Actuarial Local Control Research Articles

Supracricoid Partial Laryngectomy Versus Radiation Therapy for cT3N0M0 Glottic SCC: Outcomes in Candidates for Total Laryngectomy Responding Well to Induction Chemotherapy.

To evaluate whether supracricoid partial laryngectomy (SCPL) may be a viable alternative to radiation therapy (RT) for patients with glottic cT3N0M0 squamous cell carcinoma (SCC) who are surgical candidates for total laryngectomy (TL) and respond well to platinum-based induction chemotherapy. Retrospective case series review of 18 consecutive patients with cT3N0M0 glottic SCC, initially considered surgical candidates only for TL who showed a good response to platinum-based induction chemotherapy, managed at a French university teaching institution with either SCPL (n = 9) or RT (n = 9). The main endpoints were 10-year local control and laryngeal preservation. The secondary endpoints were 10-year survival, causes of death analysis, and univariate analysis of local control and survival. The 10-year actuarial local control, laryngeal preservation, survival rates were 77.8%, 88.9%, and 66.7% after SCPL, respectively, and 72.9%, 87.5%, and 33.3%, after RT without significant statistical differences. In univariate analysis none of the clinical variables under analysis were related to local control and survival. Our data suggest that SCPL may warrant further consideration as a treatment option for glottic cT3N0M0 SCC patients who respond well to platinum-based induction chemotherapy. However, additional prospective research is warranted given the retrospective, nonrandomized nature of the presented case series.

Multi-institutional study using sbrt to treat mediastinal and hilar lymphadenopathy.

Mediastinal and hilar lymphadenopathy (MHL) is a common pattern of cancer spread, particularly in lung disease. Recently, there has been interest in the use of SBRT for MHL, especially in the oligometastatic setting. The goal is to improve local control (LC) and to achieve shorter treatment durations to minimize systemic treatment interruptions. The primary endpoint of this study was local control (LC). The secondary endpoints were distant metastasis-free survival (DMFS), progression-free survival (PFS), and overall survival (OS) and predictive factors of response. This is a retrospective study. It analyses a group of patients treated with SBRT for MHL with different primary tumours and histologies. From November 2007 to June 2023, we treated 159 MHL in 128 patients. The primary most represented was lung cancer. A single fraction was used in 16% of cases and multiple fractions in 84% of cases. The medium BED 10 was 75.06Gy (range: 37-120Gy). Actuarial LC rates at 1, 2 and 5 years were 80.0%, 78.8% and 75.2%. The actuarial DMFS rates at 1, 2 and 5 years were 43.9%, 34.1% and 14.1%, respectively. Actuarial PFS rates at 1, 2 and 5 years were 37.2%, 23.9% and 8.3%, respectively. Actuarial OS rates at 1, 2 and 5 years were 68.8%, 52.7% and 26.9%, respectively. SBRT may be an option for the treatment of MHL. In addition, achieving a complete response is one of the most important predictors of our endpoints, in addition to tumour burden and volume.

Investigating the Local Effectiveness of Carbon Ion Radiotherapy for Unresectable Female Genital Tract Melanomas: A Preliminary Real-World Study.

Background/Objectives: Primary gynecological melanomas are rare malignancies with lower survival rates compared to cutaneous melanomas. Both preclinical and clinical data support the evidence that mucosal melanomas are photon-radioresistant but responsive to carbon ion radiotherapy (CIRT). The aim of this study is to assess, in a real-world cohort, the effectiveness and tolerability of radical CIRT in patients with inoperable gynecological mucosal melanoma. Methods: This is a real-world study aimed to assess the effectiveness and the safety of CIRT in this setting. We defined as the primary endpoints the objective response rate (ORR) and the clinical benefit (CB). The secondary endpoints included the actuarial local control rate (LC) assessed after 1 year and 2 years and the toxicity scored according to CTCAE v.5. Actuarial outcomes were analyzed using the Kaplan-Meier method, while potential predictors were investigated through the Log-rank test. Results: Between 2017 and 2023, eleven Caucasian patients underwent pelvic CIRT (total dose 68.8 GyRBE) for mucosal malignant melanoma of the vulva or the vagina. With a median follow-up of 18 months, we observed an ORR of 82% and a CB of 100%. LC at 1 and 2 years was 100% and 86%, respectively, and among the factors analyzed for their potential impact on LC, age < 60 years seems to be a potential predictor (p = 0.014). The treatment was well tolerated, with only one case of acute grade 3 erythema and, in the late phase, one case of grade 3 erythema and grade 3 urethral toxicity. Conclusions: CIRT was effective and safe for gynecological melanomas. Larger collaborative cohort studies and longer follow-ups are needed to take a step forward in comprehending the correct management of this disease.

Definitive Radiotherapy for Oligometastatic and Oligoprogressive Thyroid Cancer: A Potential Strategy for Systemic Therapy Deferral.

