Radiotherapy For Prostate Carcinoma Research Articles

Radiation induced lichen planus - an uncommon side effect

Cutaneous lichen planus is classically characterized by violaceous, pruritic, planar papules and plaques, most commonly affecting the extremities. Lichen planus following radiation therapy is extremely rare and lichen planus following radiation therapy for prostate carcinoma has not been previously reported in the literature. We report a 66-year-old man who presented to the dermatology clinic with a symmetric pruritic eruption affecting the pelvic and gluteal region within two months of radiation therapy targeting the prostate and pelvic lymph nodes for prostate adenocarcinoma. The patient did not have a prior history of lichen planus. Physical examination demonstrated well demarcated, violaceous papules and plaques in a circumferential band-like distribution on the bilateral gluteal, lumbosacral, and pelvic region. In addition, he had a few discrete lesions on the calves and dorsal feet. Punch biopsy revealed an acanthotic epidermis with "saw-tooth" rete ridges and a lichenoid inflammatory infiltrate. A diagnosis of hypertrophic lichen planus was made, reinforcing the importance for clinicians to recognize radiation therapy as a risk factor for developing lichen planus despite no prior history of lichen planus.

Enteric-coated and highly standardized cranberry extract reduces antibiotic and nonsteroidal anti-inflammatory drug use for urinary tract infections during radiotherapy for prostate carcinoma.

IntroductionWorldwide, bacterial resistance to antibiotic therapy is a major concern for the medical community. Antibiotic resistance mainly affects Gram-negative bacteria that are an important cause of lower urinary tract infections (LUTIs). Pelvic irradiation for prostate cancer is a risk factor for LUTIs. Cranberry extract is reported to reduce the incidence of LUTIs. The prophylactic role of an enteric-coated, highly standardized cranberry extract (VO370®) in reducing LUTI episodes, urinary discomfort, and nonsteroidal anti-inflammatory drug (NSAID) and antibiotic use during radiotherapy for prostate carcinoma was evaluated.MethodsA total of 924 patients with prostate carcinoma treated by radiotherapy to the prostatic and pelvic areas were randomized to receive (n=489) or not (n=435) the enteric-coated, highly standardized cranberry extract for 6–7 weeks concurrently with irradiation. Outcomes were analyzed by using Mann–Whitney U test and Pearson’s χ2 test. Primary endpoint was the number of patients with LUTI; secondary endpoints were incidence of recurrence, days of treatment with antibiotics and number of subjects treated with NSAIDs, and incidence of dysuria.ResultsThe treatment was very well tolerated, and there were no serious side effects. All enrolled patients completed the study. Urinary infections were detected in 53 of the 489 patients (10.8%) treated with enteric-coated, highly standardized cranberry extract, while 107 of the 435 patients (24.6%) in the control group developed LUTIs (p=0.0001). A clear and significant reduction in urinary discomfort of ~50% was seen in treated subjects. The treatment also resulted in ~50% reduction in the use of anti-inflammatory drugs and antibiotics.ConclusionThe enteric-coated, highly standardized cranberry extract could be used as a prophylactic to reduce the incidence of LUTIs and decrease antibiotic therapy in patients receiving pelvic irradiation for prostate cancer.

Integral Dose-Based Inverse Optimization May Reduce Side Effects in Radiotherapy of Prostate Carcinoma.

The purpose of this work is to apply a novel inverse optimization approach, based on utilization of quantitative imaging information in the optimization function, to prostate carcinoma. This new inverse optimization algorithm relies upon quantitative information derived from computed tomography (CT) imaging studies. The Hounsfield numbers of the CT voxels are converted to physical density, which in turn is used to calculate voxel mass and the corresponding integral dose, by summation over the product of dose and mass in each dose voxel. This integral dose is used for plan optimization through its global minimization. The optimization results are compared to the optimization results derived from most commonly used dose-volume-based inverse optimization, where objective functions are formed as summation over all dose voxels of the squared differences between voxel doses and user specified doses. The data from 25 prostate plans were optimized with dose-volume histogram (DVH) and integral dose (energy) minimization objective functions. The results obtained with the energy- and DVH-based optimization schemes were studied through commonly used dosimetric indices (DIs). Statistical equivalence tests were further performed to establish population-based significance results. Both DVH- and energy-based plans for each case were normalized so that 95% of the planning target volume receives the prescription dose. The average differences for the rectum and bladder DIs ranged from 1.6 to 25%, where the energy-based quantities were lower. For both femoral heads, the energy-based optimization-derived doses were lower on average by 32%. The statistical tests demonstrated that the significant differences in the tallied dose indices range from 2.7% to more than 50% for rectum, bladder, and femoral heads. For majority of the clinically relevant dosimetric quantities, energy-based inverse optimization performs better than the standard of care DVH-based optimization in prostate carcinoma. The population averaged statistically significant differences range from ~3 to ~50%. Therefore, this newly proposed optimization approach, incorporating explicitly quantitative imaging information in the inverse optimization function, holds potential for further reduction of complication rates in prostate cancer.

