In-field Recurrence Research Articles

EP.08F.16 Re-Irradiation with Chemotherapy with/without Immunotherapy for In-Field Local Recurrence Among Lung Cancer Patients

EP.08F.16 Re-Irradiation with Chemotherapy with/without Immunotherapy for In-Field Local Recurrence Among Lung Cancer Patients

Localized Radiotherapy for Classic Kaposi's Sarcoma: An Analysis of Lesion Characteristics and Treatment Response.

Classic Kaposi's sarcoma (CKS) is a rare malignancy with diverse clinical presentations, lacking a standard treatment. While localized therapies are commonly used for symptomatic lesions, radiotherapy (RT) has demonstrated effectiveness. This study aims to evaluate the efficacy of RT for treating skin lesions in CKS. A retrospective analysis was conducted on patients with KS treated between April 2012 and January 2024. In total, 69 lesions in 16 patients were included. Treatment response was defined as follows: complete response (CR) indicated the absence of clinically detectable skin lesions and symptoms; partial response (PR) was a reduction in lesion height by more than half or a lighter lesion color compared to before treatment. In-field recurrence was the appearance of new lesions within a previously irradiated field. Logistic regression analysis was used to investigate factors influencing response and in-field recurrence. The median follow-up period was 52 months (range, 3-138 months). The overall response rate was 100%, with 92.8% of the patients achieving CR and 7.2% receiving PR. PR was observed in three patients with five lesions, all of which remained stable. In-field recurrence occurred in two patients with initially advanced disease, and all recurrent lesions responded to RT. No variables were significantly associated with response or in-field recurrence. RT for CKS showed a 100% response rate, with complete symptom relief in all cases. The effectiveness of RT was evident, even in cases involving disseminated lesions. Further research is needed to determine the optimal RT dose and fractionation.

Eleven-Year Experience With Midline Extraperitoneal Retroperitoneal Lymph Node Dissection for Germ Cell Tumors.

A midline extraperitoneal approach for retroperitoneal lymph node dissection (EP-RPLND) has been associated with decreased morbidity compared to the transperitoneal approach. We aimed to review our 11-year experience in patients with germ cell tumors (GCTs) who underwent EP-RPLND at a single institution. All patients with GCT who underwent EP-RPLND between 2010 and 2021 were reviewed. Surgical, perioperative, and oncologic outcomes were reported. A logistic regression model was developed to evaluate variables predictive of early discharge. Oncologic outcomes included 2-year recurrence-free survival (RFS) and recurrence patterns, which were analyzed according to pathology. Overall, 237 patients underwent EP-RPLND, of which 72% were administered in the postchemotherapy (PC) setting. Median follow-up was 16.7 months (interquartile range [IQR] 3.9-39.6). Median size of retroperitoneal disease was 2.8 cm (IQR 1.8-5.4), of which 16 cases were ≥ 10 cm. There were no cases of postoperative ileus or readmission due to small-bowel obstruction. Median hospital stay was 2 days (IQR 1-3). From 2020 to 2021, 73% of patients were discharged on postoperative day 1 and 89% by postoperative day 2. Thirty-one complications occurred, including 4% grade III to IV complications. In the primary setting, 2-year RFS for seminoma and nonseminomatous GCT was 0.93 (95% CI 0.84-1.00) and 0.85 (95% CI 0.72-1.00), respectively. In the PC setting, 2-year RFS for seminoma and nonseminomatous GCT was 0.88 (95% CI 0.74-1.00) and 0.88 (95% CI 0.81-0.95), respectively. Overall, only 7 patients had in-field recurrence. Midline EP-RPLND is safe and associated with rapid gastrointestinal recovery, short hospital stay, and low complication rates. It also demonstrates acceptable oncologic outcomes in the primary and PC settings, with low rates of in-field relapse.

The Predictive Value of Different Glasgow Prognostic Scores and the LabBM Score for Patients With Recurrent Glioblastoma.

The prognostic value of scoring instruments was described for newly diagnosed glioblastoma. This study investigated five instruments in patients with recurrent tumors. Original Glasgow Prognostic Score (oGPS), modified GPS (mGPS), high-sensitivity mGPS (HS-mGPS), high-sensitivity oGPS (HS-oGPS), LabBM score, and 10 other factors were analyzed for progression-free survival (PFS) and overall survival (OS) in 51 patients. On univariate analyses, oGPS 0-1, mGPS 0-1, and LabBM score 0-1.0 were significantly associated with improved OS and showed trends for improved PFS. On multivariate analysis, a trend was found for associations between LabBM score 0-1.0 and better OS. In addition, maximal cumulative diameter ≤40 mm and systemic therapy were independently associated with better PFS and OS, resection with PFS, and in-field recurrence with OS. Lower oGPS, mGPS, and LabBM scores were significantly associated with improved OS on univariate analyses. These instruments may be helpful when designing personalized treatment regimens for patients with recurrent glioblastoma.

