Worse Local Control Research Articles

Local control and toxicity after stereotactic radiotherapy in brain metastases patients and the impact of novel systemic treatments

Background and purposeTreatment modalities for patients with brain metastases consist of surgery, radiotherapy, and systemic treatments such as immunotherapy and targeted therapy. Although much is known about local control of brain metastases after radiotherapy and surgery alone, more understanding is needed of the additional effect of new systemic treatments. Our study presents real-world data about the combined effects of different local and systemic treatment strategies on local response of irradiated brain metastases. Materials and methodsWe performed a retrospective consecutive cohort study of patients that presented with brain metastases in our institution between June 2018 and May 2020, reporting the impact of radiotherapy alone versus radiotherapy combined with systemic treatment on local control of irradiated brain metastases and toxicity. Chemotherapy and targeted therapy were temporarily discontinued around irradiation. Results262 consecutively treated patients were included in the study. Median time to local failure of irradiated brain metastases was 18 months (IQR 9–34), median overall survival was 20 months (IQR 10–36). 211 (81 %) patients received systemic treatment. Patients with breast cancer had a worse local control (HR 2.3, 95 % CI 1.0–5.0, p = 0.038), as did patients without any systemic treatment (HR 2.1, 95 % CI 1.1–4.3, p = 0.034). Symptomatic radiation necrosis occurred in 36 (14 %) patients. A diameter > 2.5 cm was associated with a higher risk of radiation necrosis. No association was found between systemic treatment in combination with local radiotherapy and symptomatic radiation necrosis. ConclusionPatients who received any form of systemic treatment had better local control after stereotactic radiosurgery for brain metastases. We did not find an association between systemic treatment and the incidence of radiation necrosis.

Predictive capacity for local disease control of neogenin-1 (NEO1) transcriptional expression in patients with head and neck squamous cell carcinoma.

To analyze the predictive capacity for local disease control of the transcriptional expression of neogenin-1 (NEO1) gene in patients with head and neck squamous cell carcinoma (HNSCC). A retrospective study was performed on tumor biopsies from 107 patients with HNSCC treated surgically. The transcriptional expression of NEO1 was determined by RT-PCR. NEO1 transcriptional expression value was categorized according to local disease control by recursive partitioning analysis. Lower NEO1 transcriptional expression was associated with worse local control after surgical treatment. Patients with lower NEO1 expression (n = 25, 23.4%) had a 5-year local recurrence-free survival of 61.8% (95% CI: 42.1-81.5%), while patients with higher NEO1 expression (n = 82, 76.6%) had a 5-year local recurrence-free survival of 85.6% (95% CI: 77.6-93.6%), (P = 0.003). According to the result of multivariable analysis, patients with lower NEO1 expression had a 2.7-fold increased risk of local tumor recurrence (95% CI: 1.0-7.0, P = 0.043) compared to patients with higher NEO1 expression. HNSCC patients with a lower transcriptional expression of NEO1 have a significantly higher risk of local recurrence after surgical treatment.

Long-Term Outcomes of Surgery and Radiation Treatment for Adult Patients with Craniopharyngioma

Treatment of craniopharyngioma typically entails gross total resection (GTR) or subtotal resection with adjuvant radiation (STR-RT). We analyzed outcomes in adults with craniopharyngioma undergoing GTR versus STR-RT. This retrospective study enrolled 115 patients with craniopharyngioma in 5 institutions. Patients with STR received postoperative RT with stereotactic radiosurgery or fractionated radiation therapy per institutional preference and ability to spare optic structures. Median age was 44 years (range, 19-79 years). GTR was performed in 34 patients and STR-RT was performed in 81 patients with median follow-up of 78.9 months (range, 1-268 months). For GTR, local control was 90.5% at 2 years, 87.2% at 3 years, and 71.9% at 5 years. For STR-RT, local control was 93.6% at 2 years, 90.3% at 3 years, and 88.4% at 5 years. At 5 years following resection, there was no difference in local control (P= 0.08). Differences in rates of visual deterioration or panhypopituitarism were not observed between GTR and STR-RT groups. There was no difference in local control in adamantinomatous and papillary craniopharyngioma regardless of treatment. Additionally, worse local control was found in patients receiving STR-RT who were underdosed with fractionated radiation therapy (P= 0.03) or stereotactic radiosurgery (P= 0.04). Good long-term control was achieved in adults with craniopharyngioma who underwent STR-RT or GTR with no significant difference in local control. First-line treatment for craniopharyngioma should continue to be maximal safe resection followed by RT as needed to balance optimal local control with long-term morbidity.

Higher area deprivation index is associated with poorer local control and overall survival in non-metastatic nasopharyngeal carcinoma.

