Salvage Reirradiation Research Articles

Salvage Reirradiation with Proton Beam Therapy for Locoregionally Recurrent Non-Small Cell Lung Cancer.

This retrospective study evaluates outcomes of 66 patients who underwent reirradiation (re-RT) with proton beam therapy (PBT) for recurrent non-small cell lung cancer. Toxicity was scored via the CTCAE v5.0, and outcomes estimated using the Kaplan-Meier method, with associations evaluated via Cox proportional hazards and logistic regression analyses. Patients were treated to a median re-RT prescription of 66 Gy/33 fxs (BED10 = 79 Gy; IQR: 71-84 Gy) at an interval of 1.4 years from prior RT. Half (50%) received concurrent chemotherapy. At 14 months follow-up, the median OS and PFS were 5 months (95%CI: 13-17) and 12.5 months (95%CI: 10-15), respectively. On multivariable analysis, a higher RT dose (BED10 > 70 Gy) [HR0.37; 95%CI: 0.20-0.68, p = 0.001] and concurrent chemotherapy (HR0.48; 95%CI: 0.28-0.81, p = 0.007) were associated with improved PFS, while treatment site overlap was adversely associated (HR1.78; 95%CI: 1.05-3.02, p = 0.031). The median PFS for definitive RT with concurrent chemotherapy (n = 28), definitive RT alone (BED10 > 70 Gy) [n = 22], and lower prescription RT (BED10 < 70 Gy) [n = 16] was 15.5 months (95%CI: 7.3-23.7), 14.1 months (95%CI: 10.9-17.3), and 3.3 months (95%CI: 0-12.3), respectively (log-rank, p = 0.006), with corresponding 2-year estimates of 37% (±9), 18% (±8), and 12.5% (±8), respectively. The incidence of Grade 3+ toxicity was 10.5% (6% pulmonary; 3% esophageal; and 1.5% skin), including one Grade 4 bronchopulmonary hemorrhage but no Grade 5 events. Cases with central site overlap had higher composite Dmax to the esophagus (median 87 Gy [IQR:77-90]), great vessels (median 120 Gy [IQR:110-138]), and proximal bronchial tree (median 120 Gy [IQR:110-138]) as compared to other cases (p ≤ 0.001 for all). However, no significant associations were identified with Grade 3+ events. Thoracic re-RT with PBT is an option for recurrent NSCLC with acceptable outcomes and toxicity for select patients. When feasible, higher prescription doses (BED10 > 70 Gy) should be delivered for definitive intent, and concurrent chemotherapy may benefit individual cases.

Salvage reirradiation for recurrent glioblastoma: a retrospective case series analysis.

To assess the clinical outcome of patients with recurrent glioblastoma treated with salvage reirradiation. Between 2005 and 2022, data from adult patients with glioblastoma treated with surgery and radio-chemotherapy Stupp regimen who developed a local in-field relapse and received stereotactic radiotherapy (SRT) were retrospectively reviewed. The study population included 44 patients with recurrent glioblastoma (median of 9.5 months after the first radiotherapy). Reirradiation alone was given to 47.7% of patients. The median maximum diameter of the recurrence was 13.5 mm. The most common SRT regimen (52.3%) was 35 Gy in 10 fractions. Acute toxicity was mild, with transient worsening of previous neurological symptoms in only 15% of patients. After a median follow-up of 15 months, 40% presented radiological response, but a remarkable number of early distant progressions were recorded (32.5%). The median time to progression was 4.8 months, being the dose, the scheme, the size of the recurrence or the strategy (exclusive RT vs. combined) unrelated factors. The median overall survival (OS) was 14.9 months. Karnofsky index < 70 and the size of the recurrence (maximum diameter < 25 mm) were significant factors associated with OS. Radiological changes after reirradiation were commonly seen (> 50% of patients) hindering the response assessment. Reirradiation is a feasible and safe therapeutic option to treat localized glioblastoma recurrences, able to control the disease for a few months in selected patients, especially those with good functional status and small lesions. Hypofractionated schemes provided a suitable toxicity profile. Radiological changes were common.

Systematic review and recommendations for re-irradiation for intraprostatic radiorecurrent prostate cancer after definitive radiation therapy.

Intraprostatic recurrence (IRR) of prostate cancer after radiation therapy is increasingly identified. Our objective was to review the literature to determine the optimal workup for identifying IRR, the management options, and practical considerations for the delivery of re-irradiation as salvage local therapy. We performed a systematic review of available publications and ongoing studies on the topics of IRR, with a focus on salvage re-irradiation. Work up of biochemically recurrent prostate cancer includes PSMA PET/CT and multiparametric MRI, followed by biopsy to confirm IRR. Management options include continued surveillance, palliative hormonal therapy, and salvage local therapy. Salvage local therapy can be delivered using re-irradiation with low dose rate brachytherapy, high dose rate (HDR) brachytherapy, and stereotactic body radiotherapy (SBRT), as well as non-radiation modalities, such as cryotherapy, high-intensity focused ultrasound, irreversible electroporation and radical prostatectomy. Data demonstrate that HDR brachytherapy and SBRT have similar efficacy compared to the other salvage local therapy modalities, while having more favorable side effect profiles. Recommendations for radiation therapy planning and delivery using HDR and SBRT based on the available literature are discussed. Salvage re-irradiation is safe and effective and should be considered in patients with IRR.

