Association between acute histopathological changes of rectal walls and late radiation proctitis following radiotherapy for prostate cancer.

PURPOSE: The impact of acute histopathological changes (HC) of the rectum on development of late clinical proctitis (LCP) after external radiotherapy (RT) for prostate cancer is poorly explored and was the primary end point of this prospective study. METHODS: In 70 patients, 15 HC of early rectal biopsies after RT were identified, whereby RT was conventional 2D RT in 41 cases and conformational 3D RT in 29. Associations of HC in anterior and posterior rectal walls (ARW, PRW) with LCP, acute endoscopic (AEP) and acute clinical proctitis (ACP) were statistically evaluated considering as explicative variables the patient general characteristics and the HC. RESULTS: The mean patients' follow-up was 123.5 months (24-209). The median prostatic dose was 72 Gy (2 Gy/fraction). For the 41 and 29 patients the ARW and PRW doses were 64 and 49 Gy vs. 63 and 50 Gy, respectively. The incidence of LCP ≥ grade 2 at 10 years was 12.9%. The univariate (p = 0.02) and Kaplan-Meyer methods (p = 0.007) showed that the gland (or crypts) loss in the ARW was significantly associated with LCP. AEP and ACP occurred in 14.3 and 55.7% of cases. At multivariate level AEP significantly correlated with hemorrhoids (p = 0.014) and neutrophilia in ARW (p = 0.042). CONCLUSIONS: Early after RT, substantial gland loss in ARW is predictive of LCP. To reduce this complication with conventional fractionation, we suggest keeping the mean dose to ARW ≤48-52 Gy.

How iliopelvic lymphoscintigraphy can affect the definition of planning target volume in radiation therapy of pelvic and testicular tumors.

PURPOSE: External beam radiation therapy (EBRT) of most intrapelvic and testicular tumors has been generally performed with large fields encompassing both the primary disease and lymphatic drainage. This study was carried out to map the pelvic and periaortic lymphatics by means of iliopelvic lymphoscintigraphy (IPL) in preparation for radiotherapy planning. METHODS AND MATERIALS: Between January 2000 and October 2001, 70 patients scheduled for EBRT (61 operated on, 52 females, 18 males, mean age 61, range, 24-80), affected with uterine (43), rectal (11), testicular (8), anal (4), penile (2), and vulvar (2) cancers were enrolled in the study. IPL was performed by injection of 99mtechnetium-nanocolloids in the bipedal (70 cases) or bipedal plus perianal (20 cases) sites. The sensitivity of IPL in mapping the lymphatic anatomy was evaluated first. Then three radiation oncologists scored the modifications induced by IPL on the planning target volume (PTV) which had been previously delineated only on the basis of bony landmarks. The original fields were classified "inadequate" if they failed to match the new PTV by more than 1 cm. RESULTS: IPL sensitivity in showing the inguinal, external iliac, common, and periaortic lymphatics was 100%, 90%, 80%, and 70% in anterior-posterior (A-P) projections, and 100%, 80%, 70%, and 60% in lateral projections respectively. For the presacral and hypogastric ones the sensitivity was 40%. When compared with bony landmarks, IPL changed the delineation of PTV in 24 of 70 A-P P-A fields (34%) and 22 of 58 (38%) lateral fields. Furthermore, 8/12 (67%) lymphadenectomies resulted in being incomplete. No IPL-related toxicity was observed. CONCLUSION: IPL is a safe, inexpensive (cost: 100 Euros), and effective method to map the lymphatic chains. In the A-P scintigrams these structures were detected in 85% (70-100%) of the patients referred for total pelvis irradiation, and this figure could be higher in subjects not operated on. IPL can also give a reliable evaluation of the lymphadenectomies in order to schedule the proper treatments after surgery. Finally, IPL may change the conventional PTV for pelvic irradiation in about 36% (34-38%) of the cases; therefore, the fields should be tailored more around the lymphatic landmarks than the bony landmarks.

Salvage therapy of small volume prostate cancer nodal failures: a review of the literature.

New imaging modalities may be useful to identify prostate cancer patients with small volume, limited nodal relapse ("oligo-recurrent") potentially amenable to local treatments (radiotherapy, surgery) with the aim of long-term control of the disease, even in a condition traditionally considered prognostically unfavorable. This report reviews the new diagnostic tools and the main published data about the role of surgery and radiation therapy in this particular subgroup of patients.

