Long-term outcomes of prostate cancer patients with Gleason pattern 5 treated with combined brachytherapy and external beam radiotherapy

PurposeRecent reports have suggested relatively poor prognosis for prostate cancer patients with Gleason pattern 5 treated with dose-escalated external beam radiotherapy (XRT) and androgen deprivation therapy (ADT). We present the largest series of men with high-risk, Gleason pattern 5 prostate cancer treated with permanent interstitial brachytherapy and XRT.Methods and MaterialsBetween April 1995 and December 2008, 329 consecutive patients with National Comprehensive Cancer Network high-risk disease were treated with permanent interstitial brachytherapy. Most received XRT and ADT. Median followup was 7.2 years. The cause of death was determined for each deceased patient. Multiple clinical, treatment, and dosimetric parameters were evaluated for impact on the evaluated survival parameters.ResultsAt 10 years, biochemical progression-free survival, cause-specific survival (CSS), and overall survival for the group of high-risk patients as a whole was 91.1%, 95.5%, and 72.5%, respectively. There was no difference in biochemical progression-free survival between men with and without Gleason pattern 5 (89.7% vs. 91.8%; p = 0.56). However, men with Gleason pattern 5 had lower prostate cancer CSS (90.3% vs. 98.1%; p = 0.011). There was no difference in overall survival comparing men with and without Gleason pattern 5 disease (67.7% vs. 75.4%; p = 0.14).ConclusionsMen with high-risk, Gleason pattern 5 histology treated with brachytherapy and XRT have excellent long-term outcomes, which compare favorably to dose-escalated XRT/ADT series without brachytherapy. Nonetheless, Gleason pattern 5 results in lower CSS than high-risk disease without Gleason pattern 5.     

Famotidine as a radioprotector for rectal mucosa in prostate cancer patients treated with radiotherapy

Background and purpose

Acute bowel toxicity significantly affects the quality of life of patients treated with pelvic radiotherapy. This study was performed to assess whether pretreatment with famotidine can reduce acute radiation toxicities in patients undergoing radiotherapy for prostate cancer.

Patients and methods

Between April 2012 and February 2013, 36 patients undergoing radiotherapy for prostate cancer were enrolled to receive either placebo or famotidine. The patients received external-beam radiotherapy up to 70 Gy at daily fractions of 1.8–2 Gy (5 days/week). Oral famotidine 40 mg (80 mg/day) or placebo was administered twice daily (4 and 3 h prior to each radiotherapy fraction). Bowel and bladder acute toxicities were evaluated weekly during radiotherapy and once thereafter according to RTOG grading criteria.

Results

Famotidine was well tolerated. No grade III or higher acute toxicities were noted in the two groups. Grade II rectal toxicity developed significantly more often in patients receiving placebo than in patients receiving famotidine (10/18 vs. 2/16, p?=?0.009). Moreover, no rectal bleeding occurred in the famotidine group, while 5 patients in the placebo group experienced rectal bleeding during treatment (p?=?0.046). The duration of rectal toxicity in the radiotherapy course was also reduced in the famotidine group (15.7 vs. 25.2 days, p?=?0.027). No significant difference between the two groups was observed in terms of urinary toxicity.

Conclusion

We demonstrated for the first time that famotidine significantly reduces radiation-induced injury on rectal mucosa representing a suitable radioprotector for patients treated with radiotherapy for prostate cancer.     

Adaptive off-line protocol for prostate external radiotherapy with cone beam computer tomography

Purpose

The goal of this work was to prepare and to evaluate an off-line adaptive protocol for prostate teleradiotherapy with kilovoltage cone beam computer tomography (CBCT).

Patients and methods

Ten patients with localized prostate carcinoma treated with external beams underwent image-guided radiotherapy. In total, 162?CBCT images were collected. Position of prostate and pubis symphysis (PS) with respect to the isocenter were measured off-line. Using the CBCT scans obtained in the first three fractions the average position of prostate in relation (AvPosPr) to PB was calculated. On each CBCT scan, the position of prostate with respect to AvPosPr was calculated and cumulative histogram of prostate displacement with respect to AvPosPr was prepared. Using this data, the adaptive protocol was prepared in which (1) based on the CBCT made in the first three fractions the AvPosPr to PS is obtained, (2) in all other fractions two orthogonal images are acquired and if for any direction set-up error exceeds 0.2?cm the patient’s position is corrected, and (3) additionally, the patient’s position is corrected if the AvPosPr exceeds 0.2?cm in any direction. To evaluate the adaptive protocol for 30?consecutive patients, the CBCT was also made in 10th and 21st fraction.

