Salvage Reirradiation Research Articles

Salvage high-intensity focused ultrasound for residual or recurrent cervical cancer after definitive chemoradiotherapy.

e17524 Background: Approximately 30%-65% of patients have residual disease or subsequent recurrence after completion of chemoradiotherapy (CRT) treatment. The treatment of residual/recurrent cervical cancer in previously irradiated field is challenging and generally associated with a poor prognosis. Local treatments such as salvage surgery and re-irradiation are usually traumatic and have limited efficacy. High intensity focused ultrasound (HIFU) treatment can directly ablate solid tumors without damaging neighboring healthy tissue. However, the HIFU studies for these patients are limited. Over 10 years of experience gained with the management of HIFU in cervical cancer patients with residual disease or recurrence after CRT is reported here. Methods: 153 patients with residual or recurrent cervical cancer in previously irradiated field who received HIFU treatment between 2010 and 2021 were retrospectively analyzed. Adverse effects, survival benefit, and factors affecting prognosis were given particular attention. Results: A total of 36 patients (23.5%) achieved a partial response following HIFU treatment and 107 patients (69.9%) had stable disease. The objective response and disease control rates were 23.5% and 93.5%, respectively. The median progression-free survival (mPFS) and median overall survival (mOS) were 17.0 months and 24.5 months, respectively. Moreover, patients with lesions ≥ 1.40 cm before HIFU treatment and a shrinkage rate ≥ 30% after treatment had a higher mPFS and mOS, and patients with lesions ≤ 1.00 cm after HIFU treatment had a higher mPFS (P < 0.05). All of the treatment-related adverse events were limited to minor complications, which included skin burns, abdominal pain and vaginal discharge. Conclusions: Many cervical cancer patients have few efficacious treatment options following chemoradiotherapy. This study demonstrates that HIFU treatment is likely a preferred option that can safely improve the local control rate and extend survival.

The Role of Interstitial Brachytherapy for Breast Cancer Treatment: An Overview of Indications, Applications, and Technical Notes.

Breast cancer represents the second leading cause of cancer-related death in the female population, despite continuing advances in treatment options that have significantly accelerated in recent years. Conservative treatments have radically changed the concept of healing, also focusing on the psychological aspect of oncological treatments. In this scenario, radiotherapy plays a key role. Brachytherapy is an extremely versatile radiation technique that can be used in various settings for breast cancer treatment. Although it is invasive, technically complex, and requires a long learning curve, the dosimetric advantages and sparing of organs at risk are unequivocal. Literature data support muticatheter interstitial brachytherapy as the only method with strong scientific evidence to perform partial breast irradiation and reirradiation after previous conservative surgery and external beam radiotherapy, with longer follow-up than new, emerging radiation techniques, whose effectiveness is proven by over 20 years of experience. The aim of our work is to provide a comprehensive view of the use of interstitial brachytherapy to perform breast lumpectomy boost, breast-conserving accelerated partial breast irradiation, and salvage reirradiation for ipsilateral breast recurrence, with particular focus on the implant description, limits, and advantages of the technique.

Toxicity of Proton Therapy versus Photon Therapy on Salvage Re-Irradiation for Non-Small Cell Lung Cancer.

This study evaluated the toxicity associated with radiation techniques on curative re-irradiation (re-RT) in patients with thoracic recurrence of non-small cell lung cancer (NSCLC). From 2011 to 2019, we retrospectively reviewed the data of 63 patients with salvage re-RT for in-field or marginal recurrence of NSCLC at two independent institutions. Re-RT techniques using X-ray beams and proton beam therapy (PBT) were also included. Re-RT had a 2-year overall survival (OS) and local progression-free survival of 48.0% and 52.0%, respectively. Fifteen patients experienced grade 3 or higher toxicity after re-RT. The complication rates were 18.2% (4/22) and 26.8% (11/41) in PBT patients and X-ray patients, respectively. Airway or esophageal fistulas occurred in seven patients (11.1%). Fistulas or severe airway obstruction occurred in patients with tumors adjacent to the proximal bronchial tree and esophagus, who underwent hypofractionated radiotherapy (RT) or concurrent chemotherapy, and with a higher dose exposure to the esophagus. In conclusion, salvage re-RT was feasible even in patients with local recurrence within the previous RT field. PBT showed similar survival outcomes and toxicity to those of other techniques. However, thoracic re-RT should be performed carefully considering tumor location and RT regimens such as the fraction size and concurrent chemotherapy.

Bevacizumab increases late toxicity in re-irradiation with image-guided high-dose-rate brachytherapy for gynecologic malignancies.

