Salvage radiotherapy after cryotherapy in prostate cancer.

Can Early Implementation of Salvage Radiotherapy for Prostate Cancer Improve the Therapeutic Ratio? A Systematic Review with Radiobiological Modeling

Hodgkin-Lymphoma with Relapsed or Progressive Disease after Autologous Stem Cell Transplantation: Efficacy of Salvage Radiation Therapy

Objective: to evaluate the effectiveness of salvage radiotherapy in patients with recurrent prostate cancer after radical prostatectomy. Materials and methods. In the period from March 2009 to January 2015, 92 patients with prostate cancer and biochemical recurrences after radical prostatectomy underwent salvage radiotherapy with classic fractionation and hypofractionation of the radiation dose. Results and conclusion. Median follow-up duration was 40 months (12–78 months). Overall survival was 100 %. Local control was 100 %. One (1), 2, and 3-year disease-free survival in the whole patient group was 96, 91, and 86 %; in the hypofractionation group it was 98, 95, and 89 %; in the classical fractionation group it was 95, 87, and 84 %, respectively. We have determined that the period of doubling of prostate-specific antigen level of ≤6 months (p = 0.035) after surgical treatment and prostate-specific antigen level >0.5 ng/ml (p = 0.037) at the time of salvage radiotherapy are significantly associated with worse prognosis for treatment effectiveness. There weren’t any differences in late toxicity between the 2 patient groups.

Phase II Randomized Study of Salvage Radiation Therapy (SRT) plus Enzalutamide or Blinded Placebo for High-Risk PSA-Recurrent Prostate Cancer after Radical Prostatectomy: The SALV-ENZA Trial

To evaluate the clinical outcome in men with recurrent prostate cancer (PCa) treated by salvage radiotherapy (sRT) prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA PET/CT)-guided. From January 2021 to January 2023, 33 patients who previously underwent definitive/systemic therapy were submitted to sRT PSMA PET/CT-guided for PCa recurrence: 16 (48.5%) on the prostate bed (PB), 12 (36.4%) on the lymph node (LN) and five (15.1%) on the bone. The median PSA value was 3.3 ng/ml (range=0.3-15.5 ng/ml): 0.2-0.5 ng/ml (18.2% cases), 0.51-1 ng/ml (39.4% cases) and >1 ng/ml (42.4% cases). Median 18F PSMA PET/CT standardized uptake value (SUVmax) was evaluated on PB, vs. LN vs. bones PCa recurrences and was equal to 12.5 vs. 19.0 vs. 30.1, respectively. Overall, at a median follow up of 12 months, 23/33 patients (69.7%) had local control without distant progression (PSA and SUVmax evaluation): 14/16 (87.5%) vs. 7/12 (58.3%) vs. 2/5 (40%) underwent sRT on the PB vs. LN vs. bone metastases, respectively. PSMA PET/CT allows to perform sRT early in men with PCa recurrence and low PSA values obtaining a complete clinical response in approximately 70% of the cases one year from treatment.

ABSTRACTPurpose:To compare the treatment outcomes of a cohort of prostate cancer patients treated with conventional schedule using IMRT or 3DRT technique.Materials and Methods:Between 2010-2017, 485 men with localized prostate cancer were treated with conventional radiotherapy schedule with a total dose ≥74Gy using IMRT (231) or 3DCRT (254). Late gastrointestinal (GI) and genitourinary (GU) toxicity were retrospectively evaluated according to modified RTOG criteria. The biochemical control was defined by the Phoenix criteria (nadir + 2ng/mL). The comparison between the groups included biochemical recurrence free survival (bRFS), overall survival (OS) and late toxicity.Results:With a median follow-up of 51 months (IMRT=49 and 3DRT=51 months), the maximal late GU for >=grade- 2 during the entire period of follow-up was 13.1% in the IMRT and 15.4% in the 3DRT (p=0.85). The maximal late GI ≥ grade- 2 in the IMRT was 10% and in the 3DRT 24% (p=0.0001). The 5-year bRFS for all risk groups with IMRT and 3D-CRT was 87.5% vs. 87.2% (p=0.415). Considering the risk-groups no significant difference for low-, intermediate- and high-risk groups between IMRT (low-95.3%, intermediate-86.2% and high-73%) and 3D-CRT (low-96.4%, intermediate-88.2% and high-76.6%, p=0.448) was observed. No significant differences for OS and DMFS were observed comparing treatment groups.Conclusion:IMRT reduces significantly the risk of late GI severe complication compared with 3D-CRT using conventional fractionation with a total dose ≥74Gy without any differences for bRFS and OS.