Stereotactic Ablative Radiotherapy for T1 to T2 Glottic Larynx Cancer: Mature Results From the Phase 2 GLoTtic Larynx-SABR Trial

PurposeTraditional radiotherapy for early-stage larynx cancer irradiates the whole larynx over 5.5-6 weeks. Phase I data suggest that stereotactic ablative radiotherapy (SAbR) is a viable strategy to reduce the irradiated volume and compress treatment time. This phase II study evaluated the efficacy of gLoTtic larynx SAbR (LT-SABR) in 5 or 16 fractions. MethodsEligibility required stage 0-II squamous cell carcinoma of the glottic larynx. The arytenoid cartilage could not be involved beyond the vocal process, and patients smoking more than one pack-per-day were excluded. The treatment volume consisted of the gross tumor volume, with a 3 mm margin (5 mm craniocaudal) to create the planning target volume (PTV). Patients without active smoking and PTV volume < 10 cc receive 4250 cGy in 5 fractions, twice per week; other patients received 58.08 Gy in 16 daily fractions. The primary endpoint was 2-year incidence of local failure. ResultsTwenty-five patients were accrued to this study, with 21 and 4 treated with 5 and 16 fractions, respectively. The stage distribution was in situ (n=1, 4%), T1a/b (n=16/5, 64%/20%), and T2 (n=3, 12%). The median age was 72 years, with a prior smoking history in 16 (64%) and active smoking in one (4%). At a median follow-up for surviving patients of 3.7 years (IQR 3.1-4.4 years), there have been two in-field recurrences (one in each dose cohort). The cumulative incidences of local failure were 4% (90% CI 0.8% - 20%) and 8% (90% CI 3%-24%) at 1 and 2 years, respectively. There have been no acute or late grade 3+ toxicities in disease-free patients. The median baseline, 6, 12 and 24 month Voice Handicap Index scores were 57 (IQR, 32-69), 28.5 (8-48), 4 (0-12), 7.5 (0-12), and 5 (0-24). ConclusionsHighly conformal stereotactic radiotherapy appears safe and efficacious for early-stage glottic larynx cancer, with encouraging patient-reported. These results need to be interpreted with caution given the small sample size and large non-inferiority margin. Additional follow-up and ultimately comparative studies are necessary to validate this paradigm.

Reirradiation of metastases of the central nervous system: part 2-metastatic epidural spinal cord compression.

An increasing number of patients irradiated for metastatic epidural spinal cord compression (MESCC) experience an in-field recurrence and require a second course of radiotherapy. Reirradiation can be performed with conventional radiotherapy or highly-conformal techniques such as intensity-modulated radiation therapy (IMRT), volumetric modulated arc therapy (VMAT), and stereotactic body radiation therapy (SBRT). When using conventional radiotherapy, a cumulative biologically effective dose (BED) ≤120 calculated with an α/β value of 2 Gy (Gy2) was not associated with radiation myelopathy in a retrospective study of 124 patients and is considered safe. In that study, conventional reirradiation led to improvements of motor deficits in 36% of patients and stopped further symptomatic progression in another 50% (overall response 86%). In four other studies, overall response rates were 82-89%. In addition to the cumulative BED or equivalent dose in 2 Gy fractions (EQD2), the interval between both radiotherapy courses <6 months and a BED per course ≥102 Gy2 (corresponding to an EQD2 ≥51 Gy2) were identified as risk factors for radiation myelopathy. Without these risk factors, a BED >120 Gy2 may be possible. Scoring tools have been developed that can assist physicians in estimating the risk of radiation myelopathy and selecting the appropriate dose-fractionation regimen of re-treatment. Reirradiation of MESCC may also be performed with highly-conformal radiotherapy. With IMRT or VMAT, rates of pain relief and improvement of neurologic symptoms of 60-93.5% and 42-73%, respectively, were achieved. One-year local control rates ranged between 55% and 88%. Rates of myelopathy or radiculopathy and vertebral compression fractures were 0% and 0-9.3%, respectively. With SBRT, rates of pain relief were 65-86%. Two studies reported improvements in neurologic symptoms of 0% and 82%, respectively. One-year local control rates were 74-83%. Rates of myelopathy or radiculopathy and vertebral compression fractures were 0-4.5% and 4.5-13.8%, respectively. For SBRT, a cumulative maximum EQD2 to thecal sac ≤70 Gy2, a maximum EQD2 of SBRT ≤25 Gy2, a ratio ≤0.5 of thecal sac maximum EQD2 of SBRT to maximum cumulative EQD2, and an interval between both courses ≥5 months were associated with a lower risk of myelopathy. Additional prospective trials are required to better define the options of reirradiation of MESCC.