IntroductionPatients with recurrent gynecologic malignancies having had pelvic irradiation, generally have limited salvage options. This study investigated patients with gynecologic malignancies, who had a history of pelvic irradiation and received salvage re-irradiation using image-guided high-dose-rate brachytherapy (IG-HDR-BT).Material and methodsPatients with gynecologic malignancies, who had a history of previous irradiation and received re-irradiation using IG-HDR-BT for disease recurrences from June 2014 to March 2020 were included in this study.ResultsA total of 37 patients were included in this retrospective analysis. Primary tumor was uterine cervical cancer in 31 patients, endometrial cancer in 5 patients, and vaginal cancer in 1 patient. Median follow-up period of patients who were alive at the time of analysis was 15.4 months (range, 4.1-61.4 months). Two-year overall survival, progression-free survival, and local control were 68.9%, 49.3%, and 67.5%, respectively. Severe late toxicities ≥ grade 3, which were related to re-irradiation, were observed in 9 patients (24.3%). Usage of bevacizumab in the entire course of treatment was associated with development of late ≥ grade 3 fistula formation, bowel perforation, or vaginal ulcer (50% vs. 6.9%, p = 0.013). Tumor size ≥ 2.5 cm was associated with development of late ≥ grade 3 of rectum, bladder, or vaginal toxicities (0% vs. 28%, p = 0.047).ConclusionsIf the recurrent disease was found in small size and there was no history of bevacizumab usage, re-irradiation with IG-HDR-BT could be considered, even in patients with a previous history of pelvic irradiation.

Urinary toxicity after salvage re-irradiation for prostate cancer local failure after definitive radiotherapy: a clinical and dosimetric prognostic factors analysis.

PurposePredictors of long-term toxicity after prostate cancer re-irradiation are scarce. In this study, we retrospectively assessed the impact of clinical/dosimetric data on late genitourinary (GU) toxicity on fourteen radio-recurrent prostate cancer patients treated with salvage radiotherapy (RT).Material and methodsTo identify dose parameters and clinical factors potentially associated to severe long-term GU toxicity, study population was stratified in two groups according to toxicity, including one low-grade group (grade ≤ 2, n = 6) and one high-grade group (grade ≥ 3, n = 8). Dose prescription at primary and salvage-RT in 2 Gy equivalent dose (EQD2Gy) per fraction, treatment techniques, and clinical factors potentially associated to severe GU toxicity were analyzed.ResultsAt salvage-RT, the median EQD2Gy α/β = 3 Gy was significantly higher in the high-toxicity group (85 Gy, range, 71-85 Gy) compared to the low-toxicity group (77 Gy, range, 61-85 Gy) (p = 0.01). All patients treated using salvage-RT with a brachytherapy (BT) boost and with a baseline Framingham risk-score of > 20% (n = 8) developed severe GU toxicity, while none of the remaining patients developed a grade 3 or more GU toxicity (p = 0.0003). V70 > 0 and V75 > 0 of the primary treatment were associated with an increased rate of toxicity.ConclusionsOur analysis shows that the delivery of doses up to 75-80 Gy (EQD2Gy, α/β = 3 Gy) in salvage-RT can be safe in terms of severe GU toxicity avoidance. Furthermore, concomitant cardiovascular comorbidities seem to increase the risk to develop severe GU toxicity.

SBRT as Salvage Re-Irradiation for Isolated In-Field Regional Relapse After Bilateral Breast Cancer – a Case Report

"Stereotactic body radiation therapy (SBRT) is a type of radiotherapy which uses a high radiation dose delivered in a single or a few fractions and is employed with local curative intent for early-stage cancer, relapsed cancer or in the oligometastatic setting. The aim of this case report is to illustrate the potential of this technique in the salvage re-irradiation of a late isolated in field regional relapse after bilateral breast cancer. This is the case of a 65-years-old woman with a metachronous bilateral breast cancer (left side-1998, stage IIB, Luminal type; right side-2010, stage IIA, Her2 positive) who received both chemo- and endocrine systemic therapy, underwent surgery and was irradiated on both sides, with a late solitary recurrence in her left internal mammary node chain (2018) treated by SBRT re-irradiation (40 Gy in 5 fractions). Three years after salvage SBRT, under Palbociclib+Letrozole and thorough follow-up protocol, she is still in clinical complete remission, with a normal CA 15-3 and metabolically inactive residual mass on PET-CT, negative on a recent biopsy. SBRT is becoming a hallmark of oligometastatic disease management and can be invaluable in patients subjected to prior radiotherapy."

