Gleason score 7 prostate cancer treated with interstitial brachytherapy with or without supplemental external beam radiation and androgen deprivation therapy: Is the primary pattern on needle biopsy prognostic?

PurposeTo evaluate the effect of primary Gleason pattern on biochemical progression-free survival (bPFS), cause-specific survival (CSS), and overall survival (OS) in Gleason 7 prostate cancer patients treated with low-dose-rate (LDR) interstitial brachytherapy with or without supplemental external beam radiation therapy and androgen deprivation therapy.Methods and MaterialsWe retrospectively reviewed the medical records of 932 consecutive patients with biopsy-confirmed Gleason 7 prostate cancer who received LDR interstitial brachytherapy as a component of their definitive treatment regimen. Treatment outcomes were compared between patients with primary Gleason pattern 3 and 4.ResultsWith a median followup of 7.4 years, the 10- and 14-year bPFS, CSS, and OS for the entire Gleason 7 study group were 95.7/95.7%, 98.6/98.6% and 77.2/64.3%, respectively. When biochemical control was evaluated as a function of primary Gleason pattern, the primary pattern 3 had a statistically higher 10- and 14-year bPFS (97.8/97.8% vs. 93.1/93.1%, p = 0.006). The Gleason pattern 3 patients also trended toward a higher 10- and 14-year CSS (99.3/99.3% vs. 96.9/96.9%, p = 0.058). OS was not statistically different between the two Gleason 7 cohorts.ConclusionsGleason 7 prostate cancer patients treated with LDR interstitial brachytherapy have an excellent long-term outcome. There was a small but statistically significant advantage in bPFS and a trend toward improved CSS in patients with a primary Gleason pattern of 3.     

Factors impacting all-cause mortality in prostate cancer brachytherapy patients with or without androgen deprivation therapy

PurposeCertain subsets of patients have an increased risk of all-cause mortality when androgen deprivation therapy (ADT) is used with definitive radiotherapy. We evaluated the relationship between pretreatment serum testosterone, age, and comorbidities on survival after prostate brachytherapy in men treated with and without ADT.Methods and MaterialsFrom October 2001 to September 2005, 803 patients underwent brachytherapy and 720 had a pretreatment serum testosterone. Comorbidities were prospectively recorded for each patient (body mass index > 30, hypertension, diabetes, current smoker). Median followup was 5.0 years. 34.2% of the patients received ADT. Focus was on subset of men who might be expected to have more significant side effects associated with ADT.ResultsADT did not significantly impact overall survival (OS) in men <65 years, >65 years, with one or no comorbidities, with more than one comorbidity, or with normal/high testosterone level. ADT use in men with low testosterone level was associated with decreased OS (83.6% vs. 93.1%, p = 0.01). The adverse impact of ADT in men with low testosterone level was restricted to men with low testosterone level and more than one comorbidity (OS of 71.3% vs. 92.8%, p < 0.01), with death from cardiovascular diseases accounting for almost all of the excess mortality. The subset of men with multiple comorbidities and normal/high testosterone level did not experience adverse OS with ADT.ConclusionsLow pretreatment testosterone level may be a marker for men at increased risk of premature death with ADT. The combination of low pretreatment serum testosterone level and multiple preexisting comorbidities is associated with decreased OS when ADT is incorporated into treatment.     

Identification of comorbidities that place men at highest risk of death from androgen deprivation therapy before brachytherapy for prostate cancer

PurposeTo determine which specific comorbidities predispose men to excess mortality by androgen deprivation therapy (ADT) given before and during brachytherapy for prostate cancer.Methods and MaterialsWe analyzed 5972 men with T1c–T3b prostate cancer treated with brachytherapy-based radiation with or without neoadjuvant ADT. Cox multivariable analysis with propensity scoring was used to determine if ADT was associated with increased all-cause mortality (ACM) in men divided into groups stratified by cardiac comorbidities. Tests for interaction between risk group and outcome were performed.ResultsADT was associated with increased ACM in men with a history of myocardial infarction or congestive heart failure, regardless of whether they underwent revascularization (adjusted hazard ratio [AHR], 2.1 [95% confidence interval {CI}, 1.02–4.17; p = 0.04]) or not (AHR, 1.8 [95% CI, 1.05–3.20; p = 0.03]), but this effect was not seen in men with less severe comorbidity. However, among men with diabetes, there was a significant interaction with risk group (p = 0.01) such that ADT was associated with excess mortality in men with low-risk disease (AHR = 2.21 [1.04–4.68]; p = 0.04) but not in men with intermediate or high-risk disease (AHR, 0.64 [0.33–1.22]; p = 0.17).ConclusionsADT was associated with excess ACM in all patients with a history of congestive heart failure or myocardial infarction, regardless of whether they were revascularized, and in diabetics with low-risk disease. ADT for gland downsizing before brachytherapy should be avoided in these men.     