Patterns of recurrence after radiotherapy for high-risk neuroblastoma: Implications for radiation dose and field

BackgroundPrognosis for patients with high-risk neuroblastoma (HR-NBL) is guarded despite aggressive therapy, and few studies have characterized outcomes after radiotherapy in relation to radiation treatment fields. MethodsMulti-institutional retrospective cohort of 293 patients with HR-NBL who received autologous stem cell transplant (ASCT) and EBRT between 1997–2021. LRR was defined as recurrence at the primary site or within one nodal echelon beyond disease present at diagnosis. Follow-up was defined from the end of EBRT. Event-free survival (EFS) and OS were analyzed by Kaplan-Meier method. Cumulative incidence of locoregional progression (CILP) was analyzed using competing risks of distant-only relapse and death with Gray’s test. ResultsMedian follow-up was 7.0 years (range: 0.01–22.4). Five-year CILP, EFS, and OS were 11.9 %, 65.2 %, and 77.5 %, respectively. Of the 31 patients with LRR and imaging review, 15 (48.4 %) had in-field recurrences (>12 Gy), 6 (19.4 %) had marginal failures (≤12 Gy), and 10 (32.3 %) had both in-field and marginal recurrences. No patients receiving total body irradiation (12 Gy) experienced marginal-only failures (p = 0.069). On multivariable analyses, MYCN amplification had higher risk of LRR (HR: 2.42, 95 % CI: 1.06–5.50, p = 0.035) and post-consolidation isotretinoin and anti-GD2 antibody therapy (HR: 0.42, 95 % CI: 0.19–0.94, p = 0.035) had lower risk of LRR. ConclusionsDespite EBRT, LRR remains a contributor to treatment failure in HR-NBL with approximately half of LRRs including a component of marginal failure. Future prospective studies are needed to explore whether radiation fields and doses should be defined based on molecular features such as MYCN amplification, and/or response to chemotherapy.

Combined holmium laser enucleation of the prostate with high-intensity focused ultrasound in treating patients with localized prostate cancer in a prostate with volume > 60 g: Oncological and functional outcomes from single-institution study

ObjectiveTo assess the efficacy and safety of combined High-Intensity Focused Ultrasound (HIFU) and Holmium Laser Enucleation of the Prostate (HoLEP) in treating patients with both localized prostate cancer (PCa) and prostate > 60 g. MethodsAll patients who underwent HIFU for treatment of localized PCa were prospectively enrolled in our study. We reviewed records of patients undergoing procedures from January 2016 to January 2023. For patients with prostate sizes > 60 g, HoLEP was offered before HIFU to prevent worsened urinary symptoms post-treatment. Oncological outcomes—prostatic-specific (PSA) kinetics, recurrence rates, treatment failure - and functional results—Sexual Health Inventory for Men (SHIM), International Prostate Symptoms Score (IPSS), and urinary complications were compared between patients undergoing combined HoLEP and HIFU with those underwent HIFU-monotherapy. ResultsAmong 100 patients, 74 underwent HIFU-monotherapy and 26 underwent the combined HoLEP and HIFU. The majority had intermediate-risk PCa (67%). Pathologic assessment of HoLEP specimens showed no tumor evidence in 57% of cases. In comparison to the HIFU-only group, the combined group exhibited significantly lower PSA metrics across various intervals, however, no differences were found regarding overall and infield recurrences and treatment failure rates. While the combined treatment initially resulted in higher incontinence rates and shorter catheterization durations (P < 0.001), no significant difference in IPSS was observed during subsequent follow-ups. ConclusionHoLEP and HIFU can be safely combined for the treatment of PCa in patients with >60 g prostate volume without compromising early oncological outcomes thereby expanding the therapeutic scope of HIFU in treating patients with localized PCa and large adenomas.