Disparities in Use of Salvage Whole Brain Radiation Therapy vs. Salvage Stereotactic Radiosurgery After Initial Stereotactic Radiosurgery for Brain Metastases

Patients undergoing stereotactic radiosurgery (SRS) for brain metastases often relapse and require additional radiation. Due to the paucity of data, the decision to offer salvage re-irradiation with whole brain radiation therapy (WBRT) versus SRS is made on an individual basis. Our objective is to determine the clinical and demographic factors associated with SRS versus WBRT for salvage of first intracranial failure (ICF), i.e., local and/or locoregional failures.We identified a cohort of 374 consecutive patients with brain metastases treated with SRS in the definitive or postoperative setting, at a single institution, from August 2014 to September 2019. Eligible patients received subsequent salvage radiation at our institution with WBRT or SRS at least one month after initial SRS. Clinical and demographic characteristics were retrospectively recorded. Univariate (UVA) and multivariate analyses (MVA) were performed to determine if there was a significant correlation between these factors and the use of salvage SRS versus WBRT. Odds ratios (ORs) and corresponding P-values were estimated from logistic regression model. A survival analysis was also performed to assess the impact of these factors on survival. All tests were two sided and P-value of < 0.05 was used for significance.A total of 110 patients (median age 60, median time to salvage radiation 5.85 months, median follow-up from initial treatment 1.47 years and 0.81 years from salvage treatment) met eligibility criteria for inclusion in this study. 78 patients received SRS and 32 patients received WBRT at the time of first ICF. On UVA the following factors were associated with salvage SRS: having a single new lesion (OR 9.86, P = 0.012), ≥1 stable lesions (OR 5.06, P = 0.001). On UVA the following factors were associated with decreased use of salvage SRS: male gender (OR 0.42, P = 0.044), patient primary language of Spanish (OR = 0.42, P = 0.050), and local progressive lesions (1 lesion OR 0.13, P < 0.001; ≥ 2 lesions, OR 0.10, P = 0.008). On MVA the following factors were associated with decreased use of salvage SRS: male gender (OR = 0.35, P = 0.044) and local progressive lesions (1 lesion OR 0.11, P < 0.001; ≥ 2 lesions, OR 0.11, P = 0.038). Median OS from time of salvage SRS was 1.56 years for the entire cohort. Factors associated with increased survival on MVA included KPS > 70, Stable/absent systemic disease, and receipt of salvage SRS.The strongest factor associated with selection of salvage WBRT vs. SRS for ICF following initial SRS is local progression. There was also found to be a significant disparity in the form of decreased salvage SRS for male patients that remained significant when controlling for other disease and socioeconomic factors. Possible etiologies of this difference could be provider or patient driven but warrant further exploration. In this cohort, salvage SRS was associated with a statistically significant improvement in OS, however, this may also represent a selection bias.Y.S. Soni: None. B.J. Rich: None. D. Kwon: None. W. Zhao: None. D.L. John: None. C.S. Seldon: None. C. Benjamin: None. R. Benveniste: None. R.J. Komotar: None. P. Prieto: None. M. De La Fuente: None. G. Azzam: None. E.A. Mellon: None. T. Diwanji: None.

Brachial Plexus Tolerance to High-Dose Radiation in the Re-Irradiation Setting

<h3>Purpose/Objective(s)</h3> Radiotherapy (RT) is a cornerstone modality in treating head and neck cancers in the primary and salvage settings. Maximum tolerated dose to the brachial plexus and other factors contributing to brachial plexus injury in the re-irradiation setting are poorly understood. To define radiation dose and other clinical factors associated with the brachial plexus injury in patients treated with re-irradiation for recurrent head and neck cancers. <h3>Materials/Methods</h3> We analyzed 47 brachial plexus re-irradiation between 2015 and 2020. A first course of radiation for head and neck cancer, developed recurrent disease, and then underwent salvage re-irradiation. DICOM plans and contours for all patients were reviewed by two authors and via a prospective multidisciplinary chart rounds. Common terminology criteria for adverse events (CTCAE) was used to define the brachial plexus injury after the second course of radiation. We used ROC curves to evaluate the cutoff values. Kaplan-Meier and logistic regression were used to test the correlation between the variables and the outcome. <h3>Results</h3> Median prescription dose from the 1st course was 70 Gy (range: 60-70) and from the 2nd course was 66 Gy (46-70) in 2 Gy per fraction. All patients received photon volumetric modulated arc therapy; 74% received concurrent chemotherapy (CRT) during the 1st course (Cisplatin 30%, Carboplatin +/- Paclitaxel 23% and Cetuximab 21%), 74% received CRT during the 2nd course (Carboplatin/Paclitaxel 40%, Cetuximab 17%, Cisplatin 13% and Nivolumab 4%) and 53% received CRT twice. The median time interval between the two RT courses was 24 months (range, 8-221 months). The median cumulative maximum dose (Dmax) to brachial plexus was 97 Gy (range, 64-144 Gy). At a median follow-up of 9 months (range, 1-47 months), the cumulative incidence of brachial plexopathy (CIBPP) was 17% at 1 year. This consisted of two cases with pain alone, one case with numbness alone, two cases with weakness alone and one case with combination of pain and numbness. The median time to development of symptoms was 8.2 months (range, 1-15 months). Among patients with a Dmax greater than vs less than 106 Gy, the 1-year cumulative incidence of BPP was 42% vs 4% <i>P</i> = 0.005. V80 > 1cc (1-yr CIBPP 34% vs 4% <i>P</i> = 0.03) and V90 > 0.3cc (32% vs 4%, <i>P</i> = 0.046) associated with increased risk of BPP. The use of concurrent cisplatin during re-irradiation was associated with increased risk of BPP (OR 39 CI 4.263-356.81, <i>P</i> = 0.001). Other variables like gender, history of neck surgery, use of other kind of systemic therapy, use of cisplatin during the first course of RT, mean cumulative dose, V60, V70, V100 and the interval between the first and the second courses of radiation were not associated with increased risk of BPP. The 1-year OS was 78% and the 1-year PFS was 52%. <h3>Conclusion</h3> Cumulative incidence of radiation-induced BPP after re-irradiation was 17% at 1 year. Dmax > 106 Gy, higher V80/V90, and the use of concurrent cisplatin during re-irradiation, were associated with increased risk of BPP.