Neighborhood socioeconomic deprivation impacts outcomes in various cancers. We examined this association in nasopharyngeal carcinoma (NPC) patients using the area deprivation index (ADI). We conducted a single-institution retrospective cohort study on NPC patients treated with definitive radiotherapy from 1980 to 2023. ADI was used as the primary exposure measure. Higher ADI indicates higher levels of socioeconomic deprivation. Of 561 patients, those with higher ADI (6-10 vs. 1-5) presented more commonly with AJCC stage III/IV compared to I/II (87% vs. 76%, p = 0.03). Increasing ADI decile score correlated with poorer overall survival (HR 1.14, 95% CI 1.01-1.28, p = 0.04). Local control was worse in patients from the most deprived quartile in the cohort ADI 5-10 (HR 2.11, 95% CI 1.01-4.41, p = 0.05). NPC patients from more disadvantaged neighborhoods undergoing radiotherapy had worse local control and survival outcomes. Interventions to address structural determinants of health and neighborhood disparities may improve these outcomes.

Treatments and Prognosis of the Breast Ductal Carcinoma In Situ

IntroductionWith progress in treatments, breast ductal carcinoma in situ (DCIS) outcomes have substantially improved. However, as various treatment methods are used in different countries and institutions, consensus on the optimal treatment method is lacking. This study aimed to analyze the prognostic factors and provide a reference for optimizing the clinical treatment of DCIS. Patients and MethodsThis retrospective clinical study collected data from DCIS patients at the Sun Yat-sen University Cancer Center from 2010 to 2017. The Kaplan–Meier method and Cox regression model were used to assess disease-free survival (DFS), overall survival (OS), and local control (LC) rates. ResultsAmong the 483 included patients, 83.6% (404) underwent mastectomies. The median follow-up time was 101 months. The number of patients undergoing breast-conserving surgery (BCS) with radiotherapy has gradually increased. Axillary lymph node dissection was the main surgery performed from 2010 to 2015, and the proportion of sentinel lymph node biopsies (SLNBs) has increased. LC and DFS rates with BCS without radiotherapy were significantly lower than those with mastectomy (P = .002; P < .001). Additionally, the patients who did not undergo axillary surgery had worse LC and OS rates than those who underwent SLNB (P = .028 and P = .038). Endocrine therapy (ET) or its duration had no significant effect on prognosis. ConclusionIn conclusion, BCS without radiotherapy and lack of axillary surgery were independent prognostic factors. We recommend performing BCS with radiotherapy and SLNB more in clinical practice, as well as shortening the ET duration.

Outcomes of Patients with Transformed Diffuse Large B-Cell Lymphoma (DLBCL).

There is limited data regarding the results of treating transformed Diffuse Large B-Cell Lymphoma, including the influence of radiation therapy on their overall prognosis. Thus, we aimed to investigate the clinical outcomes of transformed DLBCL patients treated at a single institution. We reviewed clinical features and outcomes of 27 patients with biopsy confirmed transformed Diffuse Large B-cell Lymphoma (DLBCL) treated at a single institution from 2005 and 2014. Response to therapy was based on the Deauville criteria. Kaplan-Meier method was used to estimate time to event outcomes and compared using log-rank tests. Associations between local recurrence and relevant clinical variables were analyzed using logistic regression. The median age of patients was 63 (43-84). Eleven patients (40.7%) presented with bulky disease. The majority of patients (n = 16, 59.3%) had the activated B-cell (ABC) subtype, while 11 (40.7%) patients had germinal center B-cell (GCB) subtype. Most of the patients had early-stage disease 19 (70.4%). Double- and triple-hit expression was noted in 6 (22.2%) and 3 (11.1%) patients, respectively. The median international prognostic index (IPI) was 2. Median follow up was 37 months (range 2-168). Twelve (44.4%) patients received consolidative RT after systemic therapy with a median dose of 36 Gy (30-45). At 72 months, our RT cohort had an overall survival (OS), relapse-free survival (RFS) and local control (LC) rates of 63%, 64% and 81%, respectively. The OS did not differ between patients that received RT compared to those who did not (p = 0.124), although RT conferred statistically significant improvement in OS on MVA (HR 0.07; 95% CI, 0.007 to 0.718; p = 0.025). In the group that received RT, local control was worse among patients with double or triple-hit disease (p = 0.034). Patients with transformed Diffuse Large B-cell Lymphoma treated with RT may have better outcomes than patients who did not receive RT. Presence of translocation (double-hit and/or triple-hit lymphomas) was significantly associated with worse local control in our RT cohort.