Clinical experience of consolidative radiotherapy for localized metastatic non-small cell lung cancer who showed favorable tumor response after systemic treatment

BackgroundOur study has aimed to assess the effects of consolidative high-dose radiotherapy on clinical outcomes in patients with localized metastatic non-small cell lung cancer (NSCLC) who showed favorable tumor response after systemic treatment.MethodsWe retrospectively reviewed the medical records of 83 patients with localized metastatic NSCLC, who received systemic therapy followed by consolidative local radiotherapy at the Korea University Guro Hospital between March 2017 and June 2022. In the current study, we defined localized metastatic disease as the presence of one to three metastatic sites at the time of diagnosis. And patients who showed favorable tumor response after systemic treatment, including oligo-progressive disease at the thoracic site which was amenable to curative high-dose local radiotherapy, were included. The planned total dose and fraction size mainly depended on the location of lesions.ResultsThe median follow-up time after consolidative radiotherapy was 16 months (range: 5–52 months). The overall 2-year progression-free survival rates were 81.4%. Of 83 patients, only four (4.3%), treated with intensity-modulated radiation therapy, showed an in-field local recurrence. Interestingly, only one patient experienced a local failure among the 20 patients who showed an oligo-progressive disease at the thoracic site on the tumor response evaluation after systemic treatment. Regarding treatment-related pulmonary toxicity, three patients with grade-3 and one patient with grade-4 radiation pneumonitis were presented.ConclusionsIf the disease is sufficiently controlled and localized by systemic therapy, local consolidative radiotherapy is thought to improves local control rates with acceptable treatment-related toxicities in patients with localized metastatic NSCLC, especially those with oligo-progressive disease.

Comparison of different target volume delineation strategies based on recurrence patterns in adjuvant radiotherapy for glioblastoma.

Radiation Therapy Oncology Group (RTOG) and the European Organization for Research and Treatment of Cancer (EORTC) recommendations are commonly used guidelines for adjuvant radiotherapy in glioblastoma. In our institutional protocol, we delineate T2-FLAIR alterations as gross target volume (GTV) with reduced clinical target volume (CTV) margins. We aimed to present our oncologic outcomes and compare the recurrence patterns and planning parameters with EORTC and RTOG delineation strategies. Eighty-one patients who received CRT between 2014 and 2021 were evaluated retrospectively. EORTC and RTOG delineations performed on the simulation computed tomography and recurrence patterns and planning parameters were compared between delineation strategies. Statistical Package for the Social Sciences (SPSS) version 23.0 (IBM, Armonk, NY, USA) was utilized for statistical analyses. Median overall survival and progression-free survival were 21 months and 11 months, respectively. At a median 18 month follow-up, of the 48 patients for whom recurrence pattern analysis was performed, recurrence was encompassed by only our institutional protocol's CTV in 13 (27%) of them. For the remaining 35 (73%) patients, recurrence was encompassed by all separate CTVs. In addition to the 100% rate of in-field recurrence, the smallest CTV and lower OAR doses were obtained by our protocol. The current study provides promising results for including the T2-FLAIR alterations to the GTV with smaller CTV margins with impressive survival outcomes without any marginal recurrence. The fact that our protocol did not result in larger irradiated brain volume is further encouraging in terms of toxicity.

Excellent long-term pain response and local control following postoperative radiotherapy in patients with multiple myeloma.

Multiple myeloma is associated with osteolytic bone lesions, often requiring surgery of the spine and postoperative radiotherapy (RT). Although common, data for clinical and informed decision-making are sparse. In this monocentric retrospective study, we aim to report the outcome of patients who underwent spinal surgery and postoperative RT due to multiple myeloma. Atotal of 54patients with multiple myeloma who underwent prior spinal surgery and postoperative RT at our institution between 2009 and 2020 were analyzed. Spinal instability neoplastic score (SINS) and Bilsky score, posttherapeutic adverse events, clinical data, and outcomes were collected and analyzed. The primary endpoint of this study was overall survival (OS), secondary endpoints were progression-free survival (PFS), pain response, local control, and skeletal-related events (SRE). The 3‑ and 5‑year overall survival (OS) was 74.9% (95% confidence interval [CI]: 63.5-88.4%) and 58% (95% CI: 44.5-75.6%), respectively. Median survival was not reached and 75% survival was 34.3months (95% CI: 28.7-95.4 months). Median follow-up was 63months (95% CI: 49-94months). The number of patients with good to adequate performance status (Karnofsky performance score [KPS] ≥ 70) significantly increased after surgery (p < 0.01). We observed no grade3/4 toxicity and only 13 (24%) grade1/2 adverse events. Two patients (4%) experienced SRE. Overall, 92% of patients reported reduced pain after radiotherapy, with 66% reporting complete pain response. There was no difference in pain response between patients with different Bilsky scores. Bisphosphonate therapy and lower Bilsky score at the start of RT were associated with improved OS in univariate analysis (all p < 0.05). Multivariate Cox regression confirmed aBilsky score of2 or3 as an independent negative prognostic factor (HR 3.89; 95CI 1.4-10.7; p < 0.01). We observed no in-field recurrences. In this study, we were able to show that the current standard of RT after spinal surgery of osteolytic lesions is safe. In addition, we observed avery low rate of SRE (4%) and no in-field recurrences, demonstrating the local efficacy of RT in multiple myeloma patients. Higher Bilsky scores were associated with worse OS in multivariate analysis, but had no effect on pain response.