Local salvage therapies in patients with radio-recurrent prostate cancer following external beam radiotherapy: a systematic review and meta-analysis.

To date, radio-recurrent prostate cancer (PCa) ranks as the fourth most common urological malignancy when considering the number of men with localized PCa who undergo radiation treatment and subsequently experience a biochemical recurrence. This systematic review aimed to summarize available evidence about the outcomes of local salvage strategies in patients with local PCa recurrence following primary external-beam radiation therapy (EBRT). We conducted a comprehensive bibliographic search on MEDLINE, Scopus, and Web of Science Core Collection databases in October 2023 to identify studies published in the last 20 years evaluating outcomes of local salvage procedures in patients with locally radio-recurrent PCa following EBRT. The meta-analysis was performed using ProMeta 3 software when two or more studies reported the same outcome. The effect size (ES) was estimated using rates reported with its 95% confidence interval (CI). Overall, 28 studies (6 prospective and 22 retrospective) including 1544 patients were included in the review. Two-year recurrence-free survival (RFS) was 84.0% (95% CI: 67.0-93.0%), 69.0% (95% CI: 42.0-87.0%), 58.0% (95% CI: 43.0-71.0%), and 45% (95% CI: 38.0-52.0%), for patients undergoing brachytherapy (BT), EBRT, Cryotherapy and High-Intensity Focused Ultrasound (HIFU), respectively. After salvage prostatectomy, RFS ranged from 75% to 78.5% at a median follow-up ranging from 18 to 35 months. Estimates for severe gastrointestinal toxicity were 2%, 3%, 3%, 4%, and 11% following cryotherapy, BT, HIFU, EBRT, and salvage radical prostatectomy, respectively. In patients who underwent EBRT as primary treatment, prostate salvage re-irradiation through BT or EBRT represents the modality providing the best balance between efficacy and safety. Unfortunately, due to the low level of evidence, strong recommendations regarding the choice of any of these techniques cannot be made.

Pharyngeal Constrictor-Sparing Salvage Stereotactic Body Radiation Therapy With Tongue-Out for In-Field Recurrence After Definitive Radiation Therapy for Head and Neck Cancer: Guide to Tongue-Out Radiation Therapy

This report details a pharyngeal constrictor muscle (PCM)–sparing stereotactic body radiation therapy (SBRT) using our institutional technique of “tongue-out” radiation therapy (TORT) for treating a local recurrent cancer in the uvula (GTVuvula) in a patient with history of a definitive chemotherapy with radiation therapy (70 Gy with weekly cisplatin) for a locally advanced laryngeal cancer 4 years ago. TORT includes optimizing the patients’ reproducible tongue-out position using readily available medicine cup (30 cc) followed by sculping the thermoplastic mask with tongue-out, and real-time visual monitoring of the tongue position during the computed tomography simulation scan, cone beam computed tomography acquisition, and treatment. Between arcs during volumetric modulated arc therapy, time for tongue relaxation and saliva swallowing can be given to the patient. Without TORT, the patient's GTVuvula abutted the medial aspect of superior PCM (medial-sPCM) and a substantial volume of the previously irradiated superior PCM (sPCM) would have received high radiation dose from this salvage SBRT (32.5 Gy in 5 fractions). Comparing without TORT, the shortest distance between medial-sPCM-to-GTVuvula was increased by 13 mm with TORT, which reduced radiation dose to sPCM in the salvage SBRT plan. The mean dose to sPCM was decreased from 20.5 Gy without TORT to 12.7 Gy with TORT. With TORT, minimal sPCM volumes fell within higher isodose line: volume receiving ≥ 60% prescription dose (V60%Rx), V80%Rx, and V100%Rx to sPCM was, 4.8 versus 0.7 cc (without vs with TORT, respectively), 2.9 versus 0.19 cc, and 1.6 versus 0.04 cc, respectively. Maximum dose (Dmax) to medial-sPCM was 34.6 Gy without TORT versus 22.7 Gy with TORT. These high doses to the sPCM and intrafractional swallowing-related geographic misses of GTVuvula were avoided through the application of TORT in this salvage reirradiation setting. The patient successfully finished salvage SBRT with TORT resulting in no dysphagia or mucositis and maintained complete response at 12 months after treatment.

Salvage Reirradiation for Locally Recurrent Prostate Cancer: Results From a Prospective Study With 7.2 Years of Follow-Up.