Malva sylvestaris preventive effect on urinary toxicity of radiotherapy for prostate carcinoma

Malva sylvestaris preventive effect on urinary toxicity of radiotherapy for prostate carcinoma

Predictors of radiation-induced gastrointestinal morbidity: A prospective, longitudinal study following radiotherapy for carcinoma of the prostate

Background Chronic gastrointestinal (GI) morbidity occurs in ≥50% of patients after external beam radiotherapy (EBRT) for carcinoma of prostate (CaP). This prospective, longitudinal study examines which baseline measurements of: 1) homocysteine and micronutrients in plasma; 2) chromosome damage/misrepair biomarkers; and 3) anal and rectal dose volume metrics predict GI morbidity after EBRT.Patients and methods In total, 106 patients with CaP had evaluations of GI symptoms (modified LENT-SOMA questionnaires) before EBRT and at one month, one, two and three years after its completion. Other variables measured before EBRT were: 1) plasma concentrations of homocysteine and micronutrients including caroteinoids and selenium; 2) chromosome damage/DNA misrepair (micronuclei/nucleoplasmic bridge) indices; and 3) mean anal and rectal wall doses and volumes of anal and rectal walls receiving ≥40 Gy and ≥60 Gy. Univariate and multivariate analyzes examined the relationships among: 1) plasma levels of homocysteine and micronutrients; 2) indices of chromosome damage/DNA misrepair; and 3) mean anal and rectal wall doses and volumes of anal and rectal walls receiving ≥40 Gy and ≥60 Gy and total GI symptom scores from one month to three years after EBRT.Results Increased frequency and urgency of defecation, rectal mucous discharge and bleeding after EBRT resulted in sustained rises in total GI symptom scores above baseline at three years. On univariate analysis, total GI symptom scores were significantly associated with: 1) plasma selenium and α tocopherol; 2) micronuclei indices of DNA damage; 3) mean anal and rectal wall doses; and 4) volumes of anal and rectal wall receiving ≥40 Gy and ≥60 Gy (p = 0.08–<0.001). On multivariate analysis, only volume of anal wall receiving ≥40 Gy was significant for increased GI symptoms after EBRT (p < 0.001).Conclusion The volume of anal wall receiving ≥40 Gy predicts chronic GI morbidity after EBRT for CaP.

PROSTATIC CARCINOMA

Introduction: During the past many years the availability of serum PSAas a screening marker, has encouraged its use to diagnose both prostatic cancer and itsrecurrence. Patients with high S/PSA are at increased risk of advanced carcinoma prostate andscreening at an earlier stage would help to manage it accordingly. The aim of this study wasto determine association between serum prostatic specific antigen (PSA) levels and Gleasongrade in prostatic carcinoma patients. Study Design: Descriptive, case series study. Setting:Department of Urology &amp; Renal Transplantation in collaboration with Institutional laboratoryof Bahawal Victoria Hospital, Bahawalpur. Period: June 2012 to June 2014. Materials &amp;Methods: Total 160 patients of age 50-80 years with biopsy proven prostatic carcinoma wereincluded. Patients with h/o radiotherapy for prostatic carcinoma and anti-androgen therapywere excluded. Histological slides of each patient were reviewed by using the Gleason gradingsystem. Gleason grade of each patient was correlated with his serum prostatic specific antigen(PSA) report which was done before surgery or biopsy. Results: In our study, mean age was66.89 ± 9.28 years. Mean serum PSA was 21.41 ± 13.67 ng/ml. Intermediate grade cancerwas found in 38.75% patients followed by moderate to poorly differentiated cancer in 31.86%patients. Gleason score ≥7 was significantly higher in patients with serum PSA &gt;20 ng/mL thanthose with serum PSA ≤ 20 ng/mL (p-value of 0.000). So, serum PSA was positively correlatedwith gleason grade (OR = 3.67, Cl = 95%, P = 0.0001) Conclusion: This study concludedthat there is statistically significant association between serum prostatic specific antigen (PSA)levels and Gleason grade in prostatic carcinoma patients and patients with high prostatespecific antigen are at increased risk of advanced carcinoma prostate.