Clinical outcomes of high-dose-rate brachytherapy and external beam radiotherapy in the management of clinically localized prostate cancer

PurposeTo report prostate-specific antigen (PSA) relapse-free survival and treatment-related toxicity outcomes after combining high-dose-rate (HDR) brachytherapy with external beam radiotherapy (EBRT) for patients with clinically localized prostate cancer.Methods and MaterialsBetween 1998 and 2009, 229 patients were treated with HDR brachytherapy followed 3 weeks later by supplemental EBRT. The HDR brachytherapy boost consisted of three fractions of ¹⁹²Ir (5.5–7.5 Gy per fraction), and EBRT consisted of intensity-modulated radiotherapy delivering an additional 45.0–50.4 Gy directed to the prostate gland and seminal vesicles. Median follow-up was 61 months.ResultsSeven-year PSA relapse-free survival for low-, intermediate-, and high-risk patients were 95%, 90%, and 57%, respectively (p < 0.001). Among high-risk patients treated with biological equivalent doses in excess of 190 Gy, 7-year PSA relapse-free survival was 81%. In multivariate analysis, Gleason scores of ≥8 predicted for increased risk of biochemical failure, whereas the use of short-term neoadjuvant androgen deprivation therapy did not influence tumor-control outcomes even among intermediate- or high-risk patients. Seven-year incidence of distant metastases for low-, intermediate-, and high-risk patients were 5%, 3%, and 17%, respectively. Seven-year incidence of late Grade 2 and 3 genitourinary toxicities were 22.1% and 4.9%, respectively and the 7-year incidence of Grade 2 and 3 gastrointestinal toxicities were 1% and 0.4%, respectively.ConclusionHDR prostate brachytherapy in conjunction with supplemental EBRT results in excellent biochemical relapse-free survival rates with a low incidence of severe late genitourinary or gastrointestinal toxicities. The use of short-term neoadjuvant androgen deprivation did not influence long-term biochemical tumor control in this cohort.     

Variations in patterns of concurrent androgen deprivation therapy use based on dose escalation with external beam radiotherapy vs. brachytherapy boost for prostate cancer

PurposeRetrospective data suggest less benefit from androgen deprivation therapy (ADT) in the setting of dose-escalated definitive radiation for prostate cancer, especially when a combination of external beam radiotherapy (EBRT) and brachytherapy approaches are used. This study aimed to test the hypothesis that patients with prostate cancer with intermediate- or high-risk disease undergoing extreme dose escalation with a brachytherapy boost are less likely to receive ADT.Methods and MaterialsData from the National Cancer Database were extracted for men aged 40–90 years diagnosed with node-negative, non-metastatic prostate cancer from 2004 to 2015. Only patients with intermediate- or high-risk disease who were treated with definitive radiotherapy were included. The association and patterns of care between dose escalated radiotherapy and ADT receipt were assessed using multivariable logistic regression.ResultsPatients with unfavorable intermediate- and high-risk prostate cancer were significantly less likely to receive ADT if they underwent dose escalation with a combination of EBRT and brachytherapy (odds ratio 0.67, p < 0.0001). Over time, this decrease in ADT utilization has widened for patients with unfavorable intermediate-risk disease. There was no difference in ADT utilization when comparing patients treated with non–dose-escalated EBRT to those treated with dose-escalated EBRT (without brachytherapy).ConclusionIn this large national database, patients with unfavorable intermediate- and high-risk prostate cancer were significantly less likely to receive guideline-indicated ADT if they underwent extreme dose escalation with combined radiation modalities. As we await prospective data guiding the utility of ADT with dose escalated radiation, these findings suggest potential underutilization of ADT in patients at higher risk of advanced disease.     