There are no well-established re-treatment options for local recurrence after primary curative radiation therapy for prostate cancer (PCa), as prospective studies with long-term follow-up are lacking. Here, we present results from a prospective study on focal salvage reirradiation with external-beam radiation therapy with a median follow-up of 7.2 years. From 2013 to 2017, 38 patients with biopsy-proven locally recurrent PCa >2 years after previous treatment and absence of grade 2-3 toxicity from the first course of radiation were included. The treatment was 35 Gy in five fractions to the MRI-based target volume and 6 months of androgen-deprivation therapy starting 3 months before radiation. The Phoenix criteria defined biochemical recurrence-free survival (bRFS), and toxicity was scored according to Radiation Therapy Oncology Group criteria. Median age was 70 years, and median time from primary radiation to prostate-specific antigen (PSA) recurrence was 83 months. The actuarial 2-year and 5-year bRFS were 81% (95% CI, 69 to 94) and 58% (95% CI, 49 to 74), respectively. The actuarial 5-year local recurrence-free survival was 93% (95% CI, 82 to 100), metastasis-free survival was 82% (95% CI, 69 to 95), and overall survival was 87% (95% CI, 76 to 98). Two patients (5%) had durable grade 3 genitourinary toxicity, one combined with GI grade 3 toxicity. A PSA doubling time ≤6 months at salvage, a Gleason score >7, and a PSA nadir ≥0.1 ng/mL predicted a worse outcome. Reirradiation with EBRT for locally recurrent PCa after primary curative radiation therapy is clinically feasible and demonstrated a favorable outcome with acceptable toxicity in this prospective study with long-term follow-up.

40 Gray in 5 Fractions for Salvage Reirradiation of Spine Lesions Previously Treated With Stereotactic Body Radiotherapy.

A retrospective single-center analysis of the safety and efficacy of reirradiation to 40 Gy in 5 fractions (reSBRT) in patients previously treated with stereotactic body radiotherapy to the spine was performed. We identified 102 consecutive patients treated with reSBRT for 105 lesions between 3/2013 and 8/2021. Sixty-three patients (61.8%) were treated to the same vertebral level, and 39 (38.2%) to overlapping immediately adjacent levels. Local control was defined as the absence of progression within the treated target volume. The probability of local progression was estimated using a cumulative incidence curve. Death without local progression was considered a competing risk. Most patients had extensive metastatic disease (54.9%) and were treated to the thoracic spine (53.8%). The most common regimen in the first course of stereotactic body radiotherapy was 27 Gy in 3 fractions, and the median time to reSBRT was 16.4 months. At the time of simulation, 44% of lesions had advanced epidural disease. Accordingly, 80% had myelogram simulations. Both the vertebral body and posterior elements were treated in 86% of lesions. At a median follow-up time of 13.2 months, local failure occurred in 10 lesions (9.5%). The 6- and 12-month cumulative incidences of local failure were 4.8% and 6%, respectively. Seven patients developed radiation-related neuropathy, and 1 patient developed myelopathy. The vertebral compression fracture rate was 16.7%. In patients with extensive disease involvement, reSBRT of spine metastases with 40 Gy in 5 fractions seems to be safe and effective. Prospective trials are needed to determine the optimal dose and fractionation in this clinical scenario.

Post- versus intra-operative implant for breast cancer interstitial brachytherapy: How to choose?

Breast brachytherapy (BB) represents an important radiation therapy modality in modern breast cancer treatments. Currently, BB is mainly used for accelerated partial breast irradiation (APBI), local boost after whole breast radiation therapy (WBRT), and as salvage re-irradiation after second lumpectomy (APBrl). Two multi-catheter interstitial brachytherapy (MIB) techniques can be offered: intra-operative (IOB) and post-operative (POB) brachytherapy. The aim of this article was to summarize current available data on these two different brachytherapy approaches for breast cancer. A literature search was performed, and different experiences published by BB expert teams were analyzed and compared. These two different brachytherapy approaches for breast cancer have also been presented and discussed during meetings of the GEC-ESTRO BCWG. In addition, expert recommendations were defined. A comprehensive description and practical comparison of both the techniques, i.e., IOB and POB, considering the latest available published data were presented. Different technical, logistic, and clinical aspects of both the methods were thoroughly examined and analyzed. This detailed comparison of the two breast brachytherapy techniques was supported by scientific data from extensive experience of experts, facilitating an objective analysis that, to our knowledge, has not been previously published. Based on the comprehensive analysis of both the brachytherapy techniques available, this article serves as a valuable resource to guide breast teams in selecting the optimal BB technique (POB or IOB), considering hospital environment, multi-disciplinary collaboration, and patient logistics.

Stereotactic body radiotherapy (SBRT) re-irradiation for local failures following radical prostatectomy and post-operative radiotherapy.