Favorable Toxicity and Local Control with Ultrahypofractionated Radiation Therapy (UH-RT) for Melanoma of the Lower Genital Tract (LGT)

To report our experience using UH-RT +/- immunotherapy (IO) in women with melanoma of the LGT. We retrospectively identified 23 patients who received UH-RT to primary tumor for vulvovaginal melanoma from 2012 to 2022. Median age was 69 years (IQR: 62-76). Stage included localized, node positive, or metastatic. 18 (78%) had tumors involving the vagina/cervix and 5 (22%) had vulvar tumors. 6 patients had c-KIT mutations; 13 patients were wild-type; 4 patients were unknown. 12 (52%) were treated at initial presentation (cohort A) and 11 (48%) at local progression/recurrence following prior therapy (cohort B). In cohort A, most (n = 11) received concurrent IO. In cohort B, 3 recurred after surgery alone, 4 after systemic therapy alone and 4 after surgery and systemic therapy. RT consisted of 6 Gy x 6 (n = 11), 6 Gy x 5 (n = 10) and 5 Gy x 5-6 (n = 2) delivered to the primary tumor + 0.5 cm margin. Patients initiated IO either ≥3 months preRT (n = 8), concurrent with RT (n = 12) or ≥3 months following RT (n = 2). 1 patient in cohort B did not receive IO. Toxicity was graded using CTCAE v 5. Overall survival (OS) was measured from end of RT. Cumulative incidence of local progression was measured from end of RT. Kaplan-Meier method and Cox regression were used for survival analyses. Landmark method was used for timing of IO. Median follow-up as determined by reverse Kaplan-Meier method was 60 months (95% CI: 37-N/A). Overall incidence of acute/late grade 2+ toxicity for the entire cohort was 34%. Grade 2 acute toxicity included: dermatitis (n = 3), urinary (n = 2), vaginitis (n = 2) and diarrhea (n = 1). 3 patients experienced grade 3 acute dermatitis. 1 patient experienced late grade 2 vaginitis. No grade 3 or 4 toxicity was noted. No significant differences in toxicity were noted between RT regimens. Local disease control was achieved in 61% of patients. Local only, local and distant, and distant-only progression were seen in 17%, 22%, and 30% of patients respectively. 2-year cumulative incidence of local progression was 33% for the whole cohort, 28% for cohort A, and 36% for cohort B (p = 0.4). On UVA, factors associated with local progression were vulvar disease (p = 0.02) and c-KIT mutation (p = 0.011). No significant difference in local control was noted based on biologic effective dose (BED10 < = 48Gy vs >48Gy) (p = 0.06). Median OS for entire cohort, cohort A, and cohort B were 46, 72, and 30 months, respectively. 2-year survival (95% CI) was 67% (50%-91%), 73% (51%-100%), and 64% (41%-99%) respectively. On UVA, non-local disease at time of RT (p = 0.016) and receipt of IO ≥3 months prior to RT (p = 0.030) had worse OS. UH-RT+/- IO for melanoma of the LGT is well-tolerated with local disease control achieved in 61% of patients. Vulvar primary and c-Kit mutations were associated with worse local control. Additional follow-up may be necessary to determine the value of dose escalation.

Fractionated stereotactic radiotherapy of brain metastases: results of a retrospective study

BackgroundLasting local control of brain metastases following stereotactic radiotherapy is becoming increasingly relevant since systemic treatment constantly improves the prognosis of patients with extracranial metastases.Methods73 patients with 103 brain metastases received hypofractionated stereotactic radiotherapy (FSRT) in 6 fractions of 5 Gy between January 2017 and December 2021 at the University Hospital Regensburg, Germany. The study retrospectively evaluated local progression free survival (LPFS), overall survival (OS) and distant brain progression free survival (DPFS) of patients without prior radiotherapy of the brain. Response rate and brain radiation necrosis were reported. Cox proportional hazard models evaluated prognostic factors of OS and LPFS.ResultsThe median patient age was 61.0 years (Interquartile range, IQR 51.0, 67.5). The most common tumor types were malignant melanoma (34.2%) and non-small cell lung adenocarcinoma (26.0%). The median gross tumor volume (GTV) was 0.9 cm³ (IQR 0.4, 3.6). The median follow-up time of all patients was 36.3 months (95%CI 29.1, 43.4). The median OS was 17.4 months (95%CI 9.9, 24.9). Overall survival rates at 6-, 12-, 18-, 24-, and 30 months were 81.9%, 59.1%, 49.0%, 41.3%, and 37.2%, retrospectively. The mean LPFS was 38.1 months (95%CI 31.4, 44.9), while the median LPFS has not been reached. LPFS rates at 6-, 12-, 18-, 24- and 30 months were 78.9%, 68.7%, 64.3%, 61.6% and 58.7%, retrospectively. Median DPFS of all patients was 7.7 months (95%CI 6.1, 9.3). Six, 12-, 18-, 24- and 30 months DPFS rates were 62.1%, 36.3%, 31.1%, 24.8% and 21.7%. Five brain metastases (4.8%) developed brain radiation necrosis. In multivariate analysis, the number of brain metastases negatively affected LPFS. Non-melanoma and non-renal cell cancer was associated with a higher chance of LPFS in comparison to other cancer. A GTV > 1.5 cm³ translated into a higher risk of death compared to a GTV ≤ 1.5 cm³ and Karnofsky performance score was predictive of OS.ConclusionsFSRT in 6 fractions of 5 Gy seems to be an effective treatment with an acceptable local control for patients with brain metastases although melanoma and renal cell cancer seem to have a worse local control in comparison to other cancer.Trial registrationThis study is retrospectively registered.