Results

For the first 10?patients, the results revealed that the prostate was displaced in relation to AvPosPr >0.7?cm in the vertical and longitudinal directions only on 4 and 5?images of 162?CBCT images, respectively. For the lateral direction, this displacement was >0.3?cm in one case. For the group of 30?patients, displacement was never >0.7, and 0.3?cm for the vertical and lateral directions. In two cases, displacements were >0.7?cm for the longitudinal direction.

Conclusion

Implementation of the proposed adaptive procedure based on the on-line set-up error elimination followed by a reduction of systematic internal error enables reducing the CTV–PTV margin to 0.7, 0.7, and 0.4?cm for the vertical, longitudinal, and lateral directions, respectively.     

Primary rectal cancer treated with high-dose-rate intraluminal brachytherapy following external radiotherapy

An 80-year-old man with rectal cancer who had diabetes and angina was treated with high-dose-rate intraluminal brachytherapy (30 Gy) following external radiotherapy (30 Gy). After this treatment, anal pain and bleeding improved greatly, and he was able to evacuate the bowels. However, the endoscopic biopsy taken five months after treatment revealed active cancer cells.     

Assessing the impact of brachytherapy boost and androgen deprivation therapy on survival outcomes for patients with unfavorable intermediate-risk prostate cancer patients treated with external beam radiotherapy

BACKGROUNDCurrent recommendations regarding radiotherapy treatment for unfavorable intermediate-risk prostate cancer (UIR-PCa) include external beam radiotherapy (EBRT) ± brachytherapy boost (BT) ± androgen deprivation therapy (ADT). The ideal radiotherapy treatment approach for UIR-PCa has not been well-defined. We hypothesized that EBRT+BT±ADT is associated with improved overall survival (OS) relative to EBRT±ADT in men with UIR-PCa.MATERIALS AND METHODSThe National Cancer Database (NCDB) was used to retrospectively identify 32,246 men diagnosed between 2004 and 2015 with UIR-PCa who received EBRT (n = 13,265), EBRT+ADT (n = 13,123), EBRT+BT (n = 3440), or EBRT+BT+ADT (n = 2418). OS was the primary outcome. Inverse probability of treatment weighting was used to adjust for covariable imbalances and weight-adjusted multivariable analysis using Cox regression modeling was used to compare OS hazard ratios.RESULTSMedian follow-up was 60 months (range: 3–168 months). EBRT+ADT correlated with improved OS relative to EBRT alone on multivariable analysis (Hazard Ratio (HR): 0.92, [95% Confidence Interval: 0.87–0.98], p = 0.005). Compared to EBRT+ADT, EBRT+BT (HR: 0.77 [0.69–0.85], p = 3 × 10^?7) and EBRT+BT+ADT (HR: 0.75 [0.67–0.83], p = 6 × 10^?8) were associated with improved OS. Eight-years OS for the EBRT+ADT versus EBRT+BT+ADT was 70% and 78% (p < 0.0001), which is similar to historical clinical trials (ASCENDE-RT 9-year OS: 74% vs. 78%, p = 0.29). Relative to EBRT+BT, EBRT+BT+ADT was not associated with improved OS (HR: 0.99 [0.87–1.11], p = 0.82).CONCLUSIONSIn a large retrospective cohort, the addition of brachytherapy to EBRT correlated with improved survival in men with UIR-PCa. Men receiving EBRT+ADT+BT had improved OS relative to EBRT+ADT. The addition of ADT to EBRT, but not to EBRT+BT, correlated with improved OS.     