Outcomes of osteosarcoma, chondrosarcoma and chordoma treated with image guided-intensity modulated radiation therapy

Background & purposeTo evaluate the efficacy and toxicity of dose-escalated image guided-intensity modulated radiation therapy (IG-IMRT) in osteosarcoma (OGS), chondrosarcoma (CS) and chordoma (CH) of head and neck (H&N) and pelvis. Methods and MaterialsIn this prospective non-randomized study, 65 patients of H&N or pelvic OGS (24), CS (7) and CH (34) mandating definitive or post-operative radiotherapy from May 2013 to December 2018 were included. Radiotherapy doses in definitive setting were 72.0 Gy for CH and 70.2 Gy for OGS and CS; while in post-operative setting it was 66.6 Gy and 64.8 Gy respectively (at 1.8 Gy per fraction). ResultsPlanned doses of radiotherapy could be completed in 61 (93.8%) patients; with grade III or higher acute and late toxicities of 3% and 0% respectively. With a median follow-up of 52 (range 6–92) months, the five-year actuarial local control (LC) rates were 66% in OGS, 38.1% in CS and 75.9% in CH; while cause-specific survival (CSS) rates were 54.7%, 64.3% and 92.2% respectively. There was no statistically significant difference in outcomes for patients receiving definitive and post-operative radiotherapy. Locally controlled disease at first follow-up after radiotherapy was associated with improved CSS and OS in CS (p = 0.014) and CH (p < 0.001). Radiotherapy resulted in significant and sustained improvement in Musculoskeletal tumour society (MSTS) score and reduction in pain score. Salvage re-irradiation was feasible in local progression after radiotherapy, with good outcomes and tolerability. ConclusionDose-escalated IG-IMRT results in good LC & functional improvement with minimal toxicity in OGS, CS and CH.

Salvage Re-irradiation with Intensity-modulated Radiotherapy, Chemotherapy Combined with Hyperthermia for Local Recurrence of Nasopharyngeal Carcinoma After Chemoradiotherapy.

A sufficient dose of radiation is difficult to administer in re-irradiation for local recurrence of cancer after radiotherapy because of the dose limitation to organs at risk. Re-irradiation cases also include radioresistant tumors that are difficult to control locally, and their prognosis is poor in general. The effect of re-irradiation using intensity-modulated radiotherapy (IMRT) has recently been reported to significantly reduce the dose to organs at risk, and the efficacy of hyperthermia has been reported for radioresistant tumors. We report a case of local recurrence after concurrent chemoradiotherapy treated with salvage re-irradiation using IMRT and chemotherapy combined with hyperthermia in a patient with nasopharyngeal carcinoma, and include a discussion of the literature.

Stereotactic Re-Irradiation for Local Recurrence after Radical Prostatectomy and Radiation Therapy: A Retrospective Multicenter Study.