e18502 Background: Ocular adnexal mucosal associated lymphoid tissue lymphomas (MALTomas) are rare with no phase III trials to guide treatment. Typical management has been primary radiation therapy. This retrospective series aims to report the experience of a single institution and add to the current literature. Methods: Using our electronic medical record systems and available paper charts, we identified patients with MALTomas of the lacrimal gland or sac, conjunctiva, and posterior orbital structures. Records were reviewed to determine pathology, staging, treatment information, local and distant control, salvage treatments, and late toxicity. Results: Sixteen patients with ocular adnexal MALTomas had local radiation between 1992 and 2011 for primary or recurrent disease. 50% had lymphoma in the conjunctiva, 25% in the lacrimal sac/gland, and 25% in the posterior orbit. 75% had stage IAE disease, 6% had stage IIAE, and 19% had a positive bone marrow biopsy. One patient received chemotherapy as part of his initial therapy. The median radiation dose was 30 Gy (25.5-36 Gy) delivered with electrons (31%) or photons (69%). After a median follow-up of 34.78 months, two patients had residual/progressive disease, two had contralateral recurrence, and 1 had a distant failure, for local control of 87.5% and overall disease control of 68.75%. Recurrence/progression occurred at a median of 35.45 months. Two patients with residual/progressive disease and one with a contralateral recurrence were followed, successfully salvaged, and are NED. Fourteen patients are still alive and there were no disease-related/toxicity deaths. Seven patients developed cataracts in the treated eye, 2 had radiation retinopathy, 2 had permanent dry eye syndrome, and 1 had severe keratopathy requiring enucleation. Six patients (3.75%) had worsening visual acuity of unclear etiology. Conclusions: Primary radiation therapy for ocular adnexal MALTomas with a median dose of 30 Gy led to excellent local control. Those patients who did recur were successfully salvaged. Radiation was generally well-tolerated with expected cataractogenesis given the dose required to achieve local control with only one patient developing severe keratopathy after receiving the highest dose in this series.

Purpose. To evaluate the efficacy of laser thermotherapy (TT) and cryotherapy (CT) in the treatment of retinoblastoma of peripheral localization in standardized groups using comparative analysis. Material and methods. Comparative analysis of laser TT and CT was performed in two independent groups, which were standardized according to the main clinical characteristics: patients’ age at the time of treatment (p = 0.13), gender (p = 0.27), tumor height (p = 0.18) and largest basal diameter (p = 0.71), tumor stage (p = 0.31), previous chemotherapy type (p = 0.15) and the follow-up (p = 0.11). After standardization, the laser TT group consisted of 59 patients (61 eyes, 191 tumors); the CT group consisted of 57 patients (61 eyes, 87 tumors). Results. A comparative analysis of local tumor control rate in the groups of laser TT and CT showed statistically significant difference (p < 0.0001), calculated by chi-squared test: in laser TT group local tumor control was achieved in 88% of cases (n = 168), tumor progression/recurrence was observed in 11.5% cases (n = 23). In the CT group complete local control was achieved in 52% of cases (n = 45), incomplete regression with additional treatment was detected in 23% of cases (n = 20). Tumor progression/recurrence was observed in 25% of cases (n = 22) after CT. The incidence of complications also significantly differed depending on the method of local treatment (p = 0.012), calculated according to the Fisher’s exact test. There was no significant difference in the eye retention rate: 97% — in the TT group and 90% — in the CT group (p = 0.27), calculated according to the Fisher’s exact test. Conclusion. Thermotherapy is a highly effective approach in the treatment of retinoblastoma of peripheral localization and demonstrates higher local tumor control rate compared to CT (88 and 75%, respectively), lower complications rate (1.5 and 15%) and comparative eye retention rate (97 and 90%).

The management of patients with high-risk features after radical prostatectomy (RP) is controversial. Level 1 evidence demonstrates that adjuvant radiation therapy (RT) improves survival compared to no treatment; however, it may overtreat up to 30% of patients, as randomized clinical trials (RCTs) using salvage RT on observation arms failed to reveal a survival advantage of adjuvant RT. We, therefore, sought to determine the current view of adjuvant vs. salvage RT among North American genitourinary (GU) radiation oncology experts. A survey was distributed to 88 practicing North American GU physicians serving on decision-making committees of cooperative group research organizations. Questions pertained to opinions regarding adjuvant vs. salvage RT for this patient population. Treatment recommendations were correlated with practice patterns using Fisher's exact test. Forty-two of 88 radiation oncologists completed the survey; 23 (54.8%) recommended adjuvant RT and 19 (45.2%) recommended salvage RT. Recommendation of active surveillance for Gleason 3+4 disease was a significant predictor of salvage RT recommendation (p=0.034), and monthly patient volume approached significance for recommendation of adjuvant over salvage RT; those seeing <15 patients/month trended towards recommending adjuvant over salvage RT (p=0.062). No other demographic factors approached significance. There is dramatic polarization among North American GU experts regarding optimal management of patients with high-risk features after RP. Ongoing RCTs will determine whether adjuvant RT improves survival over salvage RT. Until then, the almost 50/50 division seen from this analysis should encourage practicing clinicians to discuss the ambiguity with their patients.