Gastrointestinal Dose-Histogram Effects in the Context of Dose-Volume–Constrained Prostate Radiation Therapy: Analysis of Data From the RADAR Prostate Radiation Therapy Trial

To use a high-quality multicenter trial dataset to determine dose-volume effects for gastrointestinal (GI) toxicity following radiation therapy for prostate carcinoma. Influential dose-volume histogram regions were to be determined as functions of dose, anatomical location, toxicity, and clinical endpoint. Planning datasets for 754 participants in the TROG 03.04 RADAR trial were available, with Late Effects of Normal Tissues (LENT) Subjective, Objective, Management, and Analytic (SOMA) toxicity assessment to a median of 72 months. A rank sum method was used to define dose-volume cut-points as near-continuous functions of dose to 3 GI anatomical regions, together with a comprehensive assessment of significance. Univariate and multivariate ordinal regression was used to assess the importance of cut-points at each dose. Dose ranges providing significant cut-points tended to be consistent with those showing significant univariate regression odds-ratios (representing the probability of a unitary increase in toxicity grade per percent relative volume). Ranges of significant cut-points for rectal bleeding validated previously published results. Separation of the lower GI anatomy into complete anorectum, rectum, and anal canal showed the impact of mid-low doses to the anal canal on urgency and tenesmus, completeness of evacuation and stool frequency, and mid-high doses to the anorectum on bleeding and stool frequency. Derived multivariate models emphasized the importance of the high-dose region of the anorectum and rectum for rectal bleeding and mid- to low-dose regions for diarrhea and urgency and tenesmus, and low-to-mid doses to the anal canal for stool frequency, diarrhea, evacuation, and bleeding. Results confirm anatomical dependence of specific GI toxicities. They provide an atlas summarizing dose-histogram effects and derived constraints as functions of anatomical region, dose, toxicity, and endpoint for informing future radiation therapy planning.

Management of Recurrent Rectourethral Fistula by York Mason Posterior Transrectal Transsphincteric Approach.

Rectourethral fistula (RUF) may develop after ureterovesical and rectal intervention or radiation therapy (RT) rarely, but it is associated with significant morbidity and mortality. The patient will typically present with pneumaturia, faecaluria, and urinary drainage from the rectum. Diagnosis can be easily done with digital rectal examination, cystography, and urethrocystoscopy. Conservative supportive management of RUF does not appear to be successful in most patients, and management with surgical intervention remains the best treatment option. Several surgical techniques have been described including transabdominal, transanal, transperineal, combined abdominoperineal, anterior and posterior transsphincteric, transsacral, laparoscopic, robotic, and endoscopic minimally invasive approaches. There have been very few data about treatment of recurrent RUF. We would like to report the management of recurrent RUF following transurethral resection of prostate and RT for prostate carcinoma in an immunosuppressed, 75-year-old patient by York Mason posterior transrectal transsphincteric approach.

Mo2018 Evidence of Abnormal Pudendal Nerve Function in Men With Fecal Incontinence After Radiotherapy for Prostate Cancer