Definitive radiotherapy (dRT) has been shown to be an effective option for patients with oligometastatic and oligoprogressive cancers; however, this approach has not been well-studied in metastatic thyroid cancer. This retrospective cohort included 119 patients with oligometastatic (34%) and oligoprogressive (66%) metastatic thyroid cancer treated from 2005 to 2024 with 207 dRT courses for 344 sites (50% thoracic, 37% bone, 7.5% brain, 4% abdominopelvic, and 1.5% neck/skull base). Histologies included 61% papillary, 15% poorly differentiated, 13% follicular, and 10% oncocytic, and 114 (96%) patients had radioiodine-refractory disease prior to dRT. Each course involved 1 to 5 sites, with prescriptions intended for definitive control (median BED10, 72 Gy), and palliative RT was excluded. Somatic mutation testing for oncologic drivers was performed in 103 (87%) patients. Each patient had an average of 3 sites (range, 1-23) treated over 2 courses (range, 1-9). Follow-up from first dRT was a median 2.5 years, with overall survival at 3 and 5 years of 81.5% and 70%, respectively. Actuarial local control per site was 91% at 3 years. Median progression-free survival (PFS) after first course was 17 months (95% CI, 10-24 months), with poorly differentiated histology associated with worse outcomes (hazard ratio [HR], 2.20; 95% CI, 1.24-3.90; P=.007), BRAF mutation with improved PFS (HR, 0.59; 95% CI, 0.37-0.95; P=.029), and no significant findings with respect to systemic therapy. At initial dRT, 92 (77%) patients were not on systemic therapy; and after first dRT, freedom from systemic therapy escalation was a median 4.1 years (95% CI, 1.7-6.5 years), with 2- and 5-year continued deferral rates of 73% and 46%, respectively. Grade 3 toxicities were noted for 1.5% of courses, with no grade 4-5 events observed. This study underscores the potential of dRT as a feasible strategy for deferring systemic therapy escalation in patients with oligometastatic and oligoprogressive metastatic thyroid cancer, demonstrating that sequential dRT courses impart excellent local control and are safe to deliver repeatedly for multiple distant sites. Further studies are warranted to validate these findings and elucidate the full benefit of dRT as part of a multidisciplinary approach for metastatic thyroid cancer.

Ten-Year Outcome After Supracricoid Partial Laryngectomy in cT3M0 Laryngeal Squamous Cell Carcinoma-A STROBE Analysis.

The aim of this study was to document 10-year outcomes after supracricoid partial laryngectomy (SCPL) in selected cT3M0 laryngeal squamous cell carcinoma (SCC) patients. This real-life retrospective observational study analyzed an inception cohort of 168 patients with isolated, untreated, selected cT3M0 laryngeal SCC, that were consecutively managed by SCPL during the period 1973-2013, and followed up until death or for a minimum of 10 years in 92% of cases at a single French academic and tertiary referral care center. Prior induction chemotherapy, arytenoid cartilage removal, level II-IV neck dissection, and postoperative radiation therapy were performed on 148, 77, 136, and 27 patients, respectively. The main objective was to determine 10-year actuarial local control and laryngeal preservation estimates. Secondary objectives included 10-year actuarial survival and cause-of-death analysis, and assessment of correlations between endpoints and clinical variables. The significance threshold was set at p < 0.005. Ten-year actuarial local control, laryngeal preservation, and survival estimates were 90%, 85%, and 52%, respectively. Salvage treatment resulted in an overall 99% local control rate. Metachronous second primary cancer, intercurrent disease without evidence of SCC, SCPL-related death, and uncontrolled local recurrence accounted for 31%, 26%, 7%, and 2% of causes of death. On univariate analysis, overall local recurrence and laryngeal preservation rates varied significantly, from 5% to 54% and 90% to 46% when resection margins were R0 and R1, respectively. The present study highlighted successful 10-year outcomes after SCPL, providing further evidence in favor of its integration into the conservative armamentarium for endolaryngeal cT3 SCC. 4 Laryngoscope, 134:4557-4563, 2024.

Contact X-ray Brachytherapy as a sole treatment in selected patients with early rectal cancer – Multi-centre study

Background and purposeRadical surgery is the standard of care for early rectal cancer. However, alternative organ-preserving approaches are attractive, especially in frail or elderly patients as these avoid surgical complications. We have assessed the efficacy of sole Contact X-ray Brachytherapy (CXB) treatment in stage-1 rectal cancer patients who were unsuitable for or declined surgery. Materials and methodsThis retrospective multi-centre study (2009–2021) evaluated 76 patients with T1/2-N0-M0 rectal adenocarcinomas who were treated with CXB alone. Outcomes were assessed for the entire cohort and sub-groups based on the T-stage and the criteria for receiving CXB alone; Group A: patients who were fit enough for surgery but declined, Group B: patients who were high-risk for surgery and Group C: patients who had received prior pelvic radiation for a different cancer. ResultsWith a median follow-up of 26(IQR:12–49) months, initial clinical Complete Response (cCR) was 82(70–93)% with rates of local regrowth 18(8–29)%, 3-year actuarial local control (LC) 84(75–95)%, distant relapse 3 %, and no nodal relapse. 5-year disease-free survival (DFS) and overall survival (OS) were 66(48–78)% and 58(44–75)%. Lower OS was observed in Groups B [HR:2.54(95 %CI:1.17, 5.59), p = 0.02] and C [HR:2.75(95 %CI:1.15, 6.58), p = 0.03]. Previous pelvic radiation predicted lower cCR and OS. The main toxicity was G1-2 rectal bleeding (26 %) and symptoms of impaired anal sphincter function were not reported in any patients. ConclusionCXB treatment alone achieved a high cCR rate with satisfactory LC and DFS. Inferior oncological outcomes were observed in patients who had received prior pelvic radiotherapy. CXB alone, with its favourable toxicity profile and avoidance of general anaesthesia and surgery risks, therefore, can be considered for patients who are unsuitable for or refuse surgery.