Irreversible Electroporation (IRE) for Prostate Cancer (PCa) Treatment: The State of the Art.

We evaluated the most recent research from 2000 to 2023 in order to deeply investigate the applications of PCa IRE, first exploring its usage with primary intent and then salvage intent. Finally, we discuss the differences with other focal PCa treatments. In the case of primary-intent IRE, the in-field recurrence is quite low (ranges from 0% to 33%). Urinary continence after the treatment remains high (>86%). Due to several different patients in the studies, the preserved potency varied quite a lot (59-100%). Regarding complications, the highest occurrence rates are for those of Grades I and II (20-77% and 0-29%, respectively). Grade III complications represent less than 7%. Regarding the specific oncological outcomes, both PCa-specific survival and overall survival are 100%. Metastasis-free survival is 99.6%. In a long-term study, the Kaplan-Meier FFS rates reported are 91% at 3 years, 84% at 5 years, and 69% at 8 years. In the single study with salvage-intent IRE, the in-field recurrence was 7%. Urinary continence was still high (93%), but preserved potency was significantly lower than primary-intent IRE patients (23%). In addition, Grade III complications were slightly higher (10.8%). In conclusion, in males with localized low-intermediate-risk prostate cancer, IRE had an excellent safety profile and might have positive results for sexual and urinary function.

Contribution of Enhanced Locoregional Control to Improved Overall Survival with Consolidative Durvalumab after Concurrent Chemoradiotherapy in Locally Advanced Non-Small Cell Lung Cancer: Insights from Real-World Data.

This study aimed to assess the real-world clinical outcomes of consolidative durvalumab in patients with unresectable locally advanced non-small cell lung cancer (LA-NSCLC) and to explore the role of radiotherapy in the era of immunotherapy. This retrospective study assessed 171 patients with unresectable LA-NSCLC who underwent concurrent chemoradiotherapy (CCRT) with or without consolidative durvalumab at Asan Medical Center between May 2018 and May 2021. Primary outcomes included freedom from locoregional failure (FFLRF), distant metastasis-free survival (DMFS), progression-free survival (PFS), and overall survival (OS). Durvalumab following CCRT demonstrated a prolonged median PFS of 20.9 months (p=0.048) and a 3-year FFLRF rate of 57.3% (p=0.008), compared to 13.7 months and 38.8%, respectively, with CCRT alone. Furthermore, the incidence of in-field recurrence was significantly greater in the CCRT-alone group compared to the durvalumab group (26.8% vs. 12.4%, p=0.027). While median OS was not reached with durvalumab, it was 35.4 months in patients receiving CCRT alone (p=0.010). Patients positive for programmed cell death ligand 1 (PD-L1) expression showed notably better outcomes, including FFLRF, DMFS, PFS, and OS. Adherence to PACIFIC trial eligibility criteria identified 100 patients (58.5%) as ineligible. The use of durvalumab demonstrated better survival regardless of eligibility criteria. The use of durvalumab consolidation following CCRT significantly enhanced locoregional control and OS in patients with unresectable LA-NSCLC, especially in those with PD-L1-positive tumors, thereby validating the role of durvalumab in standard care.

Is atotal dose of 54Gy with radiochemotherapy sufficient for treatment of intermediate-risk volumes in nasopharyngeal cancer?

The mainstay treatment of nasopharyngeal cancer (NPC) is radiation therapy (RT). The doses and volumes may differ from center to center. Most studies and guidelines recommend atotal dose of 60 Gy for elective nodal and peritumoral volume treatment. This retrospective analysis aimed to analyze whether adose reduction to 54 Gy to this volume would be associated with ahigher risk of recurrence. Atotal of 111patients treated by intensity-modulated radiotherapy (IMRT) and concurrent chemotherapy were retrospectively analyzed. The recurrent tumor volume was classified as "in field" if 95% of the recurrent volume was inside the 95% isodose, as "marginal" if 20-95% of the recurrence was inside the 95% isodose, or as "outside" if less than 20% of the recurrence was inside the 95% isodose. Median follow-up was 67months (range 6-142). The 2‑ and 5‑year overall survival (OS) rates were 88.6% and 70%, respectively. The 2‑year locoregional control (LRC), disease-free survival (DFS), and distant metastasis-free survival (DMFS) were 93.3%, 89.3%, and 87.4%, and the 5‑year LRC, DFS, and DMFS were 86.8%, 74%, and 81.1%, respectively. Ten patients (9%) had alocal and or regional recurrence. Half of the patients with locoregional failure had in-field recurrences. For primary tumor, there was no recurrence in the volume of 54 Gy. For regional lymph node volume, recurrence was detected in two (1.8%) patients in the volume of 54 Gy. These retrospective data suggest that adose reduction may be possible for intermediate-risk volumes, especially for the primary site.