Although positron-emission tomography (PET) plays an integral role in cervix cancer diagnosis, there are limited data on PET-based image-guided brachytherapy (IGBT). We aimed to report the long-term outcomes of PET-based IGBT. We reviewed 151 patients treated with definitive radiotherapy (RT), including PET-based IGBT between 2009 and 2018. After median 45Gy of external beam RT with the four-field technique, a median 24Gy of high-dose-rate iridium-192 IGBT was delivered in six fractions with Fletcher-Suit tandem and ovoids. All patients underwent 18F-fluorodeoxyglucose-PET/computed tomography planning with a brachytherapy applicator. Multivariable analysis of local control (LC) was performed using Cox regression analysis. The median high-risk clinical target volume (HRCTV) and HRCTV D90% were 51.8 (interquartile range [IQR] 35.9-79.4) cm3 and 77.7 (IQR 74.7-81.2) Gy, respectively. With a median follow-up of 57 (IQR 24.3-81.4) months, the 5-year LC rate was 89.2%. HRCTV ≥72 cm3 was associated with inferior LC (hazard ratio, 3.72, p=.017) after multivariable analysis: the 5-year LC rates were 94.0% and 77.9% for HRCTVs ≥72 and<72 cm3 , respectively (p=.002). The impact of HRCTV D90% ≥70Gy on LC was significant in patients with an HRCTV ≥72 cm3 compared to that in those with HRCTV<72 cm3 . Patients with adeno/adenosquamous carcinoma demonstrated inferior LC in both groups. There were 13 (8.6%) and 11 (7.3%) patients with acute and late severe toxicities after RT. PET-based IGBT leads to favorable LC, and HRCTV ≥72 cm3 requires further dose escalation to improve outcomes.

MP14-11 WHEN IS THE OPTIMAL TIMING FOR SALVAGE RADIATION THERAPY IN PATIENTS WITH INCREASING PSA AFTER RADICAL PROSTATECTOMY? A PATIENT RISK STRATIFICATION MODEL BASED ON PROSTATE CANCER AGGRESSIVENESS

89 Background: Stereotactic body radiosurgery (SBRT) is a recent innovation in the treatment of prostate cancer that has begun to disseminate into national practice. Comparative studies have yet to be performed and little is known about the cost to Medicare or difference in toxicity between SBRT and intensity modulated radiation therapy (IMRT). Methods: We performed a retrospective study using a national sample of all Medicare beneficiaries age 66 or older who received SBRT or IMRT as primary treatment for prostate cancer during 2008 through 2011. Each SBRT patient was matched to two IMRT patients with similar follow-up (6, 12, or 24 months) and clinical and demographic characteristics. Cost of treatment was calculated for matched patients with six months of follow-up. We assessed toxicity by searching Medicare claims for procedure or diagnosis codes indicative of treatment related toxicity. We used a random effects model to compare the likelihood of genitourinary (GU), gastrointestinal (GI), and other toxicity from 0 to 6, 0 to 12, and 0 to 24 months after the initiation of SBRT or IMRT treatment. Results: The study sample consisted of 1,335 SBRT patients matched to 2,670 IMRT patients. The mean cost of SBRT was $11,668 compared to $15,838 for IMRT. At all follow-up points, SBRT patients were significantly more likely to experience GU toxicity. In the first six months after treatment initiation, 15.6% of SBRT versus 12.6% of IMRT patients had claim indicative of a GU complication (p=.009). In the first 12 months, 27.1% of SBRT versus 23.2% of IMRT had a GU complication (p=.014). Finally, from 0-24 months, 43.9% of SBRT versus 36.3% of IMRT had a GU complication (p=.001). The higher rate of GU toxicity after SBRT was largely due to an increase in urethral strictures and bladder outlet obstructions and urinary incontinence or obstruction. Conclusions: In this retrospective observational study, while SBRT was associated with lower costs, there was a greater rate of urinary obstructive toxicity for patients undergoing SBRT compared to IMRT at all time points studied. Whether this increased rate of complication is offset by a higher cure rate or lower cost should be the subject of further study.