Stereotactic Body Radiation Therapy for Oligoprogressive Ovarian Cancer Patients Treated During Poly(ADP‐Ribose)‐Polymerase Inhibitor Maintenance: Efficacy and Adverse Events From the Epimetheo Retrospective Study

The aim of this observational, retrospective, multicenter study (Epimetheo) was to analyze the activity and the safety of stereotactic body radiation therapy (SBRT) during poly(ADP-ribose)-polymerase inhibitor (PARPi) maintenance in a series of oligometastatic ovarian cancer (OC) patients. Patients treated with PARPi in maintenance setting received SBRT if oligometastatic progression occurred. Maintenance treatment was continued until the extensive progression of the disease. The primary endpoints of the study were as follows: next systemic treatment change-free survival (NEST-FS) and acute and late toxicity; the secondary endpoints were as follows: the rate of clinical complete response (CR), the 2-year actuarial local control (LC, progression of disease inside SBRT field) rate on "per lesion" basis, the 2-year actuarial progression-free survival, and 2-year overall survival (OS). From April 2018 to September 2023, SBRT was used to treat 74 OC patients with a total of 158 lesions (98 lymph nodes and 60 parenchymal lesions) under PARPi maintenance. Olaparib, niraparib, and rucaparib were administered to 41.9%, 48.6%, and 9.5% of patients, respectively. CR, partial response, stable disease, and progressive disease were observed in 115 (72.8%), 32 (20.3%), 9 (5.7%), and 2 lesions (1.3%), respectively. Severe toxicities were reported in less than 3% of patients. The actuarial median NEST-FS was 10 months, with a range of 6.7-13.3 months. The 12- and 24-month actuarial NEST-FS rates were 44.9% and 31.4%, respectively. The 2-year actuarial LC, progression-free survival, and OS were 68.1%, 22.5%, and 77%, respectively with differences in figures between complete and incomplete responders. The achievement of CR was found to be correlated with an improvement in LC and OS. This study reports the activity and the low toxicity profile of SBRT in association with PARPi in oligometastatic OC patients. A rapid, minimally invasive, and cost-effective treatment such as SBRT may be proposed as a means of prolonging NEST-FS and maintaining an effective treatment regimen involving PARPi.

Stereotactic radiotherapy for liver oligometastases: a pooled analysis following the estro/eortc consensus recommendations.

A large pooled analysis of liver oligometastases, classified accordingly to the ESTRO/EORTC recommendations, treated by stereotactic radiotherapy (SBRT) and Radiosurgery (SRS) was carried out. The clinical and dosimetric data of patients who underwent SBRT/SRS for liver metastases were analysed in terms of efficacy and toxicity profile. In particular, the Local Control (LC), the Distant Metastases Free Survival (DMFS), the Disease-Free Survival (DFS), the Overall Survival (OS), and the Next Systemic Therapy Free Survival (NEST-FS) rates were analysed. 113 patients (M/F: 49/64), accounting for a total of 150 hepatic lesions (March 2006-February 2023) in two Italian radiotherapy Institutions were evaluated. Median age was 67years old (36-92) and 48 (42.5%) patients had at least one comorbidity. The majority of the lesions were induced (30.7%) or repeated oligoprogressive (12.7%) metastases. 98 lesions were treated with more than one daily fraction (mainly 50Gy in 5 fractions), while 52 were radiosurgery treatments (mainly 32Gy). The treatment response at 3-4months was evaluable in 147 lesions: complete response was 32.0%, partial response 17.0%, and stable disease 32.0%. Actuarial LC, DMFS, DFS, OS, and NEST-FS at 1 year were 75.8%, 37.7%, 34.9%, 78.7%, and 59.4% respectively; while actuarial LC, DMFS, DFS, OS, and NEST-FS at 2 years were 52.1%, 24.9%, 21.9%, 51.3%, and 36.8%, respectively. The achievement of complete response, synchronous oligometastases, and no treatment interruptions correlated with a more favorable outcomes. As per the toxicity profile, we registered only two acute and one late toxicity cases higher than grade 2. Stereotactic treatment for liver metastases seems to be a safe and promising option in terms of local control. The best results in term of outcomes have been obtained in patients with complete response, synchronous oligometastases, favorable histology, and no treatment interruptions.