Simple SummaryStereotactic body radiation therapy remains an understudied treatment option for local recurrence in the prostate bed after prostatectomy followed by radiation therapy. Ablative treatment of local recurrence could avoid or delay androgen deprivation therapy or next-generation antiandrogens. This study suggests that this treatment modality could be a valuable option if confirmed by a prospective study, but long-term toxicity may be a significant limitation.Prostate cancer recurrence in patients previously treated with radical prostatectomy and radiation therapy is challenging. Re-irradiation could be an option, but data regarding efficacy and safety are lacking. We retrospectively evaluated salvage re-irradiation for local recurrence after prostatectomy and external beam radiation therapy. We collected data from 48 patients who underwent salvage reirradiation with stereotactic radiation therapy for local prostate cancer recurrence in the prostatic bed at four French centers. Fifteen patients (31%) were on androgen deprivation therapy during stereotactic radiotherapy. Biochemical response and relapse-free survival were analyzed, and post-treatment toxicities were assessed according to the Common Terminology of Adverse Events criteria. Five patients had grade 3 late bladder toxicity (cystitis), three had grade 3 late incontinence, and one had grade 3 late chronic pain. At three months, 83% of patients had a positive biochemical response. The median follow-up was 22 months. At the end of the follow-up, 21 patients (43%) had a biochemical relapse. The median time to biologic relapse was 27 months. The biochemical relapse rates at 1 and 2 years were 80% and 52%, respectively. In conclusion, salvage re-irradiation for recurrent prostate cancer in the prostate bed may generate significant toxicity rates, and a prospective study with appropriate patient selection is needed to evaluate its effectiveness.

Salvage re-irradiation using stereotactic body radiation therapy for locally recurrent prostate cancer: the impact of castration sensitivity on treatment outcomes

BackgroundAdvances in imaging, biomaterials and precision radiotherapy provide new opportunities to salvage locally recurrent prostate cancer (PC). This study evaluates the efficacy and safety of re-irradiation using stereotactic body radiation therapy (SBRT). We hypothesized that patients with castrate-resistant PC (CRPC) would benefit less from local salvage.MethodsA prospective clinical database was reviewed to extract 30 consecutive patients treated with prostate re-irradiation. Gallium prostate specific membrane antigen (PSMA) ligand positron emission tomography was performed following prostate-specific antigen failure in all patients and biopsy was obtained in 18 patients (60%). Re-irradiation was either focal (n = 13) or whole-gland (n = 17). Endo-rectal balloons were used in twenty-two patients and hydrogel spacers in eight patients. The median prescription dose was 5 fractions of 6.5 (range: 6–8) Gray (Gy).ResultsMedian follow-up was 28 months. Failure occurred in 10 (out of 11) CRPC patients versus 6 (out of 19) castrate-sensitive patients (91% vs. 32%, p = 0.008) after a median of 13 and 23 months, respectively. Metastases occurred in 64% (n = 7) of CRPC patients versus 16% (n = 3) of castrate-sensitive patients (p = 0.007). Two patients experienced local in-field recurrence, thus local control was 93%. The 2 and 3-year recurrence-free survival were 84% and 79% for castrate-sensitive patients versus 18% and 9% for CRPC patients (p < 0.001), and 3-year metastasis-free survival was 90% versus 27% (p < 0.01) for castrate-sensitive and CRPC patients, respectively. Acute grade II and III genitourinary (GU) toxicity occurred in 27% and 3%, and late GU toxicity in 30% and 3%, respectively. No ≥ grade II acute gastrointestinal (GI) toxicity occurred, and only one patient (3%) developed late grade II toxicity.ConclusionsEarly delivery of salvage SBRT for local recurrence is associated with excellent 3-year disease control and acceptable toxicity in the castrate-sensitive phenotype. PSMA imaging for detection of local recurrence and the use of precision radiotherapy with rectal protective devices should be further investigated as a novel salvage strategy for radio-recurrent PC.

Proton Reirradiation for Locoregionally Recurrent Breast Cancer

PurposeLocal-regional recurrence (LRR) of breast cancer after prior adjuvant radiation (RT) can present a clinical challenge. Proton therapy is recommended by the American Society for Radiation Oncology in cases where reirrradiation is needed; however, data are limited. We present the toxicity and outcomes after reirradiation for local-regional recurrence of breast cancer with proton therapy. Methods and MaterialsA single-institution retrospective review identified patients with the following criteria: LRR of breast cancer, prior photon radiation to the same region, proton beam reirradiation, and definitive intent. Surgery or systemic therapy at the time of recurrence was used when indicated. The log-rank test was used to compare Kaplan-Meier survival estimates. Kruskal-Wallis tests were performed to compare worst reported toxicities with clinical variables. ResultsThe population included 27 patients with a history of prior radiation and treated with proton therapy for LRR between 2012 and 2019. The median interval between courses was 9.7 years. Proton reirradiation regimens included whole breast/chest wall (WB/CW) with regional nodal RT (22/27), nodal RT alone (2/27), or WB/CW alone (3/27). The median dose was 51 Gy, and the most common fractionation was 1.5 Gy twice daily. Median follow-up after reirradiation was 16.6 months. Acute grade 3 toxicities included dermatitis in 2 patients and breast pain in 2 patients. Grade 2 or higher late toxicities included 6 G2 rib fractures and 1 G2 brachial plexopathy, 1 G3 dermatitis, 1 G3 breast pain, and 1 G4 dermatitis. Twelve patients had new documented recurrences of which 1 was a second in-field LRR, and there were 7 deaths. ConclusionsProton salvage reirradiation to median 51 Gy in 1.5 Gy twice daily appears to be safe with acceptable acute and late toxicity, and effective with >95% local-regional control.

