•IMRT plans optimized with the RTOG0415 criteria showed similar results with CRT.•General constraints are not suitable for optimally sparing the rectum using IMRT.•Treatment plans with higher quality ...(lower NTCP for the same TCP) showed higher risk for secondary cancer.•Treatment plan optimization should be complemented with the risks for secondary cancer.
The purpose of this study is to evaluate the clinical efficacy of both step-and-shoot IMRT and 3D-Conformal Radiation Therapy modalities (CRT) in treating prostate cancer using radiobiological measures. Another aim was to estimate the risks for developing secondary malignancies in bladder and rectum due to radiotherapy from the corresponding modalities. The treatment plans of ten prostate cancer patients were developed using IMRT and CRT. For the IMRT plans, two beam energies and two treatment protocols were used (the RTOG 0415 and a most restrictive one proposed by Fox Chase Cancer Center (FCCC)). For the evaluation of these plans, the complication-free tumor control probability, the total probability of injury, the total probability of control/benefit, and the biologically effective uniform dose were employed. Furthermore, based on the dosimetric data of IMRT and CRT, the risk for secondary malignancies was calculated for bladder and rectum. The average risk for secondary malignancy was lower for the bladder (0.37%) compared to the rectum (0.81%) based on all the treatment plans of the ten prostate cancer patients. The highest average risk for secondary malignancy for bladder and rectum was for the CRT-6X modality (0.46% and 1.12%, respectively) and the lowest was for the IMRT RTOG-18X modality (0.33% and 0.56%, respectively). The ≥ Grade 2 LENT/SOMA response probability was lower for the bladder than for the rectum in all the plans. For the bladder the highest average value was for the IMRT RTOG-18X (0.9%) and the lowest was for the CRT-18X modality (0.1%). For the rectum, the highest average value was for the IMRT RTOG-6X (11.9%) and the lowest was for the IMRT FCCC-18X modality (2.2%). By using radiobiological measures it is shown that the IMRT FCCC plans had the lowest risks for normal tissue complications, whereas the IMRT RTOG had the highest. Regarding the risk for secondary malignancies, the CRT plans showed the highest values for both bladder and rectum.
Introduction
Patients have increasing longevity and time for bone healing following radiotherapy (RT) for treatment of bone metastases (BM). Attempts to assess the treatment response of bone ...metastases have been either limited or heavily subjective. Our goal was to try to quantitate cancer-involved bone changes after RT using changes in bone mineral density (BMD) from computer tomographic (CT) imaging.
Methods
Retrospectively, 117 spinal metastases were identified that received RT with follow-up CT scans >9 months following CT simulation. Contoured volumes included: the metastasis (gross tumor volume; GTV); the involved vertebra (gross bone volume; GBV); a total lytic volume (Lyt); a dominant lytic volume (Domlyt); a control volume, and the nearest uninvolved, unirradiated vertebra (control bone volume; CBV). The Hounsfield-density calibration curve was used to measure the density of these volumes before and after treatment.
Results
Whether using raw or control-adjusted changes, the absolute and percent change in density of the GBV, GTV, Lyt, and Domlyt volumes all significantly increased (each p<0.0001). The increase in the density of Domlyt volumes was greater than that of Lyt volumes (p=0.0465), which were greater than GTV (p=0.0065), which were greater than GBV (p<0.0001). On multivariate analysis, only the biologically effective dose (BED) dose significantly correlated with GTV density change (p=0.0175). K means clustering created groups by initial lesion size, GTV, or GBV density. A significant difference in GTV density change was not detected between any groups.
Conclusion
Increases in BMD are associated with healing regardless of lesion size or initial density. A prospective study to determine whether long-term control is related to early density measurements is needed.
Hypofractionated radiotherapy (HRT) would be more convenient for men with low-risk prostate cancer and cost less than conventional radiotherapy (CRT) as long as HRT is noninferior to CRT in terms of ...survival and quality of life (QOL) is not found to be worse.
To assess differences in QOL between men with low-risk prostate cancer who are treated with HRT vs CRT.
In this phase 3 randomized clinical trial, men with low-risk prostate cancer were enrolled from sites within the National Cancer Institute's National Clinical Trials Network in the United States, Canada, and Switzerland.
Random assignment to CRT (73.8 Gy in 41 fractions over 8.2 weeks) or to HRT (70 Gy in 28 fractions over 5.6 weeks).
Quality of life was assessed using the Expanded Prostate Index Composite questionnaire measuring bowel, urinary, sexual, and hormonal domains; the 25-item Hopkins Symptom Checklist measuring anxiety and depression; and the EuroQol-5 Dimension questionnaire measuring global QOL. All data were collected at baseline and 6, 12, 24, and 60 months. Change scores were compared between treatment arms using the Wilcoxon signed rank test. A significance level of .0125 to adjust for multiple comparisons was used for an overall 2-sided type 1 error of .05. Clinical significance was determined for the Expanded Prostate Index Composite change scores by an effect size of 0.5.