Local recurrences after radical prostatectomy (RP) and postoperative radiotherapy (RT) are challenging for salvage treatment. Retrospective analysis of own experiences with salvage re-irradiation was performed. The study included all consecutive patients treated with salvage stereotactic body radiotherapy (sSBRT) for prostate bed recurrence following RP and postoperative RT at asingle tertiary center between 2014 and 2021. Treatment toxicity defined as the occurrence of CTCAE grade ≥ 2 genito-urinary (GU) or gastro-intestinal (GI) adverse events (AEs) was assessed. APSA response, biochemical control (BC) and overall survival (OS) were also evaluated. The study group included 32patients with amedian age of 68years and amedian follow-up of 41months, treated with CyberKnife (53%) or Linac (47%) sSBRT. Total dose of 33.75-36.25 Gy in five fractions (72%) was applied in the majority of them. Approximately 19% patients reported grade ≥ 2 GU AEs both at baseline and at three months, and grade ≥ 2 GI toxicity increased from 0% at baseline to 6% at three months after sSBRT. There was some clinically relevant increase in late toxicity with 31% patients reporting late ≥ 2 GU, and 12.5% late ≥ 2 GI AEs. Two grade3 AEs were recorded: recto-urinary fistulas. The majority of patients showed aPSA response (91% at one year post-sSBRT). The 3‑year BC was 40% and 3‑year OS was 87%. Manageable toxicity profile and satisfactory biochemical response suggest that SBRT in patients with local recurrence following RP and postoperative RT might be asalvage option for selected patients.

Salvage re-irradiation in non-melanoma skin cancers: A multicenter analysis

Background and purposeWe conducted a multicentre real-world study to assess the outcomes of radical salvage re-irradiation for non-melanoma skin cancer (nMSC) recurrences following definitive or postoperative radiotherapy. Materials and methodsData on patients treated between 2006 and 2022 with re-irradiation for nMSCs were retrospectively collected from five high-volume brachytherapy centers. The primary endpoint was local control (LC). Secondary endpoints included overall survival, progression-free survival, and adverse events (AEs). The Kaplan-Meier estimator and Cox Proportional-Hazards Model were utilised in the analysis. ResultsA total of 58 patients with a median age of 78.4 years with recurrences of previously irradiated nMSC in the head and neck region were included in the analysis. The majority had cutaneous basal cell carcinoma (BCC; 91.4%), and were irradiated with high-dose-rate brachytherapy (HDR-BT; 91.4%). The most common locations included the nasal region (36.2%) and external ear (18.9%). The 1-year LC was 73.1% and decreased to 41.7% at three years. The size of the re-irradiated lesion was the single independent prognostic factor in Cox analysis (per mm; HR 1.07; 95% CI 1.04–1.11; p < 0.001). Grade 3 or worse AEs were reported in 7 cases (12.1%). ConclusionRe-irradiation for nMSCs, predominantly administered with brachytherapy for radiorecurrent BCC, is associated with high recurrence rates, and the risk of failure significantly increases with the size of the treated lesion. Re-irradiation could be an option for selected elderly patients with small, localised, inoperable recurrences after RT to achieve local control or defer systemic treatment; however, prospective trials are necessary to confirm its safety and efficacy.

Cesium-131 Low-Dose Rate Interstitial Brachytherapy as a Salvage Re-Irradiation Technique in Treating Cervical and Uterine Cancer Pelvic Recurrence with Prior History of Pelvic Radiation

Pelvic recurrence among cervical and uterine cancer patients with prior history of pelvic radiation is a poor prognostic factor and remains challenging. The standard of care is pelvic exenteration, which is a highly morbid surgical procedure. The purpose of this study is to report local control rate and toxicity profile of Cesium-131 low-dose rate interstitial brachytherapy (LDR) as a salvage re-irradiation technique in managing pelvic relapse. We reviewed procedures and outcomes from patients with previously irradiated uterine corpus or cervix neoplasms, who subsequently relapsed and then underwent cesium-131 LDR implants between January 2016 and December 2022. Patient demographics, treatment planning variables, and disease response were reviewed. Acute toxicities, late toxicities, and local control rate were compiled for this study. A total of 12 eligible patients (6 cervical and 6 uterine cancer) with 16 cesium-131 LDR implants were included in this study. The majority (75%) of pelvic relapses occurred at the exocervix (cervix-intact) or vaginal cuff (post-hysterectomy). Median time from disease relapse to cesium implant was 32 days. The average area of implementation was 9 cm2 and average number of seeds implanted was 16. The mean prescription dose was 50 Gy. Six patients also received high-dose rate vaginal intracavitary brachytherapy in addition to cesium-131 LDR. Median follow up was 12 months. 81% of cesium implants achieved complete response at first post-treatment follow-up, while the remaining 19% demonstrated partial response. The 6-months local control rate was 79%. After cesium implant, 25% patients had local recurrence and 33% with distal metastasis. The most reported acute toxicities included vaginal mucositis (63%), dysuria (50%) and pain (19%). All patients had various degrees of vaginal stenosis and strictures long-term. Only 1 (8%) out of 12 patients, with 4 repeated cesium-131 LDR implants, developed a rectovaginal fistula and chronic pain. Cesium-131 LDR interstitial brachytherapy is a safe and feasible salvage re-irradiation technique in treating pelvic relapse among uterine corpus or cervix cancer patients with prior history of pelvic radiation. Local control rate at 6-months was acceptable with minimum toxicity. Long-term follow up is warranted to validate the efficacy of cesium-131 LDR. We conclude that cesium-131 LDR interstitial brachytherapy is a promising alternative to pelvic exenteration in selective patient population. Future prospective study is warranted.