4DCT is long overdue for improvement.

4DCT is long overdue for improvement.

Ten-year experience of bone SBRT in breast cancer: analysis of predictive factors of effectiveness.

Data on the benefit of stereotactic body radiation therapy (SBRT) in patients with breast cancer (BC) and bone metastases remain limited. The purpose of this study is to report our 10-year experience of bone SBRT, analyzing toxicity and prognostic factors for local control (LC); progression-free survival, and overall survival (OS). We analyzed all spine and non-spine bone SBRT performed in patients with BC during the 2012-2022 period at our institution. Treatments carried out with ablative intent in stereotactic conditions with dose/fraction ≥ 5Gy in 5 or fewer sessions were considered. Demographic, treatment, and toxicity data were recorded according to CTCAEv4. Risk factors were assessed through univariate and multivariate analysis by Cox regression. 60 bone SBRT treatments were performed during the study period. 75% were spine SBRT and 25% were non-spine SBRT (median BED4Gy was 80 Gy4). The median age was 52.5years (34-79). The median tumor volume was 2.9 cm3 (0.5-39.4). The median follow-up was 32.4months (1.2-101.7). 1 and 2years LC were 92.9 and 86.6%, respectively. 1 and 2years OS were 100 and 90.6%, respectively. Multivariate analysis (MVA) associated volume of the treated lesion ≥ 13 cm3 with worse LC (p = 0.046; HR 12.1, 95%CI = 1.1-140.3). In addition, deferring SBRT > 3months after lesion diagnosis to prioritize systemic treatment showed a significant benefit, improving the 2years LC up to 96.8% vs. 67.5% for SBRT performed before this period (p = 0.031; HR 0.1, 95%CI = 0.01-0.8). Hormonal receptors, the total number of metastases, and CA15-3 value were significantly associated with OS in MVA. During follow-up, three non-spine fractures (5%) were observed. According to our data, bone SBRT is a safe and effective technique for BC. Upfront systemic treatment before SBRT offers a benefit in LC. Therefore, SBRT should be considered after prior systemic treatment in this population.

Oncologic outcomes after MRI-assisted image-guided brachytherapy with hybrid interstitial and intra-cavitary applicators under moderate sedation for locally advanced cervix cancer.

To report outcomes of using image-guided hybrid intra-cavitary/interstitial applicators under moderate sedation for locally advanced cervical cancer patients in our institution. A total of 69 fractions of brachytherapy with hybrid applicators were performed in 33 patients from January 2017 to April 2021. All patients underwent MRI pelvis 1 week pre-brachytherapy to determine suitability for interstitial brachytherapy and pre-plan needle placement. All insertion of applicators were performed under moderate sedation with midazolam and/or fentanyl. Fifty-eight (84.1%) fractions were planned with CT alone. Clinical outcomes, dose volume parameters, and toxicities were analyzed. The median follow-up was 28 months. A total of 320 needles (median, 5 needles per fraction) were implanted, with a median insertion depth of 3 cm (range, 1.5-4 cm). The median high-risk clinical target volume (HR-CTV) during initial brachytherapy was 34.5 cc (range, 17.8-74.7 cc). The median total EQD2 D2cc of the rectum, bladder, sigmoid, and small intestine colon was 71.8 Gy, 81.5 Gy, 69 Gy, and 58.3 Gy, respectively. The 2-year local control and overall survival were 80.7% and 77.7%, respectively. Larger volume HR-CTV was significantly associated with worse local control (HR = 1.08, p = 0.005) and overall survival (HR = 1.04, p = 0.015). None of the patients required in-patient admission or blood transfusion post-procedure. Late grade 3 gastrointestinal and genitourinary toxicities were observed in 4 patients (12.2%). Hybrid applicators inserted under moderate sedation are feasible and safe. Image-guided interstitial brachytherapy with CT planning aided by MRI performed 1 week pre-brachytherapy is associated with favorable outcomes and modest toxicities.