Of 1092 patients analyzable for the primary end point, 962 (mean SD age, 66.6 7.4 years) consented to the QOL component. No statistically significant differences with regard to baseline characteristics nor any of the QOL baseline domains were measured between arms. There were no differences in change score between arms with respect to any of the Expanded Prostate Index Composite questionnaire domain scores except at 12 months when the HRT arm had a larger decline than the CRT arm in the bowel domain (mean score, -7.5 vs -3.7, respectively; P<.001), but it did not reach clinical significance (effect size = 0.29). There were no differences between arms at any time point for the Hopkins Symptom Checklist nor EuroQol-5 Dimension questionnaire.
Treatment with HRT is noninferior to CRT in men with low-risk prostate cancer in terms of disease-free survival and, as shown in the present study, in prostate cancer-specific (eg, bowel, bladder, sexual) and general QOL, as well as in anxiety and depression. This study provides evidence to affirm that HRT is a practice standard for men with low-risk prostate cancer.
ClinicalTrials.gov identifier: NCT00331773.
In early surgical series, the incidence of positive lymph nodes in patients with prostate cancer was approximately 40%. In the modern era of screening and improved patient selection, the incidence is ...now <10%, although most series excluded patients with higher risk disease. The risk of having positive lymph nodes is influenced by disease stage, prostate-specific antigen level, and tumor grade and by the aggressiveness of lymph node dissection. Many of the same factors predict the outcome of these patients. Although the percentage of patients with positive lymph nodes has declined, there remain significant numbers of patients with lymph node-positive prostate cancer, and it remains a therapeutic dilemma.
Abstract Objectives To investigate the oncologic influence of transurethral resection of the prostate (TURP) as a cytoreductive surgery in metastatic hormone sensitive prostate cancer (mHSPC), in the ...setting of continuous complete androgen blockade (CAB). Materials and methods Medical histories of 146 consecutive Chinese males with newly diagnosed mHSPC, registered in our institution in 2006 and 2007, were reviewed. All of these patients received CAB as initial systematic therapy. Demographics and cancer control outcomes from 39 mHSPC patients who underwent TURP for a relief of bladder outlet obstruction were compared with those of the other 107 who received CAB only when they were still hormone-sensitive. Median follow-up was 15 months (3 to 27 months). Results Age at diagnosis, baseline PSA, and biopsy Gleason score were comparable between the 2 groups. Patients who underwent a TURP had lower PSA nadir (median 0.15 ng/ml vs. 0.82 ng/ml, P = 0.015) and longer time to PSA nadir (11.2 months vs. 6.4 months, P < 0.001). More patients in the non-TURP group developed hormone refractory prostate cancer ( P = 0.007). The TURP group had a tendency towards longer disease-specific survival and overall survival (24.4 months vs. 24.1 months and 24.4 months vs. 22.9 months, respectively), though this did not reach statistical significance. Conclusions TURP resulted in a better and more prolonged response to hormone therapy in mHSPC, with a trend towards positive influence in disease specific survival and overall survival. To date, our preliminary report is the first study regarding long-term survival of cytoreductive surgery in mHSPC, and further investigations are warranted.
The results of salvage radiation therapy for rising prostate-specific antigen (PSA) levels after radical prostatectomy appear favorable, but the ultimate outcome is uncertain, given the relatively ...short follow-up in most studies. We report on a group of patients at a median follow-up of 13.9 years after salvage radiation therapy.
From 1990 to 1995, 92 patients were referred postoperatively for radiation for a rising PSA level. PSA level at the time of referral ranged from 0.1 to 30.5 ng/ml (median, 1.5 ng/ml). The median time from surgery to radiation was 2.1 years (range,, 0.3-7.4 years). Radiation was directed to the prostatic fossa only with a median dose of 6,500 cGy (range, 6,000-7,000 cGy).
Eighty-five patients experienced a PSA drop after radiation, as predicted by Gleason score and PSA level at the start of radiation. Five- and 10-year biochemical failure free survival (BFFS) was 35% and 26%, respectively, and overall survival was 86% and 67%, respectively. Median survival was 12.0 years, and median BFF was 2.3 years. The presurgery PSA level was not predictive, but the PSA level at the start of radiation predicted a response. Patients with Gleason 8 to 9 cancers had a significantly higher progression rate than those with lower Gleason scores. There were no significant differences in outcomes based on pathology findings (none vs. positive margins vs. positive seminal vesicles). Overall, 22 (24%) patients died directly from prostate cancer, resulting in a 10-year cancer-specific survival rate of 82%. Multivariate analysis risk factors for dying of cancer were Gleason's score (8 to 9) and PSA at the start of radiation therapy (>1.0 ng/ml).