Re-irradiation for recurrent head and neck cancer: Freedom from cancer recurrence rate.

e18077 Background: Salvage re-irradiation (rRT) for patients with locoregionally recurrent head and neck cancer (rHNC) remains challenging. Methods: A retrospective analysis was performed on patients who received rRT between 2011 and 2018. The co-primary endpoint of the study was 2-year freedom from cancer recurrence rate (FCRR) and overall survival (OS), and secondary endpoints were 2-year disease free survival (DFS), local failure (LF), regional failure (RF), distant metastases (DM), and RTOG grade 3≥ late toxicities. Results: A total of 49 cases [nasopharygeal (n = 12); laryngeal (n = 12); oral cavity (n = 11); salivary gland (n = 9); and skin (n = 5)] were identified, adjuvant or definitive rRT were delivered to 22 and 27 patients, respectively. Various rRT fractionation schedules were used and 35/49 (71%) of patients received concurrent chemotherapy. The median follow-up after rRT was 30 months. The 2-year OS, DFS, LF, RF, and DM and FCRR were 64%, 51%, 28%, 32%, 9%, and 39% respectively. MVA showed that poor performance status (PS: 1-2 vs 0) and age &gt; 52 years were predictive of worse OS. While, poor PS (1-2 vs 0) and total dose of rRT &lt; 60Gy were predictive of worse DFS. Late RTOG toxicity of grade 3≥ was reported in 9(18.3%) patients. Conclusions: FCRR at 2 years after salvage rRT for rHNC was higher than other traditional endpoints and could be an important new endpoint to be included in the rRT studies. rRT for rHNC at our cohort was successful; with a manageable level of late sever toxicity.

Re-Irradiation for Recurrent Head and Neck Cancer: Freedom from Cancer Recurrence Rate.

Salvage re-irradiation (rRT) for patients with locoregionally recurrent head and neck cancer (rHNC) remains challenging. A retrospective analysis was performed on 49 patients who received rRT between 2011 and 2018. The co-primary endpoint of the study was 2-year freedom from cancer recurrence rate (FCRR) and overall survival (OS), and secondary endpoints were 2-year disease-free survival (DFS), local failure (LF), regional failure (RF), distant metastases (DM), and RTOG grade 3 ≥ late toxicities. Adjuvant and definitive rRT were delivered to 22 and 27 patients, respectively. A total of 91% of patients were managed with conventional re-RT and 71% of patients received concurrent chemotherapy. The median follow-up after rRT was 30 months. The 2-year FCRR, OS, DFS, LF, RF, and DM were 64%, 51%, 28%, 32%, 9%, and 39% respectively. MVA showed that poor performance status (PS: 1-2 vs. 0) and age > 52 years were predictive of worse OS. In comparison, poor PS (1-2 vs. 0) and total dose of rRT < 60 Gy were predictive of worse DFS. Late RTOG toxicity of grade 3 ≥ was reported in nine (18.3%) patients. FCRR at 2 years after salvage rRT for rHNC was higher than other traditional endpoints and could be an important endpoint to be included in future rRT studies. rRT for rHNC at our cohort was relatively successful, with a manageable level of late severe toxicity. Replacing this approach in other developing countries is a viable option.

Long-Term Outcomes of Stereotactic Body Radiotherapy (SBRT) for Intraprostatic Relapse after Definitive Radiotherapy for Prostate Cancer: Patterns of Failure and Association between Volume of Irradiation and Late Toxicity.