Knife or needles? A cohort analysis of outcomes after radical prostatectomy or brachytherapy for men with low- or intermediate-risk adenocarcinoma of the prostate

PurposeThe purpose of this study was to evaluate long-term outcomes for men with early stage prostate cancer treated with radical prostatectomy (RP) or brachytherapy (BT) at a single tertiary care center.Methods and MaterialsWe retrospectively analyzed data from 371 men with clinical T1a–T2c disease with prostate-specific antigen level <20 ng/mL and Gleason score (GS) 6–7 who were treated with RP (n = 279) or BT (n = 92) at MD Anderson Cancer Center in 2000–2001. Biochemical recurrence–free survival (BRFS) and prostate cancer–specific survival rates were compared by treatment modality.ResultsThe median followup time was 7.2 and 7.6 years for patients treated with RP and BT, respectively. Disease was upgraded from GS 6 to 7 after central review of the biopsy specimen for 36 men treated with RP (12.9%) and 15 men treated with BT (16.3%). After RP, GS was upgraded in 121 men (43.4%) between the centrally reviewed biopsy and the RP specimen. After RP, 5-year BRFS rates were 96.1% and 90.6% for low- and intermediate-risk disease, respectively (p = 0.003). After BT, 5-year BRFS rates were 92.5% and 95.8% for low- and intermediate-risk disease, respectively (p = 0.017). After RP or BT, 5-year BRFS rates were not significantly different with GS upgraded. Five-year prostate cancer–specific survival rates for patients with upgraded GS were 100% for both RP and BT.ConclusionsExcellent disease control outcomes can be achieved after either RP or BT as monotherapy for men with early stage prostate cancer. Upgrading of GS from 6 to 7, either (3 + 4) or (4 + 3), did not predict for worse outcomes.     

Long-term outcomes with high-dose-rate brachytherapy for the management of base of tongue cancer

PurposeTo report the long-term results of a prospective, nonrandomized clinical trial using high-dose-rate (HDR) brachytherapy (BT) for the management of base of the tongue (BOT) tumors.Methods and MaterialsBetween January 1992 and June 2011, 60 patients (mean age, 57 years; range, 36–78 years) with T1–T4 and N0-3 carcinoma of BOT were treated. Fifty-six patients (93%) had advanced (Stage III-IV) disease. HDR BT boost (mean dose, 17 Gy; range, 12–30 Gy) was delivered after 50–70 Gy (mean 62 Gy) locoregional external beam irradiation. Seventeen patients (28%) received radiochemotherapy (RCT) with cisplatin.ResultsThe 5-year actuarial rate of local tumor control, locoregional tumor control, overall survival (OS), and cancer-specific survival (CSS) was 57%, 50%, 47%, and 61%, respectively. OS was significantly better in patients (n = 17) receiving RCT (69% vs. 39%; p = 0.005). Delayed soft-tissue ulceration occurred in seven patients (12%). Only one patient (<2%) developed osteoradionecrosis. In univariate analysis, the tumor size (T1–T2–T3 vs. T4) was found to have a significant effect on CSS (p = 0.043), whereas the nodal status (N0 vs. N+) affected locoregional tumor control (p = 0.042), OS (p = 0.002), and CSS (p = 0.015). Low histologic grade (1–2) was associated with better CSS (p = 0.020), whereas RCT significantly improved OS (p = 0.012).ConclusionsExternal beam irradiation combined with interstitial HDR BT boost results in good local tumor control with an acceptable rate of late side effects in patients with BOT carcinoma. RCT improves OS. Our results are similar to those reported with traditional low-dose-rate BT implants.     