Patients have a good response to salvage radiation therapy. A small but durable subgroup appears to have permanent control. In those for whom therapy fails, radiation delays the need for other salvage therapy, indicating at least a transient benefit to most patients.
Chemo-radiation is a well-established alternative to radical cystectomy in patients with muscle-invasive bladder cancer. Many patients due to age or medical comorbidity are unfit for either radical ...cystectomy, or standard cisplatin- or 5-fluorouracil-based chemoradiation, and do not receive appropriate treatment with curative intent. We treated patients with a less aggressive protocol employing seven weekly doses of paclitaxel and daily irradiation. In those whose tumors showed overexpression of her2/neu, seven weekly doses of trastuzumab were also administered.
To report the long-term survival outcomes and toxicity results of the of NRG Oncology RTOG 0524 study.
Seventy patients were enrolled and 65 (median age: 76 yr) were deemed eligible. Patients were assigned to daily radiation and weekly paclitaxel + trastuzumab (group 1, 20 patients) or to daily radiation plus weekly paclitaxel (group 2, 45 patients) based on tumor her2/neu overexpression. Radiation was delivered in 1.8 Gy fractions to a total dose of 64.8 Gy.
The primary endpoint was unresolved treatment-related toxicity. The secondary endpoints were complete response rate, protocol completion rate, and disease-free and overall survival.
Protocol therapy was completed by 60% (group 1) and 76% (group 2); complete response rates at 12 wk were 62% in each group. Acute treatment-related adverse events (AEs) of grade ≥3 were observed in 80% in group 1 and 58% in group 2. There was one treatment-related grade 5 AE in group 1. Unresolved acute treatment-related toxicity was 35% in group 1 and 31% in group 2. The median follow-up was 2.3 yr in all patients and 7.2 yr in surviving patients. Overall survival at 5 yr was 25.0% in group 1 and 37.8% in group 2 (33.8% overall). At 5 yr, disease-free survival was 15.0% in group 1 and 31.1% in group 2.
In a cohort of patients with muscle-invasive bladder cancer who are not candidates for cystectomy or cisplatin chemotherapy, chemoradiation therapy offers a treatment with a significant response rate and 34% 5-yr overall survival. While there were many AEs in this medically fragile group, there were few grade 4 events and one grade 5 event attributable to therapy.
Patients with invasive bladder cancer who cannot tolerate surgery were treated with radiation and systemic therapy without surgically removing their bladders. Most patients tolerated the treatment, were able to keep their bladders, and showed a significant treatment response rate.
A review was conducted of divergent-risk prostate cancer patients treated with radiation. These patients exhibited a low-volume, low-risk Gleason score but high-risk prostate-specific antigen level. ...The clinical outcomes were compared with those of classically high-risk and ultra-low risk patients. The disease prognosis of the divergent-risk group was equally poor as their classically high-risk counterparts. These patients should be treated similarly to classically high-risk patients.
Rarely, patients with prostate cancer present with prostate-specific antigen (PSA) scores > 20 ng/mL but with otherwise very-low-risk disease. Oncologists have debated whether the malignancies in these patients behave more comparably to low-risk or high-risk disease. Our objective was to elucidate the behavior of these malignancies.
A retrospective review was conducted of prostate cancer patients treated with radiation from 2000 to 2013. The inclusion criteria for very-low-risk disease included stage T1a-T1c, Gleason score ≤ 6, ≤ 3 positive cores, ≤ 50% involvement of any core, and PSA level < 10 ng/mL. The divergent-risk group met all the same criteria but had a PSA score of 20 to 80 ng/mL. The high-grade, low-volume group consisted of patients with stage T1c-T2a, PSA level < 20 ng/mL, Gleason score of 4+4, and < 4 positive cores. Treatment failure was defined as a PSA nadir plus 2 ng/mL.
A total of 18, 60, and 19 patients were in the divergent, low-risk, and high-grade groups, respectively. Biochemical progression-free survival at 5 years was 71.3% for the divergent group, 68.8% for the high-grade group, and 98.3% for the low-risk group. The biochemical failure rate for the divergent group differed significantly from the low-risk group (P = .021), and that for the low-risk group was significantly different from that of the high-grade group (P = .025). However, the divergent group did not appear different from the high-grade group (P = .53).
The results of our study have shown that the disease prognosis for the divergent-risk group is worse than that for the very-low-risk disease group and does not appear to be different from that for the low-volume, high-grade disease group. Oncologists should be aware that the outcomes for divergent patients are similarly poor to their low-volume, classically high-risk counterparts.
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