Stereotactic lung reirradiation for local relapse: A case series

IntroductionLocal recurrence after lung SBRT for early stage NSCLC is rare but its treatment remains a challenge due to limited surgical options. We report a case series of 5 patients treated by stereotactic lung salvage reirradiation for local relapse after a previous lung SBRT. Material and methodsIncluded patients presented an isolated primary lung relapse within at least the 50% isodose of the previous SBRT treatment. Typical reirradiation schedule was 60 Gy in 8 fractions at isodose 80% and was delivered by Cyberknife® using Synchrony® fiducial tracking system. Dose summations were performed to evaluate the safety of the reirradiation. ResultsWe identified 5 patients presenting peripheral lesions. All reirradiated lesions were locally controlled after a median follow-up of 11.1 months (6,7–12,2), while PFS at 6 months was 60% (n = 3). We did not notice any Grade 3 or more acute or late adverse event. ConclusionWe observed encouraging short-term outcome of lung SBRT reirradiation in patients presenting isolated local relapse of an early-stage NSCLC. Further studies are necessary to confirm the safety and efficiency of this salvage treatment approach.

Normal tissue complication probabilities (NTCP) of urethral stricture following salvage SBRT or HDR for periurethral recurrences following prior definitive radiation therapy.

246 Background: SBRT and HDR brachytherapy have emerged as definitive salvage re-irradiation options for men with locally recurrent prostate cancer after prior radiation therapy (RT). Toxicity with re-irradiation remains a concern in this setting, particularly for salvage of periurethral recurrences. We calculated the normal tissue complication probability (NTCP) of urethral stricture following salvage re-irradiation (HDR and SBRT) after previous definitive RT (external beam or HDR) for periurethral recurrences. Methods: Two upfront definitive treatment plans were generated for 5 men with localized prostate cancer: External Beam RT (EBRT1) to a dose of 79.2 Gy in 1.8 Gy fractions and HDR monotherapy (HDR1), 13.5 Gy x 2 implants. Periurethral recurrences were virtually created on diagnostic MRI scans for each of the five men and defined as a recurrent dominant intraprostatic lesion (DIL). Three salvage RT plans were generated for each patient (constraints in Table): HDR salvage (10 Gy whole gland; 13.5 Gy to DIL; 2 implants), SBRTr with maximal rectal sparing (constraints designed for salvage following prior EBRT; 30 Gy in 5 fractions whole gland; 40 Gy in 5 fractions to DIL), and SBRTu with maximal urethral sparing (constraints designed for patients with prior HDR monotherapy; same Rx). DVH data was collected for each plan (previous RT and each salvage approach) and the equivalent uniform dose (EUD) was calculated. NTCP for the urethral stricture in the summed plans (prior definitive treatment + each salvage plan) was calculated by the Lyman-Kutcher-Burman model using the following parameters: (α/β = 5Gy; TD50= 116.7; m = 0.23; n = 0.3). Results: Prescription coverage of 90% of the DIL volume was achieved for each plan. The mean NTCP of urethral stricture for EBRT1 + HDR salvage was 55.2% (range, 52.2-59.1%) and for HDR1 + HDR salvage was 49.2% (42.9-57.5%). For EBRT1 + SBRTr and EBRT1 + SBRTu the NTCP for urethral stricture was 54.0% (50.4-61.0%) and 43.2% (39.4-48.4%), respectively. The NTCP of urethral stricture for HDR1 + SBRTr was 48.1% (41.0-57.2%) and for HDR1 + SBRTu was 37.6% (30.9-44.6%). Conclusions: In this modeling analysis of salvage RT for periurethral recurrences following previous RT (EBRT or HDR monotherapy), the NTCP for urethral stricture was numerically lowest for salvage SBRT using maximum urethral sparing dose constraints in comparison to salvage SBRT with maximum rectal sparing constraints or salvage HDR brachytherapy. This type of analysis lends insight into personalized treatment planning based on previous RT modality and previous dose to organs at risk. Expanded analysis is underway. [Table: see text]

High-dose salvage re-irradiation for recurrent/progressive adult diffuse glioma: healing or hurting?