Role of early proctoscopy in predicting late symptomatic proctitis after external radiation therapy for prostate carcinoma.

PURPOSE: To determine whether acute radiation-proctitis, diagnosed by proctoscopy after radiation therapy for prostate cancer, can predict late clinical proctitis. METHODS AND MATERIALS: A prospective study of 130 patients who underwent external radiation therapy (RT) for stage T1 to T4 prostate cancer between 1997 and 2008 was performed. Treatments were conventional (2-dimensional [2D]) in 61 patients and 3D conformal in 69, with a median target dose of 72 Gy (70-74 Gy). Within 1 week after RT, proctoscopy was performed to detect possible acute endoscopic proctitis (AEP). Acute clinical proctitis (ACP) and late clinical proctitis (LCP) were also evaluated. The median follow-up was 84 months (20-180 months). The influence of AEP and ACP on LCP occurrence was studied using the Cox model controlling for age, dose, prostatectomy, RT technique (2D vs 3D), and hormone therapy. RESULTS: AEP was detected in 15 patients (11.5%) and ACP in 67 (51.5%); in 13 cases (10%) AEP and ACP occurred simultaneously. Thirty-five cases of LCP were recorded. The 5-year probability of developing LCP was highest in patients with AEP and ACP (77%, 95% confidence interval [CI] 53%-94%) and lowest in asymptomatic patients (14%, 95% CI 7%-26%; P<.001). Compared to asymptomatic patients, the 5-year probability also was slightly increased in patients with ACP only (26%, 95% CI 16%-40%; P=.052). In multivariable analysis, the combination of AEP and ACP was the main predictor of LCP: compared to asymptomatic patients, the hazard ratio was 5.6 (2.1-15.2) in patients with AEP plus ACP (P=.001) and 2.1 (0.9-4.9) in those with ACP only (P=.103). CONCLUSIONS: In patients with AEP and ACP, the risk of LCP was more than 5-fold increased compared to those who were asymptomatic, while a much smaller increase in risk occurred in patients with ACP only. Early proctoscopy can provide valuable information regarding the likelihood of late proctitis.

Salvage therapy of intraprostatic failure after radical external-beam radiotherapy for prostate cancer: a review.

Radical external-beam radiotherapy (EBRT) is a standard treatment for prostate cancer (PC) patients. Despite this, the rate of intraprostatic relapses after primary EBRT is still not negligible. There is no consensus on the most appropriate management of these patients after EBRT failure. Treatment strategies after PC relapse are strongly influenced by the effective site of the tumor recurrence, and thus the instrumental evaluation with different imaging techniques becomes crucial. In cases of demonstrated intraprostatic failure, several systemic (androgen deprivation therapy) or local (salvage prostatectomy, cryotherapy, high-intensity focused ultrasound, brachytherapy, stereotactic EBRT) treatment options could be proposed and are currently delivered by clinicians with a variety of results. In this review we analyze the correct definition of intraprostatic relapse after radiotherapy, focusing on the recent developments in imaging to detect intraprostatic recurrence. Furthermore, all available salvage treatment options after a radiation therapy local failure are presented and thoroughly discussed.

Double-flash, large-fraction radiation therapy as palliative treatment of malignant superior vena cava syndrome in the elderly.

Rapid control of symptoms is mandatory in cancer-induced superior vena cava syndrome (SVCS), but older patients often do not tolerate aggressive approaches. In order to maximize symptom relief and minimize treatment-related discomfort of aged patients in poor health we adopted a short-course, large-fraction radiation therapy (RT) schedule. Twenty-three consecutive patients aged over 70 who were suffering from solid-malignancy-related SVCS were enrolled. A total dose of 12 Gy was given in two 6-Gy fractions, 1 week apart, mainly in an out-patient setting. Completion of therapy to give up to 37-40 Gy was planned in the best-responding patients. Symptom relief was experienced by 8 patients as early as 4-5 days after the first fraction. The overall response rate was 87%. Despite some mild systemic side effects (chest pain, fever) reported by 5 patients (22%), overall toxicity was negligible. Short-course, double-flash RT stands as an effective and safe tool in the palliative treatment of malignant SVCS in older patients. Fractions larger than 6 Gy can be avoided in order to minimize side and toxic effects.