The aim of this retrospective study was to assess the adverse effects and outcomes of salvage re-irradiation with stereotactic body radiotherapy (sSBRT) for local recurrence of prostate cancer (PCa) after definitive radiotherapy (RT). The study was focused on the adverse effects and prognostic factors for treatment toxicity, followed by an analysis of patterns of failure and survival. Patients treated with sSBRT between 2012 and 2020 at a tertiary institution were included. The exclusion criteria were a primary or salvage radical prostatectomy or a palliative sSBRT dose. Patients with oligorecurrence were eligible if all metastatic lesions were treated locally with curative intent. The Kaplan-Meier method was used to estimate time to grade ≥ 3 toxicity, local control (LC), freedom from distant metastases (FFDM), progression-free survival (PFS), biochemical control (BC) and overall survival (OS). The differences between groups (focal vs. whole-gland sSBRT) were compared using the log-rank test. The Cox proportional hazards model was used to assess prognostic factors for the listed endpoints. A total of 56 patients with a median age of 70.9 years and a median follow-up of 38.6 months were included in the analysis. The majority of them received local sSBRT only (45; 80.4%), while the rest were simultaneously treated for oligometastases (11; 19.6%). Overall, 18 (32.1%) patients experienced any grade ≥ 3 toxicity, including 1 (6.7%) patient who received focal sSBRT, and 17 (41.5%) patients treated with whole-gland sSBRT. The Planning Target Volume (per cc; HR 1.01; 95% CI 1-1.02; p = 0.025) and use of ADT (yes vs. no; HR 0.35; 95%CI 0.13-0.93; p = 0.035) were independent prognostic factors for the risk of grade ≥ 3 toxicity. The estimated rate of grade ≥ 3 adverse events was significantly higher (43.8% vs. 7.1% at 2 years; p = 0.006), and there was no improvement in the LC (92.9% vs. 85.3% at 2 years; p = 0.759) in patients treated with whole-gland sSBRT compared to focal sSBRT. The 2- and 5-year LC were 87.6% and 47.9%, respectively; the 2- and 5-year FFDM were 72.7% and 42.8%, respectively; and the 2- and 5-year PFS were 67.9% and 28.7%, respectively. The primary pattern of failure was distant metastasis. The sSBRT for local recurrence of PCa after definitive RT was associated with a high risk of severe grade ≥ 3 toxicity, which significantly increased with the volume and extent of re-irradiation.

Linac-based stereotactic salvage reirradiation for intraprostatic prostate cancer recurrence: toxicity and outcomes

BackgroundThe rates of local failure after curative radiotherapy for prostate cancer (PC) remain high despite more accurate locoregional treatments available, with one third of patients experiencing biochemical failure and clinical relapse occurring in 30–47% of cases. Today, androgen deprivation therapy (ADT) is the treatment of choice in this setting, but with not negligible toxicity and low effects on local disease. Therefore, the treatment of intraprostatic PC recurrence represents a challenge for radiation oncologists. Prostate reirradiation (Re-I) might be a therapeutic possibility. We present our series of patients treated with salvage stereotactic Re‑I for intraprostatic recurrence of PC after radical radiotherapy, with the aim of evaluating feasibility and safety of linac-based prostate Re‑I.Materials and methodsWe retrospectively evaluated toxicities and outcomes of patients who underwent salvage reirradiation using volumetric modulated arc therapy (VMAT) for intraprostatic PC recurrence. Inclusion criteria were age ≥ 18 years, histologically proven diagnosis of PC, salvage Re‑I for intraprostatic recurrence after primary radiotherapy for PC with curative intent, concurrent/adjuvant ADT with stereotactic body radiation therapy (SBRT) allowed, performance status ECOG 0–2, restaging choline/PSMA-PET/TC and prostate MRI after biochemical recurrence, and signed informed consent.ResultsFrom January 2019 to April 2022, 20 patients were recruited. Median follow-up was 26.7 months (range 7–50). After SBRT, no patients were lost at follow-up and all are still alive. One- and 2‑year progression free survival (PFS) was 100% and 81.5%, respectively, while 2‑year biochemical progression-free survival (bFFS) was 88.9%. Four patients (20%) experienced locoregional lymph node progression and were treated with a further course of SBRT. Prostate reirradiation allowed the ADT start to be postponed for 12–39 months. Re‑I was well tolerated by all patients and none discontinued the treatment. No cases of ≥ G3 genitourinary (GU) or gastrointestinal (GI) toxicity were reported. Seven (35%) and 2 (10%) patients experienced acute G1 and G2 GU toxicity, respectively. Late GU toxicity was recorded in 10 (50%) patients, including 8 (40%) G1 and 2 (10%) G2. ADT-related side effects were found in 7 patients (hot flashes and asthenia).ConclusionLinac-based SBRT is a safe technique for performing Re‑I for intraprostatic recurrence after primary curative radiotherapy for PC. Future prospective, randomized studies are desirable to better understand the effectiveness of reirradiation and the still open questions in this field.

Delta-radiomics Entropy Based on Tumor Heterogeneity Concept – Response Predictor to Irradiation for Unresectable/recurrent Glioblastoma

Although adjuvant radiotherapy in combination with Temozolomide administration has clearly demonstrated the benefit in improving the prognosis of patients with multiforme glioblastoma, radiotherapy as only treatment or in combination with systemic treatment is one of the best supportive in unresectable cases. For recurrent cases, the salvage radiotherapy option (re-irradiation) can be chosen in carefully selected cases so that the benefit is greater than the toxicities. Radiomics, a new subdomain of artificial intelligence (AI), relies on advanced analysis in high-resolution medical imaging to establish diagnostic, prognostic and predictive models for clinical medicine. The variation of the delta-radiomics parameters analyzed within a tumor volume may be via tumor heterogeneity indirectly correlated with the response to treatment. The aim of the study is to propose a delta-radiomic based on entropy algorithm to allow the non-invasive pre-therapeutic identification of patients with unresectable or recurrent multiform glioblastoma who will benefit from irradiation and/or salvage re-irradiation.