Carcinoma of the prostate is a significant cause of mortality and morbidity worldwide and is the most common non-cutaneous malignancy in American men. External beam radiotherapy (EBRT) for locally advanced prostate carcinoma is associated with a halving of the 10-year prostate cancer mortality. A frequent complication of EBRT is fecal incontinence, which significantly impairs quality of life for patients. Pelvic nerve damage as a result of the radiotherapy has been implicated as a possible cause of fecal incontinence. The aim of this study was to determine if fecal incontinence severity and pudendal nerve dysfunction were more commonly associated with men that had undergone EBRT for prostate cancer than in men with fecal incontinence with no history of prostate cancer or pelvic floor radiotherapy. Methods: At Flinders Medical Centre 1305 patients underwent anorectal physiology testing between January 1998 andNovember 2013. 114men were investigated for fecal incontinence with pudendal nerve terminal motor latency (PNTML) testing and anal manometry. Men with evidence of sphincter injury on endoanal ultrasound (EUS) (n=34), a missing EUS result (n=2) or who had received radiotherapy for causes other than prostate cancer (n=4) were excluded. Of the remaining 74 men, 17 had previously undergone radiotherapy for prostate carcinoma (presenting for anorectal testing on average 8.8 years post EBRT) and 57 had no reported prostate cancer. Pudendal nerve function, mean resting pressures (MRP), squeeze pressures (MSP) and Wexner incontinence scores, were compared between the two groups. Results The non-radiotherapy group (62±17 yrs; range 18-85) and a mean Wexner incontinence score of 8 ± 4 which was significantly less (p<0.005) than the mean score of 13 ± 3 in the radiotherapy group (77 ± 6 yrs; range 67-86). In the non-radiotherapy group, 21.7% had abnormal bilateral PNTML compared to 87.5% in the radiotherapy group (p<0.001, Chi-Square). 15.2% in the non-radiotherapy group had delayed bilateral or unilateral PNTML compared to 25.1% in the radiotherapy group (p<0.001). 6.5% of patients in the non-radiotherapy group had no unilateral or bilateral pudendal nerve response (no sphincter contraction in response to stimulus) compared to 62.6% in the radiotherapy group (p<0.001). MRP was 83 ± 40 cmH20 (normal range 54-124 cmH20) in the nonradiotherapy group compared to 55 ± 29 cm H20 in the radiotherapy group (p<0.05). MSP was 246 ± 74 cm H20 (normal range 179-317 cmH20) in the non-radiotherapy group compared to 190 ± 90 cm H20 in the radiotherapy group (p<0.05). Conclusions. Abnormal pudendal nerve function is associated with incontinent males who have received radiotherapy for prostate cancer. This study suggests that pelvic nerve damage as a result of radiotherapy may play a role in the fecal functional disorders experienced by many post-EBRT men.

Mo2019 Three-Dimensional High-Resolution Manometry in the Assessment of Anal Sphincter Defects in Patients With Incontinence: Correlation With Symptom Scores and Endoanal Ultrasonography

Carcinoma of the prostate is a significant cause of mortality and morbidity worldwide and is the most common non-cutaneous malignancy in American men. External beam radiotherapy (EBRT) for locally advanced prostate carcinoma is associated with a halving of the 10-year prostate cancer mortality. A frequent complication of EBRT is fecal incontinence, which significantly impairs quality of life for patients. Pelvic nerve damage as a result of the radiotherapy has been implicated as a possible cause of fecal incontinence. The aim of this study was to determine if fecal incontinence severity and pudendal nerve dysfunction were more commonly associated with men that had undergone EBRT for prostate cancer than in men with fecal incontinence with no history of prostate cancer or pelvic floor radiotherapy. Methods: At Flinders Medical Centre 1305 patients underwent anorectal physiology testing between January 1998 andNovember 2013. 114men were investigated for fecal incontinence with pudendal nerve terminal motor latency (PNTML) testing and anal manometry. Men with evidence of sphincter injury on endoanal ultrasound (EUS) (n=34), a missing EUS result (n=2) or who had received radiotherapy for causes other than prostate cancer (n=4) were excluded. Of the remaining 74 men, 17 had previously undergone radiotherapy for prostate carcinoma (presenting for anorectal testing on average 8.8 years post EBRT) and 57 had no reported prostate cancer. Pudendal nerve function, mean resting pressures (MRP), squeeze pressures (MSP) and Wexner incontinence scores, were compared between the two groups. Results The non-radiotherapy group (62±17 yrs; range 18-85) and a mean Wexner incontinence score of 8 ± 4 which was significantly less (p<0.005) than the mean score of 13 ± 3 in the radiotherapy group (77 ± 6 yrs; range 67-86). In the non-radiotherapy group, 21.7% had abnormal bilateral PNTML compared to 87.5% in the radiotherapy group (p<0.001, Chi-Square). 15.2% in the non-radiotherapy group had delayed bilateral or unilateral PNTML compared to 25.1% in the radiotherapy group (p<0.001). 6.5% of patients in the non-radiotherapy group had no unilateral or bilateral pudendal nerve response (no sphincter contraction in response to stimulus) compared to 62.6% in the radiotherapy group (p<0.001). MRP was 83 ± 40 cmH20 (normal range 54-124 cmH20) in the nonradiotherapy group compared to 55 ± 29 cm H20 in the radiotherapy group (p<0.05). MSP was 246 ± 74 cm H20 (normal range 179-317 cmH20) in the non-radiotherapy group compared to 190 ± 90 cm H20 in the radiotherapy group (p<0.05). Conclusions. Abnormal pudendal nerve function is associated with incontinent males who have received radiotherapy for prostate cancer. This study suggests that pelvic nerve damage as a result of radiotherapy may play a role in the fecal functional disorders experienced by many post-EBRT men.