The first real-world study on the role of carbon ion radiotherapy for oligo-metastatic, persistent, or recurrent (MPR) ovarian/fallopian tube cancer

IntroductionIn the multidisciplinary management of oligometastatic, persistent, or recurrent (MPR) ovarian cancer, radiotherapy (RT) is becoming a more and more worthwhile treatment to potentially improve the chronicity of the disease. Particle beam RT has proved to be effective in several gynecological malignancies, but so far no data are available for ovarian cancer. Material and MethodsThis is a real-world, retrospective, bi-institutional, single-arm study aimed to assess the effectiveness and the safety of carbon ion RT (CIRT) in this setting. The co-first endpoints are 1-year and 2-year actuarial local control (LC) rates and the objective response rate (ORR) defined on a “per lesion” basis. The secondary endpoint was toxicity. Actuarial outcomes were evaluated using the Kaplan-Meier method while potential predictors were explored using the Log-rank test. Bi-variable logistic regression was employed in the analysis of factors predicting the complete response on a per-lesion basis. Results26 patients accounting for a total of 36 lesions underwent CIRT with a total median dose of 52.8 Gy[RBE] (range: 39–64 Gy[RBE]). Five patients received CIRT for re-irradiation. No concomitant systemic therapies were administered during CIRT. Within 12 months after the treatment, 17 lesions (47 %) achieved complete response while 18 (50 %) obtained a partial response with an ORR of 97 %. The achievement of a complete response is related to the dose per fraction (>4.2 Gy[RBE], p = 0.04) and total dose (>52,8 Gy[RBE], p = 0.05). The 1-year LC was 92 % and the 2-year LC was 83 %, according to the achievement of a CR (p = 0.007) and GTV ≤ 14 cm3 (p = 0.024). No grade > 3 toxicities were recorded both in naïve and re-irradiated patients. PARP-i and anti-VEGF seemed not to exacerbate the risk of severe toxicities. ConclusionsCIRT was effective and safe in MPR ovarian cancers, even in the case of re-irradiation. Largest cohort studies and longer follow-up are needed to confirm these data.

SBRT-SG-01: final results of a prospective multicenter study on stereotactic body radiotherapy for liver metastases.

This study aimed to assess the efficacy and tolerability of stereotactic body radiation therapy (SBRT) for the treatment of liver metastases. Patients with up to 5 liver metastases were enrolled in this prospective multicenter study and underwent SBRT. Efficacy outcomes included in-field local control (LC), progression-free survival (PFS), and overall survival (OS). Acute and late toxicities were evaluated using CTCAE v.4.0. A total of 52 patients with 105 liver metastases were treated between 2015 and 2018. The most common primary tumor was colorectal cancer (72% of cases). Liver metastases were synchronous with the primary tumor diagnosis in 24 patients (46.2%), and 21 patients (40.4%) presented with other extrahepatic oligometastases. All patients underwent intensity-modulated radiation therapy (IMRT)/volumetric-modulated arc therapy (VMAT) with image-guided radiation therapy (IGRT) and respiratory gating, and a minimum biologically effective dose (BED10Gy) of 100Gy was delivered to all lesions. With a median follow-up of 23.1months (range: 13.4-30.9months) since liver SBRT, the median actuarial local progression-free survival (local-PFS) was not reached. The actuarial in-field LC rates were 84.9% and 78.4% at 24 and 48months, respectively. The median actuarial liver-PFS and distant-PFS were 11 and 10.8months, respectively. The actuarial median overall survival (OS) was 27.7months from SBRT and 52.5months from metastases diagnosis. Patients with lesion diameter ≤ 5cm had significantly better median liver-PFS (p = 0.006) and OS (p = 0.018). No acute or late toxicities of grade ≥ 3 were observed. This prospective multicenter study confirms that liver SBRT is an effective alternative for the treatment of liver metastases, demonstrating high rates of local control and survival while maintaining a low toxicity profile.

Definitive single fraction spine stereotactic radiosurgery for metastatic sarcoma: Simultaneous integrated boost is associated with high tumor control and low vertebral fracture risk

IntroductionSarcoma spinal metastases (SSM) are particularly difficult to manage given their poor response rates to chemotherapy and inherent radioresistance. We evaluated outcomes in a cohort of patients with SSM uniformly treated using single-fraction simultaneous-integrated-boost (SIB) spine stereotactic radiosurgery (SSRS). Materials and MethodsA retrospective review was conducted at a single tertiary institution treated with SSRS for SSM between April 2007-April 2023. 16–24 Gy was delivered to the GTV and 16 Gy uniformly to the CTV. Kaplan-Meier analysis was conducted to assess time to progression of disease (PD) with proportionate hazards modelling used to determine hazard ratios (HR) and respective 95 % confidence intervals (CI). Results70 patients with 100 lesions underwent SSRS for SSM. Median follow-up was 19.3 months (IQR 7.7–27.8). Median age was 55 years (IQR42-63). Median GTV and CTVs were 14.5 cm3 (IQR 5–32) and 52.7 cm3 (IQR 29.5–87.5) respectively. Median GTV prescription dose and biologically equivalent dose (BED) [α/β = 10] was 24 Gy and 81.6 Gy respectively. 85 lesions received 24 Gy to the GTV. 27 % of patients had Bilsky 1b or greater disease. 16 of 100 lesions recurred representing a crude local failure rate of 16 % with a median time to failure of 10.4 months (IQR 5.7–18) in cases which failed locally. 1-year actuarial local control (LC) was 89 %. Median overall survival (OS) was 15.3 months (IQR 7.7–25) from SSRS. Every 1 Gy increase in GTV absolute minimum dose (DMin) across the range (5.8–25 Gy) was associated with a reduced risk of local failure (HR = 0.871 [95 % CI 0.782–0.97], p = 0.009). 9 % of patients developed vertebral compression fractures at a median of 13 months post SSRS (IQR 7–25). ConclusionThis study represents one of the most homogenously treated and the largest cohorts of patients with SSM treated with single-fraction SSRS. Despite inherent radioresistance, SSRS confers durable and high rates of local control in SSM without unexpected long-term toxicity rates.