GSOR23 Presentation Time: 12:20 PM: Clinical Outcomes of Interstitial High-Dose Rate Brachytherapy with and without Concurrent Interstitial Hyperthermia for Gynecologic Malignancies

<h3>Purpose</h3> Radiosensitization with external hyperthermia (HT) has demonstrated improved oncologic outcomes for patients with gynecological (GYN) malignancies. However, similar data for multicatheter interstitial HT (IHT) with interstitial high-dose rate (IHDR) brachytherapy is limited. We present a single-institution experience of patients with GYN cancers treated using IHDR with and without concurrent IHT (IHDR-IHT). <h3>Materials and Methods</h3> We retrospectively analyzed 63 patients with locally advanced GYN malignancies treated with IHDR using a Syed-Neblett template (IHDR: 29 and IHDR-IHT: 34 patients). Primary indication for adding IHT was bulky, residual or recurrent disease guided by number, location and geometry of needle placement within HRCTV to allow placement of IHT antennae and thermistors. IHT (target temperature 40-44°C) was performed after IHDR treatment using the same set of interstitial catheters. The median age was 60 yrs (27- 89). Primary sites included cervical (n=40), endometrial (n=9), vaginal (n=10), vulvar (n=3), and non-GYN malignancy with vaginal invasion (n=1). Pelvic radiation therapy was performed prior to IHDR in all but one patient with median dose of 45 Gy (Range, 30.6-55.0 Gy) and 52 patients received concurrent chemotherapy. Median IHDR dose was 23.75 Gy (10-30.0) and number of fractions was 5 (2-5). IHDR and IHDR-IHT groups had similar proportion of reirradiation (p=0.55), stage ≥ III (p=0.11) and HRCTV volume (p=0.65) with marginally higher recurrent cases in the IHDR cohort (p=0.07). Median D90 HRCTV EQD2 was higher in IHDR-IHT (78.2 Gy; 14-105) vs IHDR group (75.9 Gy; range 61-86); p = 0.005. Respective median HRCTV volume were 61.3 cc (25-376) and 48.6 cc (12-175); p = 0.21. Chi -square and Mann-Whitney tests were done to compare variables between the two cohorts. The Kaplan-Meier method with Cox Regression was used to estimate overall survival (OS), local control (LC), locoregional control (LRC) and distant control (DC) and evaluate predictors of LC. <h3>Results</h3> IHDR-IHT and IHDR were well tolerated with no acute procedure-related adverse events. With a median follow up of 12.1 months (<1-59) in IHDR group and 11.0 months (1-76), 1 IHDR-HT patient developed acute CTCAE grade 3+ toxicity (grade 3 urinary obstruction in a patient with horseshoe kidney). Late Grade 3+ toxicity was seen in 9 patients (IHDR: 5, IHDR-IHT: 4 patients); ureteral stricture/incontinence (4), fistula (3) and radiation proctitis (2). Median OS was 31 versus 42 months (p=0.55) in the IHDR and IHDR-IHT groups, respectively. 1 yr LC for IHDR vs IHDR-IHT of 86.9% vs 77.8% (p=0.051). Corresponding, 1-yr LRC and DC were 82.5 vs 74.8% (p=0.056) and 81 vs 77.6% (p=0.84), respectively. On cox regression undergoing IHT (HR 4.7 [95% CI 1.3-16.9] p=0.02) was associated with worse local control. <h3>Conclusions</h3> To our knowledge, this is the largest report describing outcomes from the addition of IHT to IHDR in patients with locally advanced GYN malignancies. Use of IHT had excellent tolerance without any procedural complications. With possible group imbalances, trend to shorter LC and LRC was seen in IHT. Prospective controlled studies will be needed to evaluate clinical benefits.

Mature Local Control and Radiation Necroses Outcomes Specific to Brain Metastases Treated with Salvage Stereotactic Radiosurgery for Radiosurgical Failures