Patient Selection and Outcomes for Hypofractionated Accelerated Radiation and Concurrent Chemotherapy for Non–Small-Cell Lung Cancer

Purpose/ObjectivesAdoption of hypofractionated accelerated radiation therapy (HART) with concurrent chemotherapy has been limited by toxicity concerns. We aimed to describe outcomes of patients treated with HART and concurrent chemotherapy and to evaluate dosimetry to organs at risk to guide patient selection. Materials/MethodsWe evaluated a retrospective cohort of NSCLC patients treated with concurrent chemotherapy with HART (>2.2 Gy per fraction) or standard fractionated radiation therapy (SFRT; 2-2.2 Gy fractions). Dosimetric parameters to key organs at risk were compared, and toxicity, patterns of recurrence and survival were calculated for the cohorts. ResultsFifty-three patients treated with HART were compared with 100 patients treated with SFRT. Median dose per fraction for the HART cohort was 2.75 Gy (range 2.4-3 Gy). HART patients had significantly lower doses to the lung, heart, and esophagus due to patient selection. The HART group and had rates of grade 2+ pneumonitis (9.4 vs. 19%, P = .16) and grade 2+ esophagitis (20.8 vs. 45%, P < .01) that compared favorably to SFRT. Cumulative incidence of in-field recurrence trended lower in the HART cohort (7.6% vs. 23.1%, P = .058). Among the HART group, 88.7% (47/53) met the newly proposed lung constraints based on the degree of hypofractionation ConclusionIn select patients with favorable dosimetry to organs at risk, definitive HART with concurrent chemotherapy achieved excellent local control with low toxicity. These results are being used to inform a prospective study on the safety and efficacy of HART with concurrent chemotherapy for select NSCLC patients.

Long-Term Follow-Up of Patients with Conjunctival Lymphoma after Individualized Lens-Sparing Electron Radiotherapy: Results from a Longitudinal Study.

Irradiation with electrons is the primary treatment regime for localized conjunctival low-grade lymphomas. However, radiation-induced cataracts are a major cause of treatment-related morbidity. This study investigates whether lens-sparing electron irradiation produces sufficient disease control rates while preventing cataract formation. All consecutive patients with strictly conjunctival, low-grade Ann Arbor stage IE lymphoma treated with superficial electron irradiation between 1999 and 2021 at our department were reviewed. A total of 56 patients with 65 treated eyes were enrolled with a median follow-up of 65 months. The median dose was 30.96 Gy. A lens-spearing technique featuring a hanging rod blocking the central beam axis was used in 89.2% of all cases. Cumulative incidences of 5- and 10-year infield recurrences were 4.3% and 14.6%, incidences of 5- and 10-year outfield progression were 10.4% and 13.4%. We used patients with involvement of retroorbital structures treated with whole-orbit photon irradiation without lens protection-of which we reported in a previous study-as a control group. The cumulative cataract incidence for patients treated with electrons and lens protection was significantly lower (p = 0.005) when compared to patients irradiated without lens protection. Thus, electrons are an effective treatment option for conjunctival low-grade lymphomas. The presented lens-sparing technique effectively prevents cataract formation.

The Role of Radiation Therapy in the Management of Gray Zone Lymphoma.

