Early salvage radiation therapy combined with short-term hormonal therapy in recurrent prostate cancer after radical prostatectomy: single-institution 4-year data on outcome, toxicity, health-related quality of life and co-morbidities from 184 consecutive patients treated with 70 Gy.

The aim of this study was to investigate the role of 70 Gy salvage radiotherapy (SRT) combined with short-term neoadjuvant hormonal therapy (NHT) in the treatment of recurrent disease after radical prostatectomy (RP), and to consider quality of life (QoL), survival outcomes and impact of co-morbidities on treatment-related rectal-genitourinary toxicity. Electronic records of 184 SRT patients treated consecutively between October 2001 and February 2007 were analyzed. Median age was 64 years (median follow-up 48 months). NHT was given to 165 patients (median 3 months). Pre-RP and pre-SRT PSA, PSA doubling time, Gleason score (GS), seminal vesicle invasion (SVI) and detectable post-SRT PSA were recorded. Any detectable PSA or PSA >0.1 ng/ml + nadir was considered biochemical failure (BcF). The Charlson co-morbidity index was used to correlate co-morbidities and rectal-genitourinary toxicity. Scores from the health-related QoL EORTC QLQ-C30 and PR-25 questionnaires were also evaluated. In 116 (63%) patients, a long-lasting curative effect was indicated by undetectable PSA levels. In univariate analysis, using BcF as an outcome variable, p<0.001 was found for GS, pre-SRT PSA, SVI and detectable post-SRT PSA. Multivariate analysis showed p=0.01 for SVI, p=0.09 for GS, and detectable post-SRT PSA (p=0.01); with metastases as an outcome variable, only SVI was significant (p=0.007). Cancer-specific and overall survival were 99 and 95%, respectively. Although microscopy showed SVI or GS 8-10 in the prostatectomy specimens 17/40 (43%) and 13/29 (45%), respectively, of patients still showed undetectable PSA at long-term follow-up (median 55 months) after SRT. Likewise, 11/31 (36%) patients with pre-SRT PSA >1.0 ng/ml and 80/134 (60%) patients with PSA doubling time (PSADT) <10 still showed undetectable PSA after 50 months. Slightly elevated acute and late rectal-genitourinary grade 3-4 toxicity was observed. No association with co-morbidity/toxicity was found. EORTC QLQ-C30 scores were similar to or slightly better than reference values. SRT with 70 Gy combined with 3-month NHT results in long-term undetectable PSA in >50% of patients with recurrence after RP with acceptable rectal-genitourinary toxicity and without negatively affecting long-term QoL. Non-metastatic patients should not be disqualified from receiving SRT although presenting with poor prognostic factors at surgery.

Radiation-induced vascular damage in tumors: implications of vascular damage in ablative hypofractionated radiotherapy (SBRT and SRS).

We have reviewed the studies on radiation-induced vascular changes in human and experimental tumors reported in the last several decades. Although the reported results are inconsistent, they can be generalized as follows. In the human tumors treated with conventional fractionated radiotherapy, the morphological and functional status of the vasculature is preserved, if not improved, during the early part of a treatment course and then decreases toward the end of treatment. Irradiation of human tumor xenografts or rodent tumors with 5-10 Gy in a single dose causes relatively mild vascular damages, but increasing the radiation dose to higher than 10 Gy/fraction induces severe vascular damage resulting in reduced blood perfusion. Little is known about the vascular changes in human tumors treated with high-dose hypofractionated radiation such as stereotactic body radiotherapy (SBRT) or stereotactic radiosurgery (SRS). However, the results for experimental tumors strongly indicate that SBRT or SRS of human tumors with doses higher than about 10 Gy/fraction is likely to induce considerable vascular damages and thereby damages the intratumor microenvironment, leading to indirect tumor cell death. Vascular damage may play an important role in the response of human tumors to high-dose hypofractionated SBRT or SRS.

Curative stereotactic body radiotherapy for liver malignancy.

Nine patients with 11 primary or secondary liver non-neuroendocrine malignancies with mean and maximum diameters of 4.0 and 7.7 cm became long-term survivors after precision irradiation in a stereotactic body frame. Doses varied from 20 to 45 Gy split at 2-4 occasions a few days apart, with higher doses in the target centers. Occasional chemotherapy was stopped well before irradiation. No hospitalizations were needed because side effects, regional pain and nausea, were mild. All patients have now survived 5-14 years without recurrences. Two verified and one suspected secondary cancers occurred in organs close to the irradiated targets, and two of them could be resected for cure. Precision irradiation can thus cure selected liver malignancies. It is the first non-invasive method to achieve this, and the present patients are its first long-term survivors. A prolonged follow-up period is, however, necessary, because we have in other patients seen local tumor regrowth as late as four years after irradiation. The approach may cure some tumors, which are technically unsuited for other treatment modalities, and can be used for patients at high surgical risk. The success rate for local control seems good, but has to be defined by formal studies after optimization of radiation doses.

Evidence-based medicine: its effect on treatment recommendations as illustrated by the changing role of postmastectomy irradiation to treat breast cancer.

PURPOSE: To illustrate the effect that the quality of evidence has on clinical practice, we examined how the role of radiotherapy in treating breast cancer has changed over the years as the quality of evidence evolved from anecdotal evidence based on expert opinion to randomized clinical trials and meta-analyses. METHODS: We searched the medical literature for key randomized studies and meta-analyses that have influenced the clinical use of postmastectomy irradiation since the first randomized trials in breast cancer in the 1950s. We discuss how clinical practice changed based on the outcomes of these trials, and then discuss the quality of those trials based on the criteria currently used to assess evidence from randomized trials (CONSORT) and meta-analysis (QUORUM). RESULTS: Evidence published from the early trials and meta-analyses on the role of postmastectomy irradiation had a strong effect on clinical practice. Examination of these studies, however, continues to show significant flaws in trial design that, by today's evidence-based standards, would not meet standards of quality. CONCLUSION: The quality of evidence has a strong effect on shaping clinical practice and needs to be continually assessed. Current guidelines developed to critique both individual randomized trials and meta-analyses are helping to establish high standards for trial design and interpretation. Evidence from older trials that were not guided by well-developed guidelines need to be reviewed, particularly when results from those trials are continually updated and used to generate evidence on which to base current clinical practice.