To assess gastrointestinal (GI) and genitourinary (GU) toxicity in patients treated with salvage radiotherapy (SRT) at doses of 70.2 Gy after radical retropubic prostatectomy (RRP). Medical records were reviewed retrospectively to identify patients treated with SRT after RRP between January 1999 and December 2005. Of the 62 patients identified, 30 were included for analysis. GI and GU toxicity was assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events and the American Urological Association Symptom Index (AUASI), respectively. The median AUASI score of the 17 patients with scores before SRT was 4, of the 24 with scores after SRT was 6, and of the 15 with scores before and after SRT the median increase was 3. Of the 29 patients with GI toxicity data, nine (31%) had diarrhoea after SRT (three after <70.2 Gy and six after 70.2 Gy). In all cases, the diarrhoea was mild (grade 1). Of all patients, 12 (41%) had proctitis after SRT (four after <70.2 Gy and eight after 70.2 Gy); the proctitis was grade 1 in four and grade 2 in eight, with no cases of grade 3 proctitis. There was no statistically significant difference in the median change in AUASI scores and GI toxicity incidence between patients receiving <70.2 or 70.2 Gy of SRT. High-dose SRT (70.2 Gy) is generally well tolerated with acceptable low-grade GI toxicity and minimal changes in AUASI scores.

The safety and efficacy of dose-escalated radiotherapy with intensity-modulated radiotherapy (IMRT) and image-guided radiotherapy (IGRT) remain unclear in salvage radiotherapy (SRT) after radical prostatectomy. We examined the impact of these advanced radiotherapy techniques and dose intensification on the toxicity of SRT. This multi-institutional retrospective study included 421 patients who underwent SRT at the median dose of 66 Gy in 2-Gy fractions. IMRT and IGRT were used for 225 (53%) and 321 (76%) patients, respectively. At the median follow-up of 50 months, the cumulative incidence of late grade 2 or higher gastrointestinal (GI) and genitourinary (GU) toxicities was 4.8% and 24%, respectively. Multivariate analysis revealed that the non-use of either IMRT or IGRT, or both (hazard ratio [HR] 3.1, 95% confidence interval [CI] 1.8–5.4, p < 0.001) and use of whole-pelvic radiotherapy (HR 7.6, CI 1.0–56, p = 0.048) were associated with late GI toxicity, whereas a higher dose ≥68 Gy was the only factor associated with GU toxicities (HR 3.1, CI 1.3–7.4, p = 0.012). This study suggested that the incidence of GI toxicities can be reduced by IMRT and IGRT in SRT, whereas dose intensification may increase GU toxicity even with these advanced techniques.

We sought to investigate whether enzalutamide (ENZA), without concurrent androgen deprivation therapy, increases freedom from prostate-specific antigen (PSA) progression (FFPP) when combined with salvage radiation therapy (SRT) in men with recurrent prostate cancer after radical prostatectomy (RP). Men with biochemically recurrent prostate cancer after RP were enrolled into a randomized, double-blind, phase II, placebo-controlled, multicenter study of SRT plus ENZA or placebo (ClinicalTrials.gov identifier: NCT02203695). Random assignment (1:1) was stratified by center, surgical margin status (R0 v R1), PSA before salvage treatment (PSA ≥ 0.5 v < 0.5 ng/mL), and pathologic Gleason sum (7 v 8-10). Patients were assigned to receive either ENZA 160 mg once daily or matching placebo for 6 months. After 2 months of study drug therapy, external-beam radiation (66.6-70.2 Gy) was administered to the prostate bed (no pelvic nodes). The primary end point was FFPP in the intention-to-treat population. Secondary end points were time to local recurrence within the radiation field, metastasis-free survival, and safety as determined by frequency and severity of adverse events. Eighty-six (86) patients were randomly assigned, with a median follow-up of 34 (range, 0-52) months. Trial arms were well balanced. The median pre-SRT PSA was 0.3 (range, 0.06-4.6) ng/mL, 56 of 86 patients (65%) had extraprostatic disease (pT3), 39 of 86 (45%) had a Gleason sum of 8-10, and 43 of 86 (50%) had positive surgical margins (R1). FFPP was significantly improved with ENZA versus placebo (hazard ratio [HR], 0.42; 95% CI, 0.19 to 0.92; P = .031), and 2-year FFPP was 84% versus 66%, respectively. Subgroup analyses demonstrated differential benefit of ENZA in men with pT3 (HR, 0.22; 95% CI, 0.07 to 0.69) versus pT2 disease (HR, 1.54; 95% CI, 0.43 to 5.47; Pinteraction = .019) and R1 (HR, 0.14; 95% CI, 0.03 to 0.64) versus R0 disease (HR, 1.00; 95% CI, 0.36 to 2.76; Pinteraction = .023). There were insufficient secondary end point events for analysis. The most common adverse events were grade 1-2 fatigue (65% ENZA v 53% placebo) and urinary frequency (40% ENZA v 49% placebo). SRT plus ENZA monotherapy for 6 months in men with PSA-recurrent high-risk prostate cancer after RP is safe and delays PSA progression relative to SRT alone. The impact of ENZA on distant metastasis or survival is unknown at this time.