treatment characteristics, overall survival (OS), and locoregional progression-free survival were compared between patients treated with (n = 378) and without (n = 355) LRT of the primary disease. Multivariable analysis was performed with Cox regression modeling. RESULTS The median follow-up time was 1.9 years. LRT consisted of surgery alone in 67% of patients, radiotherapy alone in 22%, and both in 11%. LRT was used more commonly in women with age <50 years, Eastern Cooperative Oncology Group (ECOG) performance status 0-1, Stage T1-2 tumors, N0-1 disease, limited M1 burden, and asymptomatic M1 disease (all p < 0.05). Systemic therapy was used in 92% of patients who underwent LRT and 85% of patients who did not. In patients treated with LRT compared with those without LRT, the 5-year OS rates were 21% vs. 14% (p < 0.001), and the rates of locoregional progression-free survival were 72% vs. 46% (p < 0.001). Among 378 patients treated with LRT, the rates of 5-year OS were higher in patients with age <50, ECOG performance status 0-1, estrogen receptor-positive disease, clear surgical margins, single subsite, bone-only metastasis, and one to four metastatic lesions (all p < 0.003). On multivariable analysis, LRT was associated with improved OS (hazard ratio, 0.78; 95% confidence interval, 0.64-0.94, p = 0.009). CONCLUSION Locoregional treatment of the primary disease is associated with improved survival in some women with Stage IV breast cancer at diagnosis. Among those treated with LRT, the most favorable rates of survival were observed in subsets with young age, good performance status, estrogen receptor-positive disease, clear margins, and distant disease limited to one subsite, bone-only involvement, or fewer than five metastatic lesions.

Simultaneous Integrated Boost Using Intensity-Modulated Radiotherapy Compared With Conventional Radiotherapy in Patients Treated With Concurrent Carboplatin and 5-Fluorouracil for Locally Advanced Oropharyngeal Carcinoma

PURPOSE To compare, in a retrospective study, the toxicity and efficacy of simultaneous integrated boost using intensity-modulated radiotherapy (IMRT) vs. conventional radiotherapy (CRT) in patients treated with concomitant carboplatin and 5-fluorouracil for locally advanced oropharyngeal cancer. METHODS AND MATERIALS Between January 2000 and December 2007, 249 patients were treated with definitive chemoradiation. One hundred patients had 70 Gy in 33 fractions using IMRT, and 149 received CRT at 70 Gy in 35 fractions. Overall survival, disease-free survival, and locoregional control were estimated using the Kaplan-Meier method. RESULTS Median follow-up was 42 months. Three-year actuarial rates for locoregional control, disease-free survival, and overall survival were 95.1% vs. 84.4% (p = 0.005), 85.3% vs. 69.3% (p = 0.001), and 92.1% vs. 75.2% (p < 0.001) for IMRT and CRT, respectively. The benefit of the radiotherapy regimen on outcomes was also observed with a Cox multivariate analysis. Intensity-modulated radiotherapy was associated with less acute dermatitis and less xerostomia at 6, 12, 24, and 36 months. CONCLUSIONS This study suggests that simultaneous integrated boost using IMRT is associated with favorable locoregional control and survival rates with less xerostomia and acute dermatitis than CRT when both are given concurrently with chemotherapy.

Toxicity report of once weekly radiation therapy for low-risk prostate adenocarcinoma: preliminary results of a phase I/II trial.

BackgroundIncreasing clinical data supports a low α/β ratio for prostate adenocarcinoma, potentially lower than that of surrounding normal tissues. A hypofractionated, weekly radiation therapy (RT) schedule should result in improved tumour control, reduced acute toxicity, and similar or decreased late effects. We report the toxicity profile of such treatment.Materials and MethodsWe conducted a multi-institution phase I/II trial of three-dimensional conformal radiation therapy (3D-CRT) for favourable-risk prostate cancer (T1a-T2a, Gleason ≤ 6 and PSA < 10 ng/ml). RT consisted of 45 Gy in nine 5 Gy fractions, once weekly. Primary end-points were feasibility and late gastrointestinal (GI) toxicity (RTOG scale), while secondary end-points included acute GI toxicity, acute and late genitourinary (GU) toxicity, biochemical control, and survival.ResultsBetween 2006 and 2008, 80 patients were treated. No treatment interruptions occurred. The median follow-up is 33 months (range: 20-51). Maximal grade 1, 2, and 3 acute (< 3 months) GU toxicity was 29%, 31% and 5% respectively (no grade 4). Acute GI grade 1 toxicity was reported in 30% while grade 2 occurred in 14% (no grade 3 or 4). Crude late grade ≥ 3 toxicity rates at 31 months were 2% for both GU and GI toxicity. Cumulative late grade ≥ 3 GI toxicity at 3 years was 11%. Two patients had PSA failure according to the Phoenix definition. The three-year actuarial biochemical control rate is 97%.ConclusionsWeekly RT with 45 Gy in 9 fractions is feasible and results in comparable toxicity. Long term tumour control and survival remain to be assessed.

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.

Population-based Analysis of Treatment and Survival in Women Presenting With Brain Metastasis at Initial Breast Cancer Diagnosis.

Purpose:Brain metastasis at initial breast cancer diagnosis is rare. This study aims to evaluate the clinical characteristics of these patients and identify prognostic and treatment factors associated with improved survival. Methods:Subjects were 35 women referred from 1996 to 2005 with newly diagnosed breast cancer with synchronous brain metastasis. Overall survival (OS) and brain progression-free survival were examined using Kaplan-Meier methods and compared between subgroups with different clinicopathologic and treatment characteristics using log-rank tests. Results:Median age was 65 years. Whole-brain radiotherapy (WBRT) alone was used in 25 patients, surgical resection and postoperative WBRT in 5 patients, and no or unknown treatment in 5 patients. Patients who underwent cranial resection were more likely to have solitary brain metastasis (P=0.003) and no visceral involvement (P=0.006). Overall, median OS was 6.8 months and median brain progression-free survival was 6.5 months (range, 0.7 to 54 mo). Median OS were 15 months with surgery and postoperative WBRT, 5 months with WBRT alone, and 3 months with no brain treatment. Longer OS was observed with age below 65 years versus 65 years and above (11 vs. 5 mo, P=0.046), 0 to 1 versus ≥2 sites of extracranial metastasis (10 vs. 3 mo, P=0.047), and diagnosis from 2001 to 2005 versus 1996 to 2000 (10 vs. 3 mo, P=0.018). A trend toward improved OS was observed in patients with no visceral involvement (11 vs. 4 mo, P=0.09). Conclusions:In this unique cohort presenting with breast cancer and synchronous brain metastasis, longer survival were observed with young age, limited extracranial metastasis, and no visceral disease. These characteristics may be used to select candidates for more aggressive treatment.

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.