<h3>Purpose/Objective(s)</h3> The management of locally recurrent brain metastases is a clinical challenge. A second course of radiosurgery may be delivered as the primary salvage treatment or as postoperative radiosurgery to the surgical cavity if the recurrence resected. We report our institutional experience of repeat radiosurgery for locally recurrent brain metastases, with a focus on local control and radionecrosis (RN) outcomes. <h3>Materials/Methods</h3> We report a single institution retrospective cohort study specific to patients with recurrent brain metastases treated with repeat radiosurgery. Clinical and dosimetric details were collected. Overall survival was estimated using the Kaplan Meier method. Local recurrence and RN rates were estimated using the Aalen-Johnson method, with death from any cause as the competing risk for both endpoints. Univariable competing risk regression using Fine and Gray's methods were performed, and subsequent multivariable (MVA) regression based on a priori variable selection generated final adjusted models. <h3>Results</h3> We identified 96 patients and 130 brain metastases re-treated with radiosurgery (either single fraction or hypofractionation between July 2010 to April 2020. The most common primary sites were lung (N = 44, 33.8%), breast, (N = 38, 29.2%), and melanoma (N = 26, 20%). More than half of the retreated lesions were postoperative cavities (N = 68, 52.3%). Re-treatment was most commonly delivered with 25 Gy in 5 fractions (N = 77, 59.2%) followed by 27.5 Gy in 5 fractions (N = 23, 17.7%). The mean BED₁₀ was 39.71 Gy (standard deviation [SD] 6.16) with a mean treatment volume of 14.94 cm³ (SD, 20.15). Nearly half (N = 64, 49.2%) of lesions were treated in the absence of systemic therapy, while 43.8% (N = 57) and 6.9% (N = 9) were treated while receiving targeted therapy/immunotherapy and chemotherapy, respectively. The median time between treatment courses was 13.7 months (IQR 10.88). With a median follow up of 34.9 months (interquartile range [IQR] 25-41.9), the 1 and 2-year overall survival rates were 59.8% (95% confidence interval [95% CI] 50.4-70.9) and 36.2% (95% CI, 27.2-48.2), respectively. The risk of local failure at 1 and 2 years was 26.2% (95%CI, 18.5-34) and 28% (95%CI, 20.1-35.9), respectively. MVA identified increasing target volume (hazard ratio [HR] 1.03; 95% CI, 1.02-1.04), and a shorter time-interval between radiosurgery courses (HR 0.29; 95% CI, 0.19-0.45) to be associated with worse local control. The crude incidence of RN was 18.5% (N = 24), of which 8 events (6.15%) were symptomatic. The 1 and 2-year rates of RN were 17.6% (95% CI, 10.9-34) and 19.3% (95%CI, 12.3-35.9), respectively. <h3>Conclusion</h3> Repeat radiosurgery for locally recurrent brain metastases results in good local control with a moderate risk of RN. Larger target volume and a shorter timeframe between radiosurgery treatments are associated with worse control.

Outcomes of radiation-induced meningiomas treated with stereotactic radiosurgery.

Data on the efficacy and safety of stereotactic radiosurgery (SRS) for treatment of radiation-induced meningiomas (RIMs) are limited. A single institution database of Cobalt-60 SRS cases from 08/1999 to 10/2020 was reviewed. Radiation-induced meningiomas were identified using Cahan's criteria. Endpoints included overall survival (OS), progression free survival (PFS), local control (LC), treatment failure, and treatment toxicity. Univariate and multivariate analyses were performed using cox proportional hazard models. A total of 29 patients with 86 RIM lesions wereidentified. Median follow-up after SRS was 59months. The median dose prescribed to the 50% isodose line was 14Gy (range 12-20Gy). The actuarial 5-yr OS and PFS were 96% and 68%, respectively. Patients treated for recurrent RIMs had a significantly lower PFS (45% vs 94% at 3yr, p < 0.005) than patients treated in the upfront setting. Patients with presumed or WHO grade I RIMs had a significantly greater PFS (3-year PFS 96% vs 20%) than patients with WHO grade II RIMs (p < 0.005). On a per-lesion basis, local control (LC) at 1-, 3-, and 5-yrs was 82%, 76%, 74%, respectively. On multivariate analysis, female gender was associated with improved LC (p < 0.001), while marginal doses > 14Gy were associated with worse local control (p < 0.001). Grade I-III toxicity following treatment was 9.0%. Stereotactic radiosurgery is a safe and effective treatment option for radiographic RIMs, WHO grade I RIMs, or lesions treated in the upfront setting. WHO grade II lesions and recurrent lesions are at increased risk for disease progression.

31412 Response and local control in patients treated with low-dose radiotherapy for tumoral mycosis fungoides

Background: Mycosis fungoides (MF) is often characterized by patches or plaques that may progress into tumoral lesions (TLs). Low-dose radiotherapy (LDRT) is an effective option for local palliation, but little evidence exists regarding its efficacy for TLs. Methods: 73 lesions in 18 patients treated with LDRT (8 Gy in 2 fractions) for MF between 2013-2020 were analyzed. Response was determined at first follow-up and defined as: complete response (CR),; partial response (PR), ≥50% reduction; no response (NR), <50% reduction. Results: Median age was 68 years and 64% of lesions were on the extremities. 25 lesions were tumoral and 48 were nontumoral. A greater proportion of African American individuals were observed in the TL group (52% v. 25%). Five lesions (all TL) had biopsy-confirmed large cell transformation. Median follow-up was 9.3 months. Overall CR/PR rate was 93.2% (97.9% nonTL v. 84% TL, P = .04). In the non-TL versus TL groups, CR was observed in 16.7% v. 4.0%, PR in 81.2% v. 80.0%, NR in 2.1% v. 16.0%, respectively. Local progression occurred in 6/25 TL and 0/48 non-TL. Local control at 6-, 12-, and 24-months was 100% for non-TLs compared with 86.6%, 80.8%, and 60.6% for TLs (P < .01). Median time-to-progression was 5.5 months. Conclusion: LDRT offers clinically meaningful response and durability of palliation in most patients with tumoral MF, despite lower response rates and worse local control. This may represent a reasonable option for palliation of tumoral lesions for patients in whom the risk/benefit profile is acceptable.