Gray zone lymphoma (GZL) is a relatively rare disease predominantly affecting young adults with purportedly poor outcomes with current treatment approaches. The role of radiation therapy (RT) in the management of GZL is not well established. This is the largest study to report on the outcomes of GZL patients treated with and without RT. A retrospective review of 30 patients with GZL treated across 3 institutions from 2009 to 2021 was performed. Event-free survival (EFS) was defined from initiation of frontline chemotherapy (CHT) to disease progression/relapse, initiation of salvage therapy, or death. Local control (LC) was defined from RT start date to in-field recurrence. The median age was 32 (range: 18-86) years, and 16 (53%) patients had early stage (I-II) disease. Bulky mediastinal disease was present in 63% of patients, and the median tumor diameter was 10 (range: 1.5-18) cm. Patients received ABVD (20%), RCHOP (33%), or REPOCH (47%) as frontline CHT. Among 25 patients with interim PET/CT scan, there were 6 rapid early responders and 14 slow early responders (SER), with 2-year EFS of 33% and 24%, respectively (p = 0.13). After the completion of CHT, 15 (50%) patients achieved complete response (CR) and 10 (33%) achieved partial response (PR), with 2-year EFS of 46% and 10%, respectively (p = 0.004). RT was given to 9 patients in CR (n = 3) or in PR (n = 6). The median RT dose was 36 (30.6-48.6) Gy, at 1.8-2 Gy/fraction. Those receiving RT had bulkier disease at diagnosis (p = 0.049) and lower rates of CR following CHT (p = 0.03). After RT, 3/6 (50%) PR patients converted to CR. At a median follow-up of 4 years, the 2-year EFS was 26% for all patients, 33% for RT and 23% for noRT (p = 0.44). Among patients who did not receive upfront RT and experienced progression (n = 17), 16 (94%) relapsed in pre-existing sites. The 5-year OS was 80% for all patients, 88% for RT and 78% for no RT (p = 0.63). Patients who achieved PR to CHT and received RT had better 2-year EFS (17% vs 0%, p = 0.007) compared to patients who did not receive RT. Similarly, patients with SER who received RT had superior 2-year EFS (33% vs 13%, p = 0.038). Patients with bulky mediastinal disease had a 2-year EFS of 43% with RT and 11% without RT (p = 0.08). After 1st line treatment, 22 (73%) patients relapsed and 18 were successfully salvaged with a sustained CR. The most common salvage regimen involved high dose CHT followed by hematopoietic cell transplantation (HCT) (n = 15). RT was given for 7 patients in the relapsed/refractory setting (consolidative peri-HCT n = 4; definitive salvage n = 3) and 5 (71%) achieved a sustained CR. Among the 16 patients who received RT in the upfront (n = 9) or salvage (n = 7) setting, 3 patients experienced in-field recurrence translating to 2-year LC of 79%. GZL patients have high risk of relapse and maximal upfront combined modality therapy should be considered. RT provides good local control and improves EFS particularly for SER, PR, and bulky mediastinal disease.

Characterizing First Events in LA-NSCLC Patients Treated with Chemoradiotherapy

Definitive chemoradiotherapy (CRT) is a standard treatment for locally advanced non-small cell lung cancer (LA-NSCLC). After treatment, patients are at risk for local disease recurrence, developing new sites of disease, and death without disease recurrence. Here, we characterize the rates of these events in a modern patient cohort and explore risk factors for each event. The hypothesis is that these rates and risk factors will better inform treatment strategies for local intensification and systemic therapy. We reviewed patients who underwent staging PET/CT and were treated for LA-NSCLC with definitive CRT at our institution between 2010 and 2022. Competing risks analyses were performed to calculate rates of disease progression and death without disease progression. Competing risks analyses were repeated after dividing disease progression into in-field recurrence versus out-of-field progression and after subdividing in-field recurrences into progression of high-risk (large) tumors or lymph nodes (defined as having metabolic tumor volume [MTV] >20 cc on staging PET/CT) versus progression of low-risk (small) tumors or lymph nodes. Predictors of each event type were identified using univariate and multivariable Fine and Gray competing risks regressions. A total of 210 patients met inclusion criteria, and the median follow-up duration is 43 months. Median age was 68 (IQR 60 to 74), and 77% of patients had ECOG performance status 0-1. Median progression-free survival and overall survival durations are 13 and 40 months, respectively. The 3-year cumulative incidence rate (CIR) of disease progression was 58%, and the 3-year CIR of death without disease progression was 18%. The 3-year CIR for out-of-field disease progression was 44%, and the 3-year CIR for in-field recurrence was 14%. The 3-year CIR for in-field recurrence of high-risk lesions was 11%, and the 3-year CIR for low-risk lesions was 4%. Multivariable analyses examining predictors of out-of-field progression revealed two statistically significant factors: total disease burden on PET (SHR 1.03 per 10 cc, p = 0.013) and durvalumab receipt (SHR 0.60, p = 0.031). Multivariable analyses also revealed two predictors of death without disease progression: age (SHR 1.06 per year, p = 0.018) and ECOG performance status (SHR 1.81, p = 0.012). For LA-NSCLC patients treated with definitive CRT, we found that developing new sites of disease is the most common first event, followed by death without disease recurrence. In-field disease recurrence is relatively uncommon, particularly when treating relatively small tumors and lymph nodes. These findings may inform prioritization of strategies to improve systemic therapy, intensify local therapy, and minimize treatment-related toxicity.