Prostate cancer control and survival in Vietnam veterans exposed to Agent Orange

BackgroundIn this study, we evaluated the impact of Agent Orange exposure on survival in Vietnam Veterans undergoing prostate brachytherapy.Methods and MaterialFrom May 1995 to January 2005, 81 Vietnam veterans (29 with Agent Orange exposure and 52 without) and 433 nonveterans of comparable age (mean age, 58 years) underwent prostate brachytherapy. The mean follow-up was 5.0 years. Biochemical progression-free survival (bPFS) was defined as a prostate-specific antigen (PSA) ≤ 0.40 ng/mL after nadir. Patients with metastatic prostate cancer or hormone refractory disease without obvious metastases who died of any cause were classified as died of prostate cancer. All other deaths were attributed to the immediate cause of death. Multiple parameters were evaluated for impact on survival.ResultsAt 9 years, Agent Orange–exposed men were least likely to remain biochemically controlled (89.5%, 100%, and 97.2% in Agent Orange–exposed, nonexposed veterans, and nonveterans, respectively, p = 0.012). No significant differences in cause-specific (CSS) (p = 0.832) or overall survival (OS) (p = 0.363) were discerned. In multivariate analysis, CSS was best predicted by Gleason Score and day 0 D₉₀, whereas Gleason Score, % positive biopsies, and D₉₀ predicted for bPFS. None of the evaluated parameters predicted for OS, however, a trend was identified for better OS in younger patients and those with a higher D₉₀. In addition, Agent Orange exposure did not predict for any of the survival parameters. To date, 22 patients have died (metastatic prostate cancer two, second malignancies nine, cardiovascular disease eight, trauma two, and pulmonary one).ConclusionsIn this cohort of prostate brachytherapy patients, Agent Orange exposure did not statistically impact survival in multivariate analysis.     

An age-corrected matched-pair study of erectile function in patients treated with dose-escalated adaptive image-guided intensity-modulated radiation therapy vs. high-dose-rate brachytherapy for prostate cancer

PurposeTo compare erectile dysfunction (ED) after adaptive dose-escalated image-guided intensity-modulated radiotherapy (IG-IMRT) and high-dose-rate interstitial brachytherapy (HDR) monotherapy.Methods and MaterialsLow- and intermediate-risk prostate cancer patients treated with IG-IMRT or HDR were matched on pretreatment ED, age, Gleason score, T-stage, and prostate specific antigen. Patients who received androgen deprivation therapy were excluded. ED was graded by Common Terminology Criteria for Adverse Events v4. Actuarial rates of ED were computed by the Kaplan–Meier method.ResultsThere were 384 patients with median followup of 2.0 years (0.5–6.1) for IG-IMRT and 2.0 years (0.5–8.7) for HDR. The median IG-IMRT dose was 75.6 Gy and HDR dose 38 Gy in four fractions. For patients with no pretreatment ED, actuarial rates of requiring intervention (Grade ≥2 ED) at 3 years were 31% for IG-IMRT and 19% for HDR (p = 0.23), and impotence despite medical intervention (Grade 3) were 0% for IG-IMRT and 6% for HDR (p = 0.06). For patients with Grade 1 pretreatment ED, Grade ≥2 ED at 3 years were 47% for IG-IMRT and 34% for HDR (p = 0.79), and Grade 3 ED were 15% in both groups (p = 0.59). For patients with Grade 2 pretreatment ED, Grade 3 ED at 3 years were 22% for IG-IMRT and 37% for HDR (p = 0.70). No variables were predictive of Grade ≥2 ED following treatment.ConclusionsRates of ED requiring medical intervention for both IG-IMRT and HDR are low and equivalent. Even patients with ED before treatment are likely to maintain potency with medication use at 3 years following treatment.     

The impact of perineural invasion on biochemical outcome after permanent prostate iodine-125 brachytherapy

PurposePerineural invasion (PNI) in prostate biopsies is associated with increased risk of higher Gleason score and worse pathologic stage. We report the influence of PNI in biochemical no evidence of disease (bNED) survival after ¹²⁵I prostate brachytherapy (BT).Methods and MaterialsPathology reports of 700 men with localized prostate cancer who underwent ¹²⁵I prostate BT in 1999–2008 were reviewed. The presence or absence of PNI in the biopsy was documented in 339 men. Clinical, treatment, and dosimetric parameters, along with PNI status, were evaluated for bNED survival, defined by “nadir + 2” definition.ResultsOf the 339 patients, 87% had favorable risk and 13% intermediate risk. PNI was present in 89 patients (26%). After a median followup of 32 months, there were five biochemical failures (4: +PNI and 1: ?PNI), of which one was local failure (+PNI). Actuarial 5-year bNED survival for the entire group was 97.0% (92.9% for +PNI; 99.2% for ?PNI). In univariate analysis age, pretreatment prostate-specific antigen, Gleason score 7, and intermediate risk group predicted for worse biochemical outcome, whereas the presence of PNI showed a trend toward significance (p = 0.06). Some of the regression algorithms failed to converge because of low event rates.ConclusionsWe report excellent biochemical control in 339 men treated with ¹²⁵I prostate BT. The presence of PNI showed a trend toward significance in predicting 5-year bNED survival but did not impact on local control and should not influence the decision to recommend BT for localized prostate cancer.     