Salvage Re-Irradiation with Proton Beam Therapy for New or Locoregionally Recurrent Non-Small Cell Lung Cancer

<h3>Purpose/Objective(s)</h3> Outcomes have improved for Stage III non-small cell lung cancer (NSCLC) patients, but up to 25% can experience isolated locoregional recurrence after definitive chemo-RT. Salvage re-irradiation represents a high-risk but potentially definitive option for these cases, and advancements in particle therapy may enhance the feasibility of re-treatment. <h3>Materials/Methods</h3> This retrospective study evaluates 66 patients who underwent salvage re-irradiation with proton beam therapy at our cancer center for new or recurrent NSCLC within or adjacent to a prior definitive RT field. All patients underwent multidisciplinary evaluation and full restaging work-up prior to re-treatment. Toxicity was scored via CTCAE v5.0, and outcomes were estimated using Kaplan-Meier. Associations were analyzed via Cox proportional hazards and logistic regression. <h3>Results</h3> Patients received IMPT (32%) or passive scatter (68%) to a median re-RT dose of 60-CGE in 30-fractions for new (8%) or recurrent (92%) non-small cell lung cancer (NSCLC), at a median time of 2-years (range: 1-3) from prior thoracic RT (with 23% previously receiving ≥2 courses). More than half (55%) received chemotherapy with proton re-RT: 32 (48%) concurrently, 4 induction (pre-RT), and 1 both. At a follow-up of 13.5 months, the median OS and PFS were 15-months (95% CI 13-17) and 12-months (95% CI 9.5-15), respectively. Actuarial OS at 1-year and 2-years was 61% and 32%, corresponding to PFS of 54% and 24%. Age >70 was associated with greater mortality (HR 2.23, p=0.011), while concurrent chemotherapy was associated with improved PFS (HR 0.53, p=0.022). Altogether, 30 patients (45%) ultimately demonstrated progression, including isolated locoregional recurrence among 16 (24%), isolated distant progression among 8 (12%), and combined site as first presentation among 6 (9%). The incidence of any Grade 2+ toxicity was 26% (including 8 pulmonary and 13 esophageal) and associated with RT dose >60CGE (OR 3.78, p=0.025) and age >70 (OR 0.29, p=0.036). Grade 3 events among 4 patients (6%) included: bronchial stenosis with hemoptysis (following Dmax >140 Gy to PBT), esophageal strictures (occurring at Dmax 77-88 Gy), and pneumonitis (despite meeting standard constraints). There were no cardiac, neurologic, or vascular toxicities. No grade 4 or 5 events. <h3>Conclusion</h3> Reirradiation with proton beam therapy can be safe with minimal toxicity and promising outcomes (which may be further enhanced by concurrent chemotherapy). However, older patients may be at greater risk, and adverse events can still occur despite meeting literature-supported constraints.

Outcomes and Toxicity Following Three or More Definitive Courses of Thoracic Radiation Therapy

<h3>Purpose/Objective(s)</h3> Lung cancer patients are living longer but remain at risk for developing new or recurrent disease. Salvage re-irradiation can be considered for definitive management, but balancing efficacy with associated toxicity poses difficulty with retreatment. <h3>Materials/Methods</h3> This retrospective study evaluates patients who underwent three or more courses of definitive RT for thoracic malignancies at our cancer center from 2012 through 2021. All patients underwent multidisciplinary evaluation and restaging prior to retreatment. Toxicity was scored via CTCAE v5.0, and outcomes were estimated via Kaplan-Meier. <h3>Results</h3> Fifty-nine patients underwent a total of 190 definitive courses (13 having received 4 courses) for new or recurrent thoracic malignancies (88% non-small cell lung cancer). Of these courses, 141 (74%) entailed SBRT for localized lesions (most commonly to 50-Gy in 4-fractions), while the remaining 49 (26%) consisted of conventional fractionation (most often delivered with concurrent chemotherapy), with 22 patients (37%) receiving SBRT for every course. Median follow-up time was 7-years and 20-months from initial diagnosis and last RT course, respectively. All patients maintained excellent performance status (ECOG 0-2 or KPS 70-90) from first to last treatment. Median age at initial diagnosis and at last course of thoracic RT was 68.5 and 71 years, respectively, corresponding to median interval from initial RT to last RT course of 4 years. Twenty-eight patients (47%) had history of pulmonary disease, while 19 (32%) had history of prior lobectomy. Following last thoracic RT, median overall survival (OS) and progression-free survival (PFS) were still 2.4 years (95% CI: 1-4) and 12-months (95% CI 7-18), respectively. Actuarial OS at 1-year and 2-years was 73% and 54%, corresponding to PFS of 50% and 27%. However, 47 patients (80%) ultimately had evidence of progression, including distant metastases among 20 (43%), isolated locoregional recurrences in 19 (40%), and both as first progression for 8 (17%). Following last RT, the incidence of Grade 3 toxicity was only 5% (pulmonary and esophageal), with no Grade 4-5 events. There were no cardiac, neurological, or vascular toxicities directly attributable to RT. <h3>Conclusion</h3> Re-RT often remains a safe and effective local control modality (despite prior treatment) and should be considered as a potential option when planning multidisciplinary salvage therapy. For isolated failures, multiple courses of thoracic RT (notably SBRT) can be delivered sequentially with minimal toxicity.