Localized prostate cancer with intermediate- or high-risk features treated with combined external beam radiotherapy and iodine-125 seed brachytherapy

ObjectiveThe aim of the study is to compare the results of the combined external beam radiotherapy (EBRT) with iodine-125 seed brachytherapy vs. brachytherapy alone for prostate cancer treatment in patients with intermediate and high risk of disease recurrence.Methods and MaterialsNinety-six patients were treated from January 1998 to December 2006. Twenty-four patients received combined treatment and 72 patients received brachytherapy alone. Patients were classified into intermediate or high risk of recurrence according to the D’Amico’s classification. The prescribed dose for brachytherapy was 145 Gy as monotherapy and 110 Gy for combined treatment. The dose of EBRT was 45 Gy over 5 weeks, with 1.8 Gy daily fractions. Results were analyzed based on Phoenix definition of biochemical recurrence, that is, nadir plus 2 ng/mL.ResultsBiochemical control was achieved by 96% (23 of 24) of patients receiving combined treatment and by 72% (52 of 72) in the group treated by brachytherapy alone (p < 0.015). The addition of EBRT resulted in a 94% biochemical disease-free survival at 5 years; and in brachytherapy alone group, the rate was 54% (p < 0.011). Mean followup was 96 months (24–132 months; confidence interval 95%: 90–102).ConclusionThis study shows that in patients with localized prostate cancer, with intermediate and high risk of biochemical recurrence, the addition of EBRT can confer a significant biochemical control advantage when added to brachytherapy.     

Physical and clinical implications of radiotherapy treatment of prostate cancer using a full bladder protocol

Purpose

To assess the dosimetric and clinical implication when applying the full bladder protocol for the treatment of the localized prostate cancer (PCA).

Patients and Methods

A total of 26 consecutive patients were selected for the present study. Patients underwent two series of CT scans: the day of the simulation and after 40 Gy. Each series consisted of two consecutive scans: (1) full bladder (FB) and (2) empty bladder (EB). The contouring of clinical target volumes (CTVs) and organs at risk (OAR) were compared to evaluate organ motion. Treatment plans were compared by dose distribution and dose?Cvolume histograms (DVH).

Results

CTV shifts were negligible in the laterolateral and superior?Cinferior directions (the maximum shift was 1.85 mm). Larger shifts were recorded in the anterior?Cposterior direction (95% CI, 0.83?C4.41 mm). From the dosimetric point of view, shifts are negligible: the minimum dose to the CTV was 98.5% (median; 95%CI, 95?C99%). The potential advantage for GU toxicity in applying the FB treatment protocol was measured: the ratio between full and empty bladder dose?Cvolume points (selected from our protocol) is below 0.61, excluding the higher dose region where DVHs converge.

Conclusion

Having a FB during radiotherapy does not affect treatment effectiveness, on the contrary it helps achieve a more favorable DVH and lower GU toxicities.     

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.     

Transperineal gold marker implantation for image-guided external beam radiotherapy of prostate cancer

Purpose

To present the feasibility and complications of transperineal fiducial marker implantation in prostate cancer patients undergoing image-guided radiotherapy (IGRT)

Methods and materials

Between November 2011 and April 2016, three radiopaque, gold-plated markers were transperineally implanted into the prostate of 300 patients under transrectal ultrasound guidance and with local anaesthesia. A week after the procedure patients filled in a questionnaire regarding pain, dysuria, urinary frequency, nocturia, rectal bleeding, hematuria, hematospermia or fever symptoms caused by the implantation. Pain was scored on a 1–10 scale, where score 1 meant very weak and score 10 meant unbearable pain. The implanted gold markers were used for daily verification and online correction of patients’ setup during IGRT.

Results

Based on the questionnaires no patient experienced fever, infection, dysuria or rectal bleeding after implantation. Among the 300 patients, 12 (4%) had hematospermia, 43 (14%) hematuria, which lasted for an average of 3.4 and 1.8 days, respectively. The average pain score was 4.6 (range 0–9). Of 300 patients 87 (29%) felt any pain after the intervention, which took an average of 1.5 days. None of the patients needed analgesics after implantation. Overall, 105 patients (35%) reported less, 80 patients (27%) more, and 94 patients (31%) equal amount of pain during marker implantation compared to biopsy. The 21 patients who had a biopsy performed under general anesthesia did not answer this question.