Angiosarcoma of the prostate: a more frequent finding in the future owing to radiotherapy? A literature review with treatment implications based on a case report

Objective. An increase in the incidence of prostate angiosarcoma may be expected owing to the exponential increase in the use of radiotherapy for prostate carcinoma in recent decades and the possible aetiology of radiation exposure on the development of angiosarcoma in general. The objective of this study was to give an overview of cases in the literature based on a case report of prostate angiosarcoma in a hospital in the Netherlands, and to discuss optimal treatment. Material and methods. All (related) articles In PubMed/Medline and Embase with possible cases of angiosarcoma were screened on title and abstract. A case of prostate angiosarcoma identified in the authors' institution was included. Results. The literature search yielded 13 cases of prostate angiosarcoma. The earliest six publications lack essential data. Four patients had a history of radiotherapy. The present patient developed angiosarcoma following brachytherapy for prostate cancer. Therapy consisted of radical surgery with or without chemotherapy in five cases. In eight cases curative therapy was not reported or not possible. Mean follow-up was only 1 year. Four patients died within 1 year of diagnosis, irrespective of treatment choice. One patient, treated with a combination of radical surgery and adjuvant chemotherapy, was still alive 36 months after therapy. Conclusions. The findings confirm that prostate angiosarcoma is mostly radiation induced. This patient is the first case of prostate angiosarcoma after primary brachytherapy. Angiosarcoma may occur more often in the future owing to widespread use of brachytherapy and radiotherapy of the prostate. Current guidelines on management of angiosarcoma suggest radical surgery in local disease as the primary treatment of choice.

Argon Plasma Coagulation Therapy Versus Topical Formalin for Intractable Rectal Bleeding and Anorectal Dysfunction After Radiation Therapy for Prostate Carcinoma

To evaluate and compare the effect of argon plasma coagulation (APC) and topical formalin for intractable rectal bleeding and anorectal dysfunction associated with chronic radiation proctitis. Thirty men (median age, 72 years; range, 49-87 years) with intractable rectal bleeding (defined as ≥1× per week and/or requiring blood transfusions) after radiation therapy for prostate carcinoma were randomized to treatment with APC (n=17) or topical formalin (n=13). Each patient underwent evaluations of (1) anorectal symptoms (validated questionnaires, including modified Late Effects in Normal Tissues-Subjective, Objective, Management, and Analytic and visual analogue scales for rectal bleeding); (2) anorectal motor and sensory function (manometry and graded rectal balloon distension); and (3) anal sphincteric morphology (endoanal ultrasound) before and after the treatment endpoint (defined as reduction in rectal bleeding to 1× per month or better, reduction in visual analogue scales to ≤25 mm, and no longer needing blood transfusions). The treatment endpoint was achieved in 94% of the APC group and 100% of the topical formalin group after a median (range) of 2 (1-5) sessions of either treatment. After a follow-up duration of 111 (29-170) months, only 1 patient in each group needed further treatment. Reductions in rectal compliance and volumes of sensory perception occurred after APC, but no effect on anorectal symptoms other than rectal bleeding was observed. There were no differences between APC and topical formalin for anorectal symptoms and function, nor for anal sphincteric morphology. Argon plasma coagulation and topical formalin had comparable efficacy in the durable control of rectal bleeding associated with chronic radiation proctitis but had no beneficial effect on anorectal dysfunction.

Utilization of cone‐beam CT for reconstruction of dose distribution delivered in image‐guided radiotherapy of prostate carcinoma — bony landmark setup compared to fiducial markers setup