40 Gray in 5 Fractions for Salvage Re-Irradiation of Spine Lesions Previously Treated with Stereotactic Body Radiotherapy

<h3>Purpose/Objective(s)</h3> This is a retrospective single-center analysis of the safety and efficacy of re-irradiation to 40 Gray (Gy) in 5 fractions in patients previously treated with stereotactic body radiotherapy (SBRT) to the spine. <h3>Materials/Methods</h3> We identified 62 consecutive patients with various solid malignancies treated between January 2016 and December 2021 to 40 Gy in 5 fractions regardless of dose and fractionation at the first course of SBRT. Patients were followed clinically and with routine imaging. Acute (≤3 months) and late (>3 months) toxicities were assessed according to CTCAE v5.0. Local control was defined as absence of progression within the treated target volume. Time to progression was calculated from date of completion of SBRT to the date of an imaging study indicating progression. The probability of local progression before death was estimated using a cumulative incidence curve, and death without local progression was considered a competing risk. <h3>Results</h3> Most patients had oligometastatic disease (53.2%) and treated to the thoracic spine (51.6%). The most common fractionation regimen in the first course of SBRT was 27 Gy in 3 fractions, and the median time to re-irradiation was 13.1 months (range, 2.4-86.9 months). Twenty-four patients (38.7%) had surgery before re-irradiation. At time of simulation, 49 patients (79%) had epidural disease, including 19, 13, 12 and 5 patients with epidural spinal cord compression (ESCC) scale 1a, 1b, 1c and 2, respectively. Accordingly, myelogram simulations were performed in 82.2% of patients. Both the vertebral body and posterior elements were treated in 93.5% of patients. All early toxicities were low grade, apart from one case of grade 3 fatigue, one case of grade 3 diarrhea and one case of grade 3 pneumonitis. Five patients experienced a pain flare (8.1%). Two thirds of patients who reported pain at baseline, achieved improvement (33%) or complete resolution of pain (33%). About 40% of patients had at least a partial response in magnetic resonance imaging (MRI). At a median follow up time of 11.9 months (range, 1.8- 39.6 months), six patients (9.7%) suffered local progression. The median time to progression was 4.1 months (range, 1.93-13.8 months). The estimated incidence rate of local progression before death at 6-months and 12-months was 7%. Five patients (8.1%) developed radiation-related neuropathy (grade 1, 2 and 3 in two, one and two cases, respectively). No patient suffered grade 4 or higher late toxicity. The vertebral compression fracture rate was 16%. Three patients (4.8%) eventually underwent kyphoplasty and two patients underwent surgery (3.2%) for vertebral fractures. <h3>Conclusion</h3> Re-irradiation with 40 Gy in 5 fractions seems safe and effective for the salvage of lesions progressing after a previous course of SBRT in a cohort of patients with extensive disease involvement. Prospective randomized trials are needed to determine the optimal dose and fractionation in this clinical scenario.

High-dose salvage re-irradiation in recurrent/progressive adult diffuse gliomas: development of a novel prognostic scoring system

PurposeOver the past two decades, high-dose salvage re-irradiation (re-RT) has been used increasingly in the multimodality management of adults with recurrent/progressive diffuse glioma. Several factors that determine outcomes following re-RT have been incorporated into prognostic models to guide patient selection. We aimed to develop a novel four-tiered prognostic model incorporating relevant molecular markers from our single-institutional cohort of patients treated with high-dose salvage re-RT for recurrent/progressive diffuse glioma. Material and methodsVarious patient, disease, and treatment-related factors impacting upon survival following salvage re-RT were identified through univariate analysis. Each of these prognostic factors was further subdivided and assigned scores of 0 (low-risk), 1 (intermediate-risk), or 2 (high-risk). Scores from individual prognostic factors were added to derive the cumulative score (ranging from 0 to 16), with increasing scores indicating worsening prognosis. ResultsA total of 111 adults with recurrent/progressive diffuse glioma treated with salvage high-dose re-RT were included. We could assign patients into four prognostic subgroups (A=15 patients, score 0–3); (B=50 patients, score 4–7); (C=33 patients, score 8–10); and (D=13 patients, score 11–16) with completely non-overlapping survival curves suggesting the good discriminatory ability. Post-re-RT survival was significantly higher in Group A compared to groups B, C, and D, respectively (stratified log-rank p-value <0.0001). ConclusionThere exists a lack of universally acceptable ‘standard-of-care’ salvage therapy for recurrent/progressive diffuse glioma. A novel four-tiered prognostic scoring system incorporating traditional factors as well as relevant molecular markers is proposed for selecting patients appropriately for high-dose salvage re-RT that warrants validation in a non-overlapping cohort.