TRImodal DEfinitive invasive vagiNal carcinoma Treatment (TRIDENT protocol): how a standardized approach may change prognostic outcomes

ObjectiveVaginal carcinoma is a rare malignancy accounting for 1–2% of all gynecological cancers. Surgery has a limited role, while definitive radiotherapy–chemotherapy followed by interventional radiotherapy is considered a valid alternative....

Oligometastatic sarcoma treated with Curative intent Ablative Radiotherapy (OSCAR): A multicenter study on behalf of AIRO (Italian association of Radiotherapy and clinical Oncology)

Background and purposeStereotactic Ablative Radiotherapy (SABR) is emerging as a valid alternative to surgery in the oligometastatic setting in soft tissue sarcomas (STS), although robust data are lacking. The aim of this study is to evaluate toxicity and efficacy of SABR in oligometastatic STS. Materials and methodsThis is a retrospective multicenter study including adult patients affected by stage IV STS, treated with SABR for a maximum of 5 cranial or extracranial metastases in up to 3 different organs. SABR was delivered with ablative purposes. Study endpoints were overall survival (OS), local control (LC), distant progression free survival (DPFS), time to polymetastatic progression (TTPP), time to new systemic therapy (TTNS) and toxicity. ResultsFrom 10 Italian RT centers, 138 patients (202 metastases) treated between 2010 and 2022 were enrolled in the study. Treatment was generally well tolerated, no acute or late toxicity ≥ G3 was recorded. Median follow up was 42.5 months. Median OS was 39.7 months. Actuarial OS at 1 and 2 years was 91.5 % and 72.7 %. Actuarial LC at 1 and 2 years was 94.8 % and 88.0 %. Median DPFS was 9.7 months. Actuarial DPFS at 1 and 2 years was 40.8 % and 19.4 %. ConclusionSABR is a safe and effective approach for the treatment of oligometastatic sarcoma. One out of 5 patients is free of progression at 2-years.

Phase II Trial of Five-Fraction Accelerated Partial Breast Irradiation Using Noninvasive Image-Guided Breast Brachytherapy

NIBB has potential advantages over other APBI techniques by delivering highly conformal radiation with minimal collateral dose to the heart and lung compared with external beam techniques, but unlike other brachytherapy techniques NIBB is non-invasive. Previous data has shown encouraging outcomes using a 10-fraction regimen. To improve efficiency, convenience, and cost, reduction in the fraction number is desirable. Final results of a prospective phase II trial are reported. NIBB APBI was delivered using 28.5Gy in 5 fractions daily over 1 week. Patient eligibility criteria required: invasive carcinoma ≤2.0 cm or DCIS ≤3.0 cm, ER positive (if invasive), lymph node negative, LVI absent, and lumpectomy with margins negative by 2mm. The primary endpoint was grade ≥ 2 subcutaneous fibrosis/induration <30%. Secondary endpoints included any late toxicity, cosmetic outcome, and local control. 40 patients were treated with a median follow-up of 59.7 months. The mean age was 67 years (50-89 years) and tumor size was 1.0cm (0.3-2.0cm). 80% had invasive carcinoma. The mean breast separation with compression was 6.7cm (3.5-8.9cm). The 5-year actuarial local control was 96.6% and overall survival was 96.9%. Grade 2 and 3 late toxicities were 15% and 0%, respectively. The rate of grade 2 subcutaneous fibrosis/induration was 2.5% (+/-2.5%) meeting the study's primary endpoint. The most common late toxicity of any grade was skin telangiectasia; 22.5% grade 1 and 15% grade 2. Only breast separation was associated with telangiectasia risk, p=0.002. Overall cosmetic outcome was excellent, good, and fair/poor in 75%, 25%, and 0%, respectively. NIBB APBI delivered in 5 fractions results in a low rate of late toxicity and a high rate of good/excellent cosmetic outcomes. Telangiectasia risk can be minimized by keeping breast separation ≤7.0cm. The local failure rate was appropriately low. Further investigation of this technique is warranted.

Primary Total Laryngectomy for Endolaryngeal cT3-4M0 Squamous Cell Carcinoma: A STROBE Analysis.