Brachytherapy provides comparable outcomes and improved cost-effectiveness in the treatment of low/intermediate prostate cancer

PurposeTo evaluate the cost-effectiveness and outcomes of low-dose-rate (LDR) and high-dose-rate (HDR) brachytherapy compared with intensity-modulated radiation therapy (IMRT) in patients with low/intermediate risk of prostate cancer.Methods and MaterialsOne thousand three hundred twenty-eight patients with low or intermediate risk of prostate cancer were treated with LDR (n = 207), HDR with four fractions (n = 252), or IMRT (n = 869) between January 1992 and December 2008. LDR patients were treated with palladium seeds to a median dose of 120 Gy, whereas HDR patients were treated to a median dose 38.0 Gy (four fractions). IMRT patients received 42–44 fractions with a median dose of 75.6 Gy. Clinical outcomes were compared, including biochemical failure, cause-specific survival, and overall survival.ResultsOverall, no differences in 5-year biochemical control (BC) or cause-specific survival were noted among treatment modalities. The calculated reimbursement for LDR brachytherapy, HDR brachytherapy with four fractions, and IMRT was $9,938; $17,514; and $29,356, respectively. HDR and LDR brachytherapy were statistically less costly to Medicare and the institution than IMRT (p < 0.001), and LDR brachytherapy was less costly than HDR brachytherapy (p = 0.01 and p < 0.001). Incremental cost-effectiveness ratios for cost to Medicare for BC with IMRT were $4045 and $2754 per percent of BC for LDR and HDR brachytherapy, respectively. Incremental cost-effectiveness ratio using institutional cost comparing IMRT with LDR and HDR brachytherapy was $4962 and $4824 per 1% improvement in BC.ConclusionsIn this study of patients with low and intermediate risk of prostate cancer, comparable outcomes at 5 years were noted between modalities with increased costs associated with IMRT.     

Prognostic importance of tobacco use in men receiving definitive prostate brachytherapy

PurposeSeveral prominent publications have identified an overall association between tobacco use and an increased risk of disease recurrence and disease-specific mortality in prostate cancer patients. The authors explored whether tobacco use adversely impacts treatment outcomes in men treated with permanent interstitial brachytherapy.Methods and MaterialsFrom April 1995 to August 2008, 2057 patients underwent brachytherapy by a single brachytherapist. Median follow-up was 7.5 years. The role of tobacco use as a prognostic factor for biochemical progression-free survival, cause-specific survival, and overall survival was investigated. Differences in survival between smokers and nonsmokers were compared using Kaplan–Meier curves and log-rank tests.ResultsCurrent smokers presented with a lower body mass index (p < 0.001), smaller prostate size (p = 0.003), younger age (p < 0.001), higher prostate-specific antigen level (p = 0.002), a trend toward higher percentage biopsy core involvement (p = 0.08), higher incidence of perineural invasion (p = 0.015), and higher risk disease (p < 0.001) than former or nonsmokers. There was no difference in biochemical progression-free survival (p = 0.30) or cause-specific survival (p = 0.72) at 10 years for smokers compared with nonsmokers. On univariate and multivariate analysis, tobacco use was an adverse risk factor for overall survival (p < 0.001). There was no association between smoking and any prostate cancer-specific outcome.ConclusionsSmokers treated with brachytherapy have excellent outcomes and are at no higher risk of treatment failure than men who are nonsmokers.     