The purpose of this study was to compare two different styles of prostate IGRT: bony landmark (BL) setup vs. fiducial markers (FM) setup. Twenty‐nine prostate patients were treated with daily BL setup and 30 patients with daily FM setup. Delivered dose distribution was reconstructed on cone‐beam CT (CBCT) acquired once a week immediately after the alignment. Target dose coverage was evaluated by the proportion of the CTV encompassed by the 95% isodose. Original plans employed 1 cm safety margin. Alternative plans assuming smaller 7 mm margin between CTV and PTV were evaluated in the same way. Rectal and bladder volumes were compared with initial ones. While the margin reduction in case of BL setup makes the prostate coverage significantly worse (p=0.0003, McNemar's test), in case of FM setup with the reduced 7 mm margin, the prostate coverage is even better compared to BL setup with 10 mm margin (p=0.049, Fisher's exact test). Moreover, partial volumes of organs at risk irradiated with a specific dose can be significantly lowered (p<0.0001, unpaired t‐test). Reducing of safety margin is not acceptable in case of BL setup, while the margin can be lowered from 10 mm to 7 mm in case of FM setup.PACS numbers: 87.55.dk, 87.55.km, 87.55.tm

A Dosimetric Comparison in Prostate Cancer Patients Treated with HDR Brachytherapy ± IMRT ± Polyethylene Glycol Gel

Because of the proximity of the anterior rectal wall to the prostate, rectal toxicity is a potential complication of radiation therapy for prostatic carcinoma. We evaluated the dosimetric impact due to use of a bioabsorbable polyethylene glycol gel to increase the separation between the prostate and rectum in prostate cancer patients undergoing high-dose-rate (HDR) brachytherapy ± intensity modulated radiation therapy (IMRT).

Transperineal Implementation of Biocompatible Balloon in Patients Treated With Radiotherapy for Prostate Carcinoma: Feasibility and Quality Assurance Study in Terms of Anatomical Stabilization Using Image Registration Techniques

The purpose of this study was to evaluate the feasibility of the transperineal implementation of biocompatible balloon (Prospace®) as well as the quality assurance of the procedure in terms of anatomical stabilization of the implant and reproductivity of treatment parameters during radiation therapy. Between December 2011 and February 2012, ten patients diagnosed with localized low risk prostate cancer, GS <7, PSA <10, cT1-2, were treated with external three dimensional conformal radiation therapy (3DCRT). Before the initiation of treatment, the Prospace® balloon was implanted by a minimally invasive procedure, though the perineum in the intermediate space between the rectum and the prostate. All patients underwent 3DCRT with 76-78 Gy in 38-39 daily fractions (2.0 Gy/ fraction). We evaluated the implant stabilization by examining by Computed Tomography its position right after implantation and three weeks after initiation of treatment, by using non-rigid registration technique. We also evaluated the acute toxicity according to EORTC/RTOG radiation toxicity criteria and also according to Subjective-RectoSigmoid (S-RS) scale based on the endoscopic terminology of the World Organization for Digestive Endoscopy, as well as pain related to Prospace implementation according to Visual Analogue Score (VAS). By using registration techniques, the Prospace device was found stable in sequential CTs with x,y,z-axis displacements up to 2.1 mm, 3 mm and 2.2 mm, respectively. The mean VAS score related to Prospace was 1.4(± 0.5) and the mean score of rectal toxicity according to S-RS score was 1.9(± 0.6). The implementation of PROSPACE is feasible. Implant’s position is relative stable. The procedure is minimally invasive with no recorded side effects. The incidence of patient-reported acute Gastrointestinal (GI) and Genitourinary (GU) toxicity as well as findings from flexible rectosigmoidoscopy, following high dose of 3DCRT after the prospace implantation, were low. The study is on-going and further results with analyzed data from more patients will be reported.

Role of Early Proctoscopy in Predicting Late Symptomatic Proctitis After External Radiation Therapy for Prostate Carcinoma

To determine whether acute radiation-proctitis, diagnosed by proctoscopy after radiation therapy for prostate cancer, can predict late clinical proctitis. 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. 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). 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.

Enteric-coated, highly standardized cranberry extract reduces risk of UTIs and urinary symptoms during radiotherapy for prostate carcinoma