Treatment Outcomes of Computer Tomography-Guided Brachytherapy in Cervical Cancer in Hong Kong: A Retrospective Review.

Simple SummaryThis retrospective study reviews 135 patients with locally advanced cervical cancer treated with chemo-radiotherapy with image-guided adaptive brachytherapy with CT guidance. The study has a long follow-up period of 53.6 months. The outcome was excellent with a five-year local control, pelvic control, distant metastasis-free survival and overall survival rates being 90.7%, 84.2%, 80.0% and 87.2%, respectively. Adenocarcinoma was significantly associated with worse local control, pelvic control, distant metastasis-free survival and overall survival rates.(1) Background: To report the long-term clinical outcomes of computer-tomography (CT)-guided brachytherapy (BT) for locally advanced cervical cancer. (2) Methods: A total of 135 patients with FIGO stage IB-IVA cervical cancer treated with definitive radiotherapy +/− chemotherapy with an IGABT boost at Queen Mary Hospital, Hong Kong, between November 2013 and December 2019 were included. Treatment included pelvic radiotherapy 40 Gy/20 Fr/4 weeks +/− chemotherapy then CT-guided BT (7 Gy × 4 Fr) and a sequential parametrial boost. The primary outcome was local control. Secondary outcomes were pelvic control, distant metastasis-free survival, overall survival (OS) and late toxicities. (3) Results: The median follow-up was 53.6 months (3.0–99.6 months). The five-year local control, pelvic control, distant metastasis-free survival and OS rates were 90.7%, 84.3%, 80.0% and 87.2%, respectively. The incidence of G3/4 long-term toxicities was 6.7%, including proctitis (2.2%), radiation cystitis (1.5%), bowel perforation (0.7%), ureteric stricture (0.7%) and vaginal stenosis and fistula (0.7%). Patients with adenocarcinomas had worse local control (HR 5.82, 95% CI 1.84–18.34, p = 0.003), pelvic control (HR 4.41, 95% CI 1.83–10.60, p = 0.001), distant metastasis-free survival (HR 2.83, 95% CI 1.17–6.84, p = 0.021) and OS (HR 4.38, 95% CI: 1.52–12.67, p = 0.003) rates. Distant metastasis-free survival was associated with HR-CTV volume ≥ 30 cm3 (HR 3.44, 95% CI 1.18–9.42, p = 0.025) and the presence of pelvic lymph node (HR 3.44, 95% CI 1.18–9.42, p = 0.025). OS was better in patients with concurrent chemotherapy (HR 4.33, 95% CI: 1.40–13.33, p = 0.011). (4) Conclusions: CT-guided BT for cervical cancer achieved excellent long-term local control and OS. Adenocarcinoma was associated with worse clinical outcomes. (4) Conclusion: CT-guided BT for cervical cancer achieved excellent long-term local control and OS. Adenocarcinoma was associated with worse clinical outcomes.

Surgical margins after neoadjuvant chemoradiotherapy for locally advanced vulvar carcinoma: What is an adequate margin? (531)

Surgical margins after neoadjuvant chemoradiotherapy for locally advanced vulvar carcinoma: What is an adequate margin? (531)

Bladder-sparing (chemo)radiotherapy in elderly patients with muscle-invasive bladder cancer: a retrospective cohort study

Background Organ-sparing treatment for muscle-invasive bladder cancer by maximal transurethral removal of the tumor (TURB) followed by chemoradiation (CRT) has shown promising results in recent studies, and is therefore considered to be an acceptable alternative for the standard of radical cystectomy (RC) in selected patients. We report on outcomes in a single-center, retrospective CRT cohort in comparison to a RC and radiotherapy only (RT) cohort. Patients and methods The patient population included n = 84 CRT patients, n = 93 RC patients, and n = 95 RT patients. Primary endpoints were local control (LC) up to 2 years and overall survival (OS) up to 5 years. Cox regression was performed to determine risk factors for LC and OS in the CRT group. Acute genito-urinary (GU) and gastro-intestinal (GI) toxicity were scored with CTCAE version 4 for the RT and CRT cohort. Logistic regression was used to determine risk factors for toxicity. We followed the EQUATOR guidelines for reporting, using the STROBE checklist for observational research. Results Baseline characteristics were different between the treatment groups with in particular worse comorbidity scores and higher age in the RT cohort. The CRT schedule was completed by 96% of the patients. LC at 2 years was 83.4% (90% CI 76.0–90.8) for CRT vs. 70.9% (62.2–79.6) for RC and 67.0% (56.8–77.2) for RT. OS at 5 years was 48.9% (38.4–59.4) for CRT vs. 46.6% (36.4–56.8) for RC, and 27.6% (19.4–35.8) for RT. High T stage was significantly associated with worse LC and OS in the CRT group. GU/GI toxicity grade ≥2 occurred in 43 (48.3%) RT patients and 38 (45.2%) CRT patients. Conclusions The organ-preserving strategy with CRT was feasible and tolerable in this patient population, and the achieved LC and OS were satisfactory in comparison to the RC cohort and literature.