Conclusion

Transperineal gold marker implantation under local anesthesia was well tolerated. Complications were limited; rate and frequency of perioperative pain was comparable to the pain caused by biopsy. The method can be performed safely in clinical practice.

     

A technique to re-establish dose distributions for previously treated brain cancer patients in external beam radiotherapy.

Tumor recurrences or new tumors may develop after irradiation of local lesion(s) in the brain, and additional radiotherapy treatments are often needed for previously treated patients. It is critical to re-establish the dose distributions delivered during the previous treatment in the current patient geometry, so that the previous dose distributions can be accurately taken into consideration in the design of the current treatment plan. The difficulty in re-establishing the previous treatment dose distributions in the current patient geometry arises from the fact that the patient position at the time of reirradiation is different from that at the previous treatment session. Simple re-entry of the previous isocenter coordinates, gantry, and couch and collimator angles into the new treatment plan would result in incorrect beam orientations relative to the new patient anatomy, and therefore incorrect display of the previous dose distributions on the current patient anatomy. To address this issue, a method has been developed so that the previous dose distributions can be accurately re-established in the framework of the current brain treatment. The method involves 3 matrix transformations: (1) transformation of beams from machine coordinate system to patient coordinate system in the previous treatment; (2) transformation of beams from patient coordinate system in the previous treatment to patient coordinate system in the current treatment; and (3) transformation of beams from patient coordinate system in the current treatment to machine coordinate system. The transformation matrices used in the second transformation are determined by registration using a mutual information-based algorithm with which the old and new computed tomography (CT) scan sets are registered automatically without human interpretation. A series of transformation matrices are derived to calculate the isocenter coordinates, the gantry, couch, and collimator angles of the beams for the previous treatment in the current patient geometry, and the previous dose distributions are re-established on the current CT images. The method has been proven to be successful and robust.     

Base-of-tongue cancer treated with external beam irradiation plus brachytherapy: oncologic and functional outcome.

Between January 1981 and June 1990, 36 previously untreated patients with squamous cancer of the base of the tongue were treated with radiation therapy. This therapy consisted of a 5,000-5,400-cGy external beam plus a 2,000-3,000-cGy boost to the base of the tongue with an iridium-192 implant. Necks with negative nodes were only irradiated, while necks with positive nodes were treated with irradiation plus neck dissection. Actuarial local control and survival at 2 years were 87.5%. Neck control was achieved in 35 of 36 patients. When implantation was performed with the nonlooping technique, the injury rate was statistically higher than in patients who underwent implantation with the looping technique (P = .02). Thirty patients participated in a function assessment involving a Performance Status Scale for patients with head and neck cancer. The authors concluded that management of base-of-tongue cancer with external beam irradiation plus brachytherapy is both oncologically and functionally successful.     

乳腺癌保乳术后放射治疗的疗效观察

目的观察乳腺癌保乳术后放射治疗的疗效和美观效果。方法109例保乳术后在我科接受全乳外照射和瘤床加量(boost)放疗,79例应用高剂量率插植技术,T1肿瘤用单排插植,针距为1.5cm,T2以上肿瘤用双排或三排插植。针距间单次剂量(DB)10～12Gy,靶区周边剂量为85%DB。30例采用电子线常规外照射15Gy。全乳照射应用6MV直线加速器,采用双切线半野照射技术,靶区剂量为45～52Gy(平均48.6Gy)。采用医生评分与患者问卷方法评价美观效果。结果全组109例应用KaplanMeier方法统计5年实际生存率为93.8%。局部复发率为6.5%。全组无放射性溃疡发生,5例出现位于插植针孔周围急性皮肤炎症。在经临床随访体检的75例中,医生打分和患者自评满意度为优的比例分别为87%和81%,无统计学意义(P>0.05)。48例经组织间插植加量放疗;27例经电子线外照加量放疗。两组满意度医生总评为优的患者比例分别为81.2%和85.2%,差异无统计学意义(P>0.05)。结论乳腺癌保乳术后放疗可降低局部复发率,并发症少。不同的瘤床加量放疗方法不影响美观效果。