Long-Term Outcomes of Non-Vestibular Cranial Nerve Schwannomas Treated with Fractionated Stereotactic Radiotherapy and Stereotactic Radiosurgery

Non-vestibular cranial nerve schwannomas (NVCNS) are rare tumors that account for approximately 10% of cranial nerve schwannomas. They are commonly treated with radiation therapy (XRT) due to their location often precluding safe resection. We examined the long-term outcomes of NVCNS treated with XRT as primary management and for post-operative salvage. We conducted a retrospective review of patients with NVCNS treated with fractionated stereotactic radiation therapy (FSRT) or Gamma Knife Stereotactic Radiosurgery (GK-SRS) from 1996 to 2018 at our institution. We examined patient demographics, cranial nerve (CN) involvement, CN function pre-/post-XRT, treatment volume (TV), toxicity, surgery pre-XRT, and local control. Kaplan-Meier analysis was performed for evaluation of local control. We identified 66 patients (38 female, 28 male) with NVCNS, a portion of whom had tumors involving more than one cranial nerve. Forty-six (69.7%) were treated with FSRT (median dose 50.4 Gy in 1.8 Gy/fraction; range 45-54 Gy), and 20 (30.3%) with GK-SRS (median dose 12 Gy; range 12-15 Gy). Median follow-up time was 92.5 months (5-306). Median Karnofsky Performance Status was 90 (70-100). Median age at start of XRT was 45 years old (15-92). Prior to XRT, 34.8% (23) of patients had surgical resection, with median time from surgery to XRT of 4.25 months (0.5-130 months). Median treatment volume was 4.72 cc (0.26-29). The cranial nerve most commonly involved was CN V (48.4%), followed by CN X (15.2%), CN VII (13.6%), CN VI (6.1%), CN XII (6.1%), CN III (6.1%), and CN IX (3%). Twenty-nine (43.9%) patients experienced grade 1 acute toxicity during treatment. Six (9%) patients experienced grade 1 chronic toxicity. No grade 2 or higher acute or chronic toxicity was observed. No significant difference in rates of acute or chronic toxicity was observed between patients treated with GK-SRS vs. FSRT. Post-XRT, 37 patients (56.1%) had improvement in CN function/symptom, 24 patients (36.3%) had stable function/symptoms, and 5 patients (7.6%) had worsening function/symptoms. Local control at one and five years was 100%. In-field recurrence was observed in one patient (1.5%), at 9 years post-XRT. For salvage this patient was treated with a second course of FSRT to the recurrent tumor. Our large institutional series with long term follow up showed excellent local control of NVCNS treated with FSRT or GK-SRS both for primary management and post-operative salvage. Treatment is well tolerated, with high rates of preservation or improvement of CN function, and minimal acute and chronic toxicity.

Proton Re-Irradiation with Concurrent Hyperthermia in Patients with Recurrent Breast Cancer

The aim of this study is to evaluate the safety and effectiveness of proton re-irradiation with concurrent hyperthermia in the treatment of recurrent breast cancer. We retrospectively identified patients previously treated with photon whole breast or chest wall irradiation for a primary breast cancer at our institution, who subsequently developed a histologically-confirmed locoregional recurrence or new ipsilateral primary breast cancer and underwent proton chest wall re-irradiation with concurrent hyperthermia as part of definitive treatment. Acute toxicity was evaluated once weekly while on-treatment and at 2 weeks and 3 months post-treatment. Toxicities were graded according to CTCAE v4.0. Fifteen patients received proton re-irradiation with concurrent superficial hyperthermia at our institution from August 2018 to December 2022. Median interval between radiation treatment courses was 7.7 years (range 1-30 years). Four patients (26%) had gross, unresected disease at the time of re-treatment. The median initial radiation dose, re-irradiation dose, and cumulative EQD2 was 60.4 Gy (50.6-61.2 Gy), 60 Gy (RBE) (45-66 Gy (RBE)), and 120 Gy (RBE) (103-126 Gy (RBE)), respectively. Patients received a median of 9 (3-14) concurrent hyperthermia treatments delivered twice weekly, and 13 patients (87%) received seven or more hyperthermia treatments. Median toxicity follow-up was 9 months (0-36 months). Acute grade 3 toxicities included two patients (13%) with grade 3 dermatitis, both of which resolved with conservative management within 3 months of treatment completion. Chronic grade 2 or higher toxicities included two grade 2 hyperpigmentation, one grade 3 induration, one grade 2 telangiectasia, and one grade 2 rib fracture. There were no grade 4-5 acute or late toxicities. There was one in-field local recurrence and one regional recurrence outside of the re-irradiation field. Both patients had gross, unresected disease at the time of re-irradiation. Two patients (13%) developed distant disease. Proton re-irradiation with concurrent hyperthermia is feasible and well-tolerated in the re-treatment of breast cancer. Further studies are warranted to determine long-term toxicity and oncologic outcomes.