Progression-Free Survival and Local Control After SABR for up to 5 Oligometastases: An Analysis From the Population-Based Phase 2 SABR-5 Trial

Despite increasing utilization of SABR for oligometastatic cancer, prospective outcomes are lacking. The purpose of this study was to determine progression-free survival (PFS), local control (LC), and prognostic factors from the population-based phase 2 SABR-5 trial. The SABR-5 trial was a single-arm phase 2 study with the primary endpoint of toxicity, conducted at the 6 regional cancer centers across British Columbia (BC), Canada, during which time SABR for oligometastases was only offered on trial. Patients with up to 5 oligometastases (total or not controlled by prior treatment and including induced oligometastatic disease) underwent SABR to all lesions. Patients were 18 years of age or older, had an Eastern Cooperative Oncology Group score of 0 to 2, and had life expectancy ≥ 6 months. The secondary outcomes of PFS and LC are presented here. Between November 2016 and July 2020, 381 patients underwent SABR on trial. Median follow-up was 27 months (interquartile range, 18-36). Median PFS was 15 months (95% confidence interval [CI], 12-18). LC at 1 and 3 years were 93% (95% CI, 91-95) and 87% (95% CI, 84-90), respectively. On multivariable analysis, increasing tumor diameter (hazard ratio [HR], 1.09; P < .001), declining performance status (HR, 2.13; P < .001), disease-free interval <18 months (HR, 1.52; P=.003), 4 or more metastases at SABR (HR, 1.48; P=.048), initiation or change in systemic treatment (HR, 0.50; P < .001), and oligoprogression (HR, 1.56; P=.008) were significant independent predictors of PFS. Tumor diameter (sub-hazard ratio [SHR], 1.28; P < .001), colorectal histology (SHR, 4.33; P=.002), and "other" histology (SHR, 3.90; P < .001) were associated with worse LC. In this population-based cohort including patients with genuine oligometastatic, oligoprogressive, and induced oligometastatic disease, the median PFS was 15 months and LC at 3 years was 87%. This supports ongoing efforts to randomize patients in phase 3 trials, even outside the original 1 to 5 metachronous oligometastatic paradigm.

Correlation and colocalization of HIF-1α and pimonidazole staining for hypoxia in laryngeal squamous cell carcinomas: A digital, single-cell-based analysis

ObjectiveTumor hypoxia results in worse local control and patient survival. We performed a digital, single-cell-based analysis to compare two biomarkers for hypoxia (hypoxia-inducible factor 1-alpha [HIF-1α] and pimonidazole [PIMO]) and their effect on outcome in laryngeal cancer patients treated with accelerated radiotherapy with or without carbogen breathing and nicotinamide (AR versus ARCON). Materials and MethodsImmunohistochemical staining was performed for HIF-1α and PIMO in consecutive sections of 44 laryngeal cancer patients randomized between AR and ARCON. HIF-1α expression and PIMO-binding were correlated using digital image analysis in QuPath. High-density areas for each biomarker were automatically annotated and staining overlap was analyzed. Kaplan-Meier survival analyses for local control, regional control and disease-free survival were performed to predict a response benefit of ARCON over AR alone for each biomarker. Results106 Tissue fragments of 44 patients were analyzed. A weak, significant positive correlation was observed between HIF-1α and PIMO positivity on fragment level, but not on patient level. A moderate strength correlation (r = 0.705, p < 0.001) was observed between the number of high-density staining areas for both biomarkers. Staining overlap was poor. HIF-1α expression, PIMO-binding or a combination could not predict a response benefit of ARCON over AR. ConclusionDigital image analysis to compare positive cell fractions and staining overlap between two hypoxia biomarkers using open-source software is feasible. Our results highlight that there are distinct differences between HIF-1α and PIMO as hypoxia biomarkers and therefore suggest co-existence of different forms of hypoxia within a single tumor.