To report survival outcomes and identify prognostic factors of salvage re-irradiation (re-RT) in recurrent/progressive glioma. Medical records of patients treated with high-dose re-RT as part of multi-modality salvage therapy for recurrence/progression of adult diffuse glioma from 2010 to 2019 were analyzed retrospectively. A total of 111 patients developing recurrent/progressive high-grade glioma after adequate upfront treatment at initial diagnosis were included. The first course of radiotherapy (RT) had been delivered to a median dose of 59.4Gy with an inter-quartile range (IQR) of 54-60Gy. Median time to recurrence/progression was 4.3years (IQR = 2.3-7.4years) while the median time to re-RT was 4.8years (IQR = 3.6-7.9years). Re-RT was delivered with intensity-modulated radiation therapy (IMRT) using 1.8Gy/fraction to a median dose of 54Gy (IQR = 50.4-55.8Gy) for a cumulative median equivalent dose in 2-Gy fractions (EQD2) of 104.3Gy (IQR = 102.6-109.4Gy). At a median follow-up of 14months after re-RT, the 1-year Kaplan-Meier estimates of post-re-RT progression-free survival (PFS) and overall survival (OS) were 42.8 and 61.8%, respectively. Univariate analysis identified histological grade at recurrence/progression; histological subtype; disease-free interval (DFI) and time interval between both courses of RT; performance status at re-RT; dose at re-RT and cumulative EQD2; isocitrate dehydrogenase (IDH) mutation; and O6-methyl-guanine DNA methyl transferase (MGMT) gene promoter methylation as significant prognostic factors. Preserved performance status, longer DFI, prolonged time interval between both courses of RT, and presence of IDH mutation were associated with significantly improved PFS on multi-variate analysis. However, only performance status retained independent prognostic significance for OS on multi-variate analysis. Post-treatment changes were seen in 33 (30%) patients on follow-up imaging, with higher cumulative dose (EQD2 ≥ 104.3Gy) being associated with increased risk of post-re-RT pseudo-progression. This clinical audit reports encouraging survival outcomes and identifies key prognostic factors associated with high-dose salvage re-RT in recurrent/progressive glioma.

Development of a Comorbidity-Based Nomogram to Predict Survival After Salvage Reirradiation of Locally Recurrent Nasopharyngeal Carcinoma in the Intensity-Modulated Radiotherapy Era

PurposeTo assess the impact of comorbidity on treatment outcomes in patients with locally recurrent nasopharyngeal carcinoma (lrNPC) using intensity-modulated radiotherapy (IMRT) and to develop a nomogram that combines prognostic factors to predict clinical outcome and guide individual treatment.MethodsThis was a retrospective analysis of patients with lrNPC who were reirradiated with IMRT between 2003 and 2014. Comorbidity was evaluated by Adult Comorbidity Evaluation-27 grading (ACE-27). The significant prognostic factors (P < 0.05) by multivariate analysis using the Cox regression model were adopted into the nomogram model. Harrell concordance index (C-index) calibration curves were applied to assess this model.ResultsBetween 2003 and 2014, 469 lrNPC patients treated in our institution were enrolled. Significant comorbidity (moderate or severe grade) was present in 17.1% of patients by ACE-27. Patients with no or mild comorbidity had a 5-year overall survival (OS) rate of 36.2 versus 20.0% among those with comorbidity of moderate or severe grade (P < 0.0001). The chemotherapy used was not significantly different in patients with lrNPC (P > 0.05). For the rT3–4 patients, the 5-year OS rate in the chemotherapy + radiation therapy (RT) group was 30.0 versus 16.7% for RT only (P = 0.005). The rT3–4 patients with no or mild comorbidity were associated with a higher 5-year OS rate in the chemotherapy + RT group than in the RT only group (32.1 and 17.1%, respectively; P=0.003). However, for the rT3–4 patients with a comorbidity (moderate or severe grade), the 5-year OS rate in the chemotherapy + RT group vs. RT alone was not significantly different (15.7 vs. 15.0%, respectively; p > 0.05). Eight independent prognostic factors identified from multivariable analysis were fitted into a nomogram, including comorbidity. The C-index of the nomogram was 0.715. The area under curves (AUCs) for the prediction of 1-, 3-, and 5-year overall survival were 0.770, 0.764, and 0.780, respectively.ConclusionComorbidity is among eight important prognostic factors for patients undergoing reirradiation. We developed a nomogram for lrNPC patients to predict the probability of death after reirradiation and guide individualized management.