BackgroundCranberry (Vaccinium macrocarpon) proanthocyanidins can interfere with adhesion of bacteria to uroepithelial cells, potentially preventing lower urinary tract infections (LUTIs). Because LUTIs are a common side effect of external beam radiotherapy (EBRT) for prostate cancer, we evaluated the clinical efficacy of enteric-coated tablets containing highly standardized V. msacrocarpon (ecVM) in this condition.MethodsA total of 370 consecutive patients were entered into this study. All patients received intensity-modulated radiotherapy for prostate cancer; 184 patients were also treated with ecVM while 186 served as controls. Cranberry extract therapy started on the simulation day, at which time a bladder catheterization was performed. During EBRT (over 6–7 weeks), all patients underwent weekly examination for urinary tract symptoms, including regular urine cultures during the treatment period.ResultsCompliance was excellent, with no adverse effects or allergic reactions being observed, apart from gastric pain in two patients. In the cranberry cohort (n = 184), 16 LUTIs (8.7%) were observed, while in the control group (n = 186) 45 LUTIs (24.2%) were recorded. This difference was statistically significant. Furthermore, lower rates of nocturia, urgency, micturition frequency, and dysuria were observed in the group that received cranberry extract.ConclusionCranberry extracts have been reported to reduce the incidence of LUTIs significantly in women and children. Our data extend these results to patients with prostate cancer undergoing irradiation to the pelvis, who had a significant reduction in LUTIs compared with controls. These results were accompanied by a statistically significant reduction in urinary tract symptoms (dysuria, nocturia, urinary frequency, urgency), suggesting a generally protective effect of cranberry extract on the bladder mucosa.

Pathophysiology and Natural History of Anorectal Sequelae Following Radiation Therapy for Carcinoma of the Prostate

To characterize the prevalence, pathophysiology, and natural history of chronic radiation proctitis 5 years following radiation therapy (RT) for localized carcinoma of the prostate. Studies were performed in 34 patients (median age 68 years; range 54-79) previously randomly assigned to either 64 Gy in 32 fractions over 6.4 weeks or 55 Gy in 20 fractions over 4 weeks RT schedule using 2- and later 3-dimensional treatment technique for localized prostate carcinoma. Each patient underwent evaluations of (1) gastrointestinal (GI) symptoms (Modified Late Effects in Normal Tissues Subjective, Objective, Management and Analytic scales including effect on activities of daily living [ADLs]); (2) anorectal motor and sensory function (manometry and graded balloon distension); and (3) anal sphincteric morphology (endoanal ultrasound) before RT, at 1 month, and annually for 5 years after its completion. Total GI symptom scores increased after RT and remained above baseline levels at 5 years and were associated with reductions in (1) basal anal pressures, (2) responses to squeeze and increased intra-abdominal pressure, (3) rectal compliance and (4) rectal volumes of sensory perception. Anal sphincter morphology was unchanged. At 5 years, 44% and 21% of patients reported urgency of defecation and rectal bleeding, respectively, and 48% impairment of ADLs. GI symptom scores and parameters of anorectal function and anal sphincter morphology did not differ between the 2 RT schedules or treatment techniques. Five years after RT for prostate carcinoma, anorectal symptoms continue to have a significant impact on ADLs of almost 50% of patients. These symptoms are associated with anorectal dysfunction independent of the RT schedules or treatment techniques reported here.

Localized Porokeratosis Secondary to Ionizing Radiotherapy for Prostate Carcinoma

Localized Porokeratosis Secondary to Ionizing Radiotherapy for Prostate Carcinoma

Interfractional Variations in the Setup of Pelvic Bony Anatomy and Soft Tissue, and Their Implications on the Delivery of Proton Therapy for Localized Prostate Cancer

To quantify daily variations in the anatomy of patients undergoing radiation therapy for prostate carcinoma, to estimate their effect on dose distribution, and to evaluate the effectiveness of current standard planning and setup approaches employed in proton therapy. We used series of computed tomography data, which included the pretreatment scan, and between 21 and 43 in-room scans acquired on different treatment days, from 10 patients treated with intensity-modulated radiation therapy at Morristown Memorial Hospital. Variations in femur rotation angles, thickness of subcutaneous adipose tissue, and physical depth to the distal surface of the prostate for lateral beam arrangement were recorded. Proton dose distributions were planned with the standard approach. Daily variations in the location of the prescription isodose were evaluated. In all 10 datasets, substantial variation was observed in the lateral tissue thickness (standard deviation of 1.7-3.6 mm for individual patients, variations of >5 mm from the planning computed tomography observed in all series), and femur rotation angle (standard deviation between 1.3° and 4.8°, with the maximum excursion exceeding 10° in 6 of 10 datasets). Shifts in the position of treated volume (98% isodose) were correlated with the variations in the lateral tissue thickness. Analysis suggests that, combined with image-guided setup verification, the range compensator expansion technique prevents loss of dose to target from femur rotation and soft-tissue deformation, in the majority of cases. Anatomic changes coupled with the uncertainties of particle penetration in tissue restrict possibilities for margin reduction in proton therapy of prostate cancer.