To document 10-year oncologic outcome of primary total laryngectomy (TL) for patients with cT3-4M0 endolaryngeal squamous cell carcinoma (SCC). Observational inception cohort of 531 patients with isolated untreated endolaryngeal cT3-4M0 SCC review over 40 years using STROBE guideline. 94% of patients were followed until death or for a minimum of 10 years. Academic tertiary referral care center. All patients underwent primary TL. Prior tracheotomy, induction chemotherapy, thyroid gland resection, level II-IV neck dissection, level VI dissection, and postoperative radiation therapy were associated in 6%, 40%, 43%, 89%, 47%, and 74% of cases, respectively: The main objective was to determine the 10-year actuarial local control estimate. Accessory objectives comprised screening for clinical variables increasing the risk of local recurrence, and analysis of long-term oncologic consequences of local recurrence. The 10-year actuarial local control estimate was 89.7%. Local recurrence was salvaged in 11% of cases, resulting in 92% overall local control. On multivariate analysis, none of the study variables correlated with local recurrence. Local recurrence resulted in significantly reduced nodal control, distant metastasis control, and survival. Postoperative complications, persistent index SCC, intercurrent disease, and metachronous second primary cancer accounted for respectively 3%, 37%, 33%, and 28% of the 334 deaths noted during the 10 years following TL. The present study underscored the long-term oncologic efficacy of primary TL, the dangers of local recurrence, the key role of local control for survival, and the importance of a long-term oncologic watch policy. 3 Laryngoscope, 134:2288-2294, 2024.

Toxicity and Dosimetric Analysis of Reirradiation of Head and Neck Cancers with High Dose Rate Brachytherapy

Reirradiation (reRT) of recurrent or second primary head and neck cancers (HNC) after prior curative-intent external beam radiotherapy (EBRT) has historically achieved local control (LC) rates of 40-50% and been associated with high grade toxicity rates estimated at 25-50%. This study evaluated the hypothesis that patients with small reRT target volumes could be selected for high dose rate brachytherapy (HDR-BT) reRT and achieve similar LC without excess toxicity. Included were all patients with HNC squamous cell carcinoma treated with HDR-BT after having previously received curative-intent EBRT for primary HNC from 2000-2021. Patients were selected by a multidisciplinary tumor board to be appropriate candidates for HDR-BT reRT without EBRT generally for definitive or adjuvant treatment of small primary tumors without neck nodal metastases. Univariate analysis was performed using the logistic regression model. Survival outcomes were estimated with the Kaplan Meier method. Twenty-three patients were evaluated. Median follow up time was 19mo. Median age at time of HDR-BT was 64 years. Thirteen patients (57%) were treated for recurrent HNC, of which 7 were in the oral cavity (OC) and 6 were the oropharynx (OPX). Ten patients (43%) were treated for a second primary HNC, of which 5 were in the OC and 5 were in the OPX. Median time from completion of EBRT to HDR-BT was 41 (IQR 14-73) mo. Within their reRT course, 11 patients (48%) were treated with HDR-BT after resection, 9 patients (39%) received concurrent hyperthermia, and 7 patients (30%) received chemotherapy. HDR-BT regimens included 600cGy x5 (N = 11), 600cGy x6 (N = 6), 450cGy x8 (N = 1), 1500cGy x1 (N = 1),1000cGy x1 (N = 1), 500cGy x8 (N = 1), and 700cGy x5 (N = 1). One patient who was treated with two implants received 450cGy x 3 followed by 475cGy x5. A median of 5 brachytherapy catheters were used. Actuarial 2-year LC and overall survival rate was 68% and 62%, respectively. Of the 17 HDR-BT reRT plans available for review, median (IQR) target volume was 15.8 (10.6-34.9) cc. Median (IQR) target V100% was 90.6 (89.4-90.0)%, V150% was 50.5 (49.7-54.4)%, and V200% was 25.4 (23.8-29.0)%. Median (IQR) target D90% was 30.1 (29.8-35.5) Gy, and median D1cc was 116.4 (100.5-171.4) Gy. The mandible dose [median (IQR)] was D2cc:15.1(9.48-18.9) Gy; D1cc:16.9(11.1-21.3) Gy; and D1%:18.8(13.4-22.7) Gy. Nine of the 23 patients (39%) experienced ≥G3 toxicity including fistula, soft tissue necrosis, osteoradionecrosis, ulcer, hemorrhage, and dysphagia requiring a chronic feeding tube. Target D90% was associated with ≥G3 toxicity (p = 0.045). For D90% greater than the median of 30Gy, 45% ≥G3 toxicity was observed. This study suggests that HDR-BT for reRT of small recurrent or second primary HNC can provide similar LC without excess high-grade toxicities as compared to historical outcomes with EBRT reRT. Delivery of equivalent doses higher than 30Gy in 5 fractions should be approached with caution.