PO-1009: Salvage Re-irradiation for Recurrent Lung Cancer: Treatment outcomes and toxicity analysis

PO-1009: Salvage Re-irradiation for Recurrent Lung Cancer: Treatment outcomes and toxicity analysis

Salvage Re-Irradiation with Stereotactic Radiotherapy for In-Field Neck Lymph Node Recurrence: A Retrospective Study

Neck lymph node (LN) recurrence in the irradiated field is an important characteristic of treatment failure after primary radiotherapy owing to the lack of standard treatment. Recent technological advances have led to the possibility of achieving highly conformal dose distributions of recurrent tumors using stereotactic radiotherapy (SRT), resulting in high local control (LC) and low toxicity, with reduced dose to organs at risk (OAR). We aimed to investigate the efficacy and safety of SRT for neck LN recurrence after radiotherapy. Between 2008 and 2016, 58 neck LN recurrences after radiotherapy in 18 patients with head and neck cancer were treated using a treatment system specialized for stereotactic irradiation. The nasopharynx (17 lesions), oropharynx (4 lesions), hypopharynx (7 lesions), buccal mucosal (13 lesions), tongue (2 lesions), and larynx (15 lesions) were the primary tumor sites. No patient exhibited recurrences at the primary sites during SRT. The target marginal dose (18–20 Gy) was administered in one fraction. Treatment doses and fractions were determined according to the tumor volume and OAR. If the dose for 10 cm3 of the skin or mucosa exceeded 14 Gy in one fraction because of large tumor volume or if the target area was in close proximity to OAR, the number of fractions was increased to prevent adverse effects, e.g., skin ulcers. Diagnostic imaging techniques, such as CT, MRI, and FDG-PET/CT, were used to evaluate tumor response every 2–3 months after SRT. Kaplan–Meier method was used to calculate overall survival (OS) and LC rates, and log-rank test was used to compare 1-year LC differences as per LN volume. The median follow-up period and target volume was 16 (range, 1–80) months and 1.3 (range, 0.05–91) cm3, respectively. The median previous radiotherapy dose and marginal dose of SRT as equivalent dose delivered in 2-Gy fractions (α/β = 10) was 66 (range, 40–70) Gy and 50 (range, 40–58) Gy, respectively. Moreover, the median interval between completion of prior radiotherapy and SRT was 23.5 (range, 4–69) months and 1-year LC and OS rates were 81% and 61%, respectively. Local recurrence was observed in 12 lesions from nine patients. LC was higher with a target volume ≤ 1.0 cm3 than with a target volume > 1.0 cm3 (p = 0.016). The 1-year LC was higher with a target volume ≤ 1.0 cm3 than with a target volume > 1.0 cm3 (92% vs. 68%, respectively). No significant difference in LC was observed when considering other clinical factors. Regarding the cutaneous region and mucosa, grade ≥3 adverse effects were not observed. One patient with large (91 cm3) and widespread tumor that metastasized the carotid artery before SRT showed fatal bleeding. SRT for neck LN recurrence is safe and feasible in most cases, but the treatment indication should be carefully considered for large and widespread tumors.

Rates Of Radionecrosis In Re-Irradiation Of Brain Metastases Using Hypofractionated Stereotactic Radiotherapy

Improved overall survival rates among brain metastases (BM) patients have led to higher rates of salvage re-irradiation in patients with local failure. Hypofractionated stereotactic regimens are an attractive option due to the possibility of lower rates of radionecrosis (RN). This study aims to determine the incidence and risk factors of RN following re-irradiation with hypofractionated stereotactic radiotherapy (hSRT) and compares the results to the incidence of RN following re-irradiation with single fraction SRS reported in literature. Retrospective chart review was conducted on patients from a single institution who received re-irradiation using hSRT to BMs that previously received stereotactic radiotherapy. Patients who received additional whole brain radiation (WBRT), prior to, or after stereotactic radiotherapy were included. Patient, tumor, treatment characteristics, and follow-up data were collected. MRI and pathology of any lesions resected post-radiotherapy were reviewed to assess for the development of RN and the response to treatment. RN was confirmed through MRI or by surgical resection. Associations between RN and target volume, as well as number of months between stereotactic treatments were examined using logistic regression. Association between RN and use of additional WBRT was examined using relative risk and chi-square tests. A total of 110 metastatic brain lesions in 90 patients received hSRT reirradiation between August 2010 and December 2019. 26.7% (n = 24) of patients also received additional WBRT. The most common histologies were breast (n = 31), NSCLC (n = 30), and melanoma (n = 29). The median volume of lesions was 12.25cc (IQR 4.97 – 25.07cc). The most common fractionation scheme was 25 Gy in 5 fractions (72 lesions). The incidence of local failure was 11.6% and 17.4% at 6 and 12 months, respectively. Incidence of symptomatic RN was 6.15% and 15% at 6 and 12 months, respectively. There was no statistically significant association between symptomatic RN at 12-months and radiation dose (p = 0.40), target volume (p = 0.96), use of additional WBRT (p = 0.74), or number of months between SRT (p = 0.99). The incidence of symptomatic RN following re-irradiation with hSRT is lower compared to re-irradiation with single fraction SRS as reported in literature. hSRT provides an alternative salvage option for treating local failure of BMs to reduce risk of RN while achieving local control.