High-dose-rate brachytherapy in combination with conformal external beam radiotherapy in the treatment of prostate cancer

PurposeTo report long-term outcomes for treatment of prostate cancer using dose escalation with high-dose-rate (HDR) brachytherapy and 3-dimensional conformal external beam radiotherapy (3DCRT), and compare them with outcomes for treatment of prostate cancer with 3DCRT alone at the same institution.Methods and MaterialsFrom 1998 to 2003, 587 patients were treated for clinically localized prostate cancer. Patients received either 3DCRT (median, 46 Gy) with a single HDR brachytherapy implant (196 patients) delivering a fractionated dose of 18 Gy (combined group) or 3DCRT (median, 70 Gy; 387 patients; “3DCRT alone”). There were 41.9% patients with intermediate-risk and 42.6% with high-risk disease. In all, 441 patients (75.1%) received neoadjuvant and 116 patients (19.8%) received adjuvant androgen deprivation therapy. The American Society of Therapeutic Radiology and Oncology Phoenix definition for biochemical failure was used.ResultsThe median followup was 5.5 years. The 5- and 7-year biochemical control (BC) rates were 82.5% and 80.3%, respectively, for the combined group and 81.3% and 71%, respectively, for 3DCRT alone; for overall survival, they were 91.9% and 89.5% vs. 88.7% and 86.2%, respectively, whereas for cause-specific survival, they were 96.9% and 96.1% vs. 97.6% and 96.2%, respectively. Cox proportional hazard regression analysis for BC revealed that low Gleason grade, HDR brachytherapy combined with 3DCRT, and adjuvant androgen deprivation therapy were significant in predicting BC. Radiation Therapy Oncology Group Grade 3 late urinary and rectal morbidity rates were 7.1% and 0%, respectively. No Grade ≥4 reactions were detected.ConclusionsHDR brachytherapy combined with 3DCRT was associated with improved BC and minimal toxicity in patients with unfavorable prostate cancer compared with conventional 3DCRT.     

Brachytherapy for penile cancer: Efficacy and impact on sexual function

PurposePenis brachytherapy (PB) remains an alternative in the cancer treatment. The objective of this study was to assess the oncologic outcomes, sexual function, and the sexual behavior of men treated by PB for a cancer of the penis.Methods and MaterialsBetween 1992 and 2009, 47 patients with a cancer of the penis were treated by PB (¹⁹²Ir), in the Toulouse, Montpellier, and Barcelona cancer centers. The investigation into their sexuality was obtained by means of questionnaire. A total of 21 French patients were approached, of whom 19 (mean age = 73.2 years) agreed to answer the questionnaire (participation rate = 90.5%).ResultsOncologic data: The specific survival and the disease-free survival at 5 years was 87.6% (95% confidence interval, 72.4–94.7%) and 84% (95% confidence interval, 57.6–94.7%), respectively. The rate of preservation of the penis was 66% (n = 31). Sexual data: Among the 17 patients sexually active before brachytherapy, 10 patients remained sexually active after treatment (58.8%). Of the 18 patients who had erections before PB, 17 still had them after treatment (94.4%). Age was the main predictive factor.ConclusionThe PB seems to have a moderated impact on the sexual functions and the sexual behavior of the patients.     

Long-term outcome for prostate cancer using pseudo pulse–dosed rate brachytherapy,external beam radiotherapy,and hormones

PurposeWe report the long-term outcomes of pulse-dose rate (PDR) brachytherapy used in a nonstandard style (pseudo-PDR) with an high-dose rate brachytherapy technique in conjunction with external beam radiotherapy (EBRT) and hormonal manipulation on prostate cancer (PC).Methods and MaterialsWe treated 253 patients with Stage T1–T3 N0M0 PC, between December 1999 and March 2006. All patients received neoadjuvant androgen deprivation for a median 6 months. Treatment consisted of three pulses of pseudo-PDR brachytherapy to a median dose of 18 Gy with 50.4 Gy in 28 fractions of EBRT.ResultsAt a median 6 years followup, (range, 1–11 years), 5-year overall survival was 92%, and PC-specific survival was 96%. The 5-year biochemical control (biochemical no evidence of disease) by the Phoenix definition for low-, intermediate-, and high-risk groups was 95%, 90%, and 71%, respectively (p < 0.00001). At 6 years, the incidence of Radiotherapy Oncology Group Grade 2 and 3 genitourinary toxicity was 1% and 6%; Radiotherapy Oncology Group Grade 2 and 3 gastrointestinal toxicity was 4% and 0%. Erectile preservation at 3 years was 58%. The Phoenix definition best predicted clinical failure with a high specificity (94%).ConclusionsPseudo-PDR brachytherapy plus EBRT with limited neoadjuvant hormonal manipulation is an effective treatment option in localized PC, with minimal and tolerable morbidity and provides excellent control. This technique of a modified PDR-delivery technique appears as effective as high-dose rate therapy.     