Correlation of Dose Volume Parameters with Dysphagia and Pharyngeal Constrictor Muscle Thickness in Dysphagia Optimized IMRT

Reduced radiation dose to the pharyngeal constrictor muscles (PCM) using dysphagia optimized intensity-modulated RT (DO-IMRT) is associated with improved swallowing outcomes in oropharyngeal cancers (OPCs). Purpose was to evaluate the relationship between dose of radiation delivered and acute dysphagia in patients with OPC treated with IMRT, after delineation of PCM. Twenty-five patients with newly diagnosed OPC who underwent definitive IMRT with concurrent cisplatin were included in the study. PCM mean dose < 50 Gy was used as the dose constraint. Target volume was divided into high, intermediate and low risk areas receiving doses in the range of 60-66 Gy, 54-58 Gy, 51-56 Gy in 30-33 fractions over 6-6.5 weeks, respectively. PCM dose-volume parameters were collected and logistic regression was used to analyze these data relative to percent weight loss during RT and duration of feeding tube use. Thickness of constrictor muscle in pre-treatment and 3 months post-therapy CT scan were assessed. Weekly assessment of dysphagia was based on RTOG toxicity gradings. Aim of the study was to evaluate the correlation between dysphagia grades with dose-volume parameters and PCM thickness. Median age was 55.0 years (mean 54.3) with 24 males and stage II:III-16:9 patients. Dmean to PCM was 49.86 Gy (range 48.22 -57.63) with median Dmax of 70.24 Gy. For patients with dysphagia (grade ≥1), V50 ranged from 48.2-57.23%, while in those with no dysphagia, it ranged from 47.92-52.18 % (Mean 51.36%). Nine patients needed feeding tube after RT end. Median feeding tube duration was 64 days. The correlation between Dmean ≥ 50 Gy and dysphagia at 1st, 2nd, 3rd and 6th month was found statistically significant (p < 0.01). Table 1 shows the Pearson correlation and P-value of the dosimetric parameters with dysphagia. The correlation of V50 was found statistically significant with grade of dysphagia at 3rd and 6th month post-treatment (p<0.001). The mean thickness range and median thickness of constrictors before and 3 months after treatment were 1.8-3.2 mm, 2.4 mm, and 2.8-6.2 mm,4.1 mm, respectively. The increase in thickness of constrictor muscle correlated significantly (p<0.05) with dysphagia grades and also with V50, V60 and Dmean (p<0.001) but no statistical significance was seen with Dmax (p = 0.232). With a median follow-up of 18 months (range 7-24), 1-year actuarial local control was 92%. DO-IMRT may prove beneficial in the OPC by preventing dysphagia and aspiration post therapy and hence improving the quality of life of patients. Dmean ≥ 50Gy, V50 > 51.4% and V60 > 35.5% are the parameters correlating significantly with dysphagia (p<0.001) and change in mean thickness of PCM (p<0.001).

Symptomatic Posttreatment Edema after Stereotactic Radiotherapy for Intracranial Meningiomas: Patterns and Predictive Factors

Symptomatic posttreatment edema (SPTE) is a complication that may develop after radiotherapy for intracranial meningiomas. Our study aims at reviewing rates of SPTE in a large cohort of a single institution and identifying possible predictive factors. We retrospectively analyzed data of 293 patients with 304 intracranial meningiomas irradiated at our institution between 2005 and 2018. We evaluated rates of SPTE and investigated numerous factors by univariate and multivariate analysis. Kaplan Meier analysis was used for estimation of actuarial local control and overall survival. Median age was 60 years. Meningiomas were treated with fractionated stereotactic radiation therapy (70%), single fraction stereotactic radiosurgery (24%) or fractionated stereotactic radiosurgery (6%). Median imaging follow-up was 60 months, actuarial 10-year local control rate for patients with grade 1 meningiomas who received radiotherapy as definitive treatment was 99%. Local control at 5 years was 94% for grade 1 meningioma, 57% and 53% for grade 2 and 3 respectively. Sixteen patients (5.5%) developed SPTE, median time to onset was 3 months (range, 1-26 months). On univariate analysis, age > 60 years (p > 0.03), pre-treatment peritumoral edema (p = 0.014), medline location (p = 0.018), tumor size > 30 mm (p = 0.015) and grade 2 histology (p = 0.03) were predictive of SPTE. On multivariate analysis, only tumor location and size remained statistically significant. Based on our results, patients at high risk of SPTE can be identified based on patient and tumor characteristics. The best treatment technique in high-risk patients is yet to be defined.

The Role of Stereotactic Radiotherapy in Deferring the Need for Systemic Therapies in Patients with Progressive Oligometastatic Iodine-Refractory Thyroid Cancer