Re-irradiation with interstitial pulsed-dose-rate brachytherapy for unresectable recurrent head and neck carcinoma

PurposeTo assess the long-term results of protocol-based interstitial pulsed-dose-rate (PDR) brachytherapy combined with simultaneous chemotherapy in selected patients with recurrent head and neck tumors not amenable to salvage surgery.Methods and MaterialsA total of 51 patients with recurrent head and neck cancer were treated with interstitial PDR brachytherapy. Forty patients (78%) had salvage brachytherapy alone using a median total dose of 60 Gy. Salvage brachytherapy in combination with external beam therapy was performed in 11 patients (22%) using a median total dose of D_REF = 27 Gy. Simultaneously with the PDR brachytherapy, a concomitant chemotherapy was administered in 35/51 (69%) of patients. The analysis was performed after a median followup of 58 months.ResultsLocal control rates calculated according to Kaplan–Meier after 2 and 5 years were 71% and 57%, respectively. Comparing results of salvage PDR brachytherapy with or without simultaneous chemotherapy, the 5-year local recurrence-free survival rates were 78.9% vs. 38.5% (p = 0.01), respectively. No other patient or treatment-related parameters had a significant influence on treatment results. A total of 9/51 (17.7%) and 6/51 (11.8%) patients developed soft-tissue necrosis or bone necrosis, respectively, but only 2% of patients required surgical treatment.ConclusionsPDR interstitial brachytherapy with pulse doses between 0.4 and 0.7 Gy/h/24 h with simultaneous chemotherapy is an effective and safe option for curative therapy in selected patients with head and neck cancer in previously irradiated areas, which are not suitable for salvage surgery.     

Four-year outcomes of hypofractionated high-dose-rate prostate brachytherapy and external beam radiotherapy

PurposeHigh-dose-rate (HDR) brachytherapy boost in prostate cancer allows dose escalation and delivery of higher biologically effective dose (BED). We evaluated the outcomes of intensity-modulated radiation therapy (IMRT) and HDR boost in a community setting.Methods and MaterialsBetween July 2003 and April 2008, 148 patients with prostate cancer were treated at Cancer Center of Irvine using two transperineal implants performed 1 week apart (22 Gy delivered in four fractions divided between two insertions and delivered twice daily), followed by IMRT (50.4 Gy). Hormonal therapy was given for 1 year to all patients with Gleason score of 8 or higher.ResultsPatient characteristics are as follows: median age at treatment, 71 years; American Joint Committee on Cancer Group IIB, 53%; Gleason score of 7, 41%; and Gleason score of 8 or higher, 14%. Median followup was 49 months, and median prostate-specific antigen (PSA) nadir was 0.15 ng/mL. The 4-year actuarial biochemical disease-free survival (bDFS) was 96.8/81% by Phoenix/PSA lower than 0.5 ng/mL criteria. According to National Comprehensive Cancer Center Clinical Practice Guidelines–defined recurrence risk groups, 4-year bDFS for low risk was 100/92.9%, intermediate risk was 100/86.7%, and high risk was 94/75.4% by Phoenix/PSA lower than 0.5 ng/mL criteria. No statistically significant difference in bDFS was detected by either failure criteria based on risk group, lymph node risk, or initial PSA. Treatment was well tolerated. Subacute/late genitourinary and gastrointestinal toxicities were limited to 10% and 5%, respectively of all patients.ConclusionsProstate IMRT plus HDR brachytherapy boost was well tolerated with appropriate PSA response and bDFS at 4 years, demonstrated in a community setting. This treatment schema provides a high BED, comparable with hypofractionated prostate regimens previously reported in the literature. Higher BED delivery should be explored in further dose escalation studies.     

Prostate brachytherapy in men with gland volume of 100 cc or greater: Technique,cancer control,and morbidity

PurposeTo determine the outcomes of prostate seed implantation in men with prostate volume (PV) of 100 cc or greater (PV100).MethodsA total of 2051 men with localized prostate cancer were treated with permanent prostate brachytherapy of whom 34 (1.7%) had PV100 (mean, 126.2; range, 100–205 cc). The PV100 patients were older (mean, 69 vs. 66 years; p = 0.031), had higher initial prostate-specific antigen level (20.4 vs. 9.6 ng/mL, p < 0.001), and received a lower dose (182 vs. 194 Gy₂ biologic equivalent dose, p = 0.032). There were no differences in clinical stage, Gleason score, and baseline International Prostate Symptom Score. The mean followup time was 6.7 years (range, 2–18). Biochemical freedom from failure (bFFF) was defined using the Phoenix definition.ResultsThe BFFF at 10 years was no different between PV100 and smaller glands (82.4% vs. 84.5%, p = 0.71). At last followup, mean International Prostate Symptom Score for PV100 increased from 8.5 to 9.1 against 7.4 to 9.2 for smaller glands (p = 0.935). Urinary retention rates were higher for PV100 (6/34, 17.6% vs. 148/2017, 7.3%; odds ratio, 2.71; 95% confidence interval, 1.1–6.6; p = 0.038). Postimplant transurethral resection of the prostate was performed in none of the 34 patients with PV100 against 66 of the 2017 patients (3.3%, p < 0.001). Long-term radiation proctitis for PV100 were 1 of 34 (2.9%) against 82 of 2017 (4.1%, p = 0.741). Rectourethral fistula occurred in 4 patients (0.19%), that is, 1 of 34 (2.9%) in PV100 group and 3 of 2017 (0.1%, p < 0.001).ConclusionThis study demonstrates the feasibility of implanting patients with PV100. Very large PV does not influence bFFF. Although urinary retention rates were higher, the long-term urinary symptoms were no different between the two groups. Requirement for transurethral resection of the prostate was no higher in patients with PV100. Radiation proctitis rates were similar for both.     

PSA bounce after prostate brachytherapy with or without neoadjuvant androgen deprivation

PurposeTo assess the impact of PSA bounce (PB) on biochemical failure (BF) and clinical failure (CF) in brachytherapy patients treated with or without neoadjuvant androgen deprivation (AD).Methods and MaterialsFrom 1987 to 2003, 691 patients with clinical stage T1–T3N0M0 prostate cancer were treated with external beam radiotherapy (EBRT) and high-dose-rate (HDR) brachytherapy boost (n = 407), HDR brachytherapy alone (n = 93), or permanent seed implant (n = 191). Three hundred seventeen patients (46%) received neoadjuvant/adjuvant AD with RT. BF was scored using 3 definitions (ASTRO—3 rises, nadir + 2 ng/ml, and threshold 3 ng/ml) based on current and absolute nadir (AN) methodologies. PB was defined as any increase in PSA followed by a decrease to the prior baseline or lower. The median followup was 4.0 years.ResultsForty-six patients (7%) experienced CF at 5 years. PB of ≥0.1, ≥1.0, and ≥2.0 ng/ml at any time after RT occurred in 330 (48%), 60 (9%), and 22 patients (3%) respectively. The use of an AN definition reduced the likelihood of scoring PB as BF across all levels. The patients receiving AD experienced significantly longer bounce duration. Bounce <1.0 ng/ml showed no association with CF. For bounce ≥1.0 ng/ml, 10% demonstrated CF vs. 6% without bounce of this amplitude (p = 0.27). Bounces ≥1.0 ng/ml were more likely to be scored as BFs for definitions based on current nadir (3 rises: 20% vs. 13%, nadir + 2: 43% vs. 11%, 3 at/after nadir: 57% vs. 12%) than those based on AN (3 rises: 8% vs. 10%, nadir + 2: 18% vs. 11%, 3 at/after nadir: 13% vs. 11%).ConclusionsBounces ≥1.0 ng/ml are rare after brachytherapy with or without neoadjuvant AD, occurring in less than 10% of patients. Low PBs have little impact on BF, but as PB amplitude increases, the BF rate increases. BF definitions based on AN are less sensitive to PB after brachytherapy.