Differentiated thyroid cancer (DTC) is usually associated with a good prognosis, although development of metastases in iodine-refractory patients adversely affects quality of life and survival. The advent of tyrosine-kinase inhibitors drugs (TKI) allowed for a significant improvement in patients' outcome: however, in case of oligometastatic disease, a locoregional ablative approach such as Stereotactic Radiation Therapy (SBRT) may be proposed. The aim of our study is to assess if SBRT in oligometastatic DTC patients could effectively control tumor progression and possibly defer the need of systemic therapies. We retrospectively analyzed patients with differentiated oligometastatic iodine refractory thyroid cancer treated with SBRT in our Radiation Oncology Unit from 2011 to 2022. We collected demographics and treatment-related characteristics. Local Control (LC), Progression Free Survival (PFS), Overall Survival (OS) and the need for systemic therapy were evaluated. Patients with anaplastic histology, incomplete treatment or without follow-up information were excluded. Twenty-two patients were included in our analysis, accounting for 63 tumors: 26 were located in bones (41,2%), 21 in lymph nodes (33,3%), 7 in the brain (11,1%), 6 in the lungs (9,5%) and 3 visceral (4,7%). SBRT was delivered in 1-8 fractions, with a median dose of 30Gy (range 24-60Gy). Median follow-up was 36,8 months (range 6,1-130,9 months). After SBRT we observed a complete response in 29 lesions (46,0%), partial response in 20 (31,7%), stable disease in 13 (20,6%) and only 1 progressive lesion (1,6%). We observed 10 local recurrences (15,8%) with an actuarial LC of 92,4% and 76,1% at 24 and 48 months respectively, while PFS was 62,8% and 52,3% at 12 and 24 months respectively. The OS at 24 and 48 months was 89,2% and 82,3% respectively. Patients with oligoprogressive disease were treated with further SBRT, while patients with polymetastatic progression of disease or oligoprogression not suitable for ablative treatment received systemic therapy. Eleven patients (50%) needed to start TKI treatment (6 Lenvatinib, 3 Sunitinib and 2 Sorafenib) for progressive disease: median time to first systemic treatment from SRT was 18,5 months (range 0,5-67 months). At the time of this analysis, 11 patients (50%) were still without systemic therapy, showing a good disease control after a median follow-up of 26,2 months (range 5,7-83). Freedom from systemic therapy rate from the time of SBRT was 85,6% and 57,6% at 12 and 24 months respectively. In our experience, SBRT yields satisfying local control rates in oligometastatic Iodine-refractory DTC, potentially allowing for a deferral of systemic therapies, and should always be considered in these patients.

Predictive Value of Tumor Volume on Local Control in Hepatocellular Carcinoma Treated with Image Guided Hypofractionated Radiation Treatment

External beam radiation treatment (EBRT) is an important local treatment in liver-confined hepatocellular carcinoma (HCC) patients who are not candidates for curative therapy. EBRT dose, technique and prognostic factors are evolving. We hypothesized that tumor volume to liver volume ratio can be a predictor of local control (LC) in patients treated with hypo-fractionated radiation (HFRT) in HCC MATERIALS/METHODS: We retrospectively reviewed 50 patients of HCC treated with HFRT at our institution. HFRT schedule was chosen such that the radiation dose to the remaining liver and other organs at risk (OAR) met the standard dosimetric constraints. Image guided techniques were used for motion management, internal target volume (ITV) and planning target volume (PTV) delineation. Tumor to Liver Ratio (TLR) was defined as ratio of PTV volume to whole liver volume. TLR ≤ 0.3 was considered as low volume disease and TLR > 0.3 was considered as high-volume disease. The radiation dose ranged from 45 Gy to 67.5 Gy in 5 - 15 fractions. The biologically equivalent dose (BED) for tumor ranged from 58.5 Gy10 to 100 Gy10. Local control (LC) was evaluated by Kaplan-Meier analysis, with log-rank test for groups stratified as per TLR. Multivariate Cox regression analysis was performed to identify additional prognostic factors. The mean duration of follow-up was 24 months. The median age was 69 years (range 50 - 90) and 76% were males. 32 patients had CP-A class cirrhosis while 17 had CP-B and 1 had CP-C class. BCLC stage A, B, C and D was seen in 2, 14, 33 and 2 patients, respectively. Portal vein thrombosis was present in 9 patients and prior trans-arterial chemo embolization (TACE) was done in 23 patients. The median volume of PTV was 551 cc (range 52 - 1990 cc). The TLR ranged from 0.04 - 0.67 with a median of 0.29. The median BED radiation dose was 78.4 Gy10 (range - 58.5 Gy10 to 100 Gy10). Nine patients had local recurrence with overall LC rate of 82%. The LC was better in low volume tumors, with the TLR cut-off of 0.3 as a significant factor associated with LC (p = 0.007). The 1-year actuarial LC with TLR ≤ 0.3 was 88% as compared 61% in TLR of > 0.3 (p = 0.007). BED ≥60 Gy10 was associated with better 1 year LC as compared to BED < 60 Gy10 (89% vs 62%; p = 0.11). ALBI grade 1 was associated with better 1 year LC as compared to ALBI grade 2 (80% versus 75%; p = 0.40). On multivariate analysis, high volume disease and TLR >0.3 were significant prognostic factor for LC. HFRT has good 1-year local control of 82% in carefully selected unresectable HCC. Radiation with BED greater than 60 Gy10 and ALBI grade 1 showed a trend towards better LC. Smaller tumors had better LC with a PTV to liver ratio (TLR) of < 0.3. This information can help in identifying the poor responders, intensifying the radiation treatment and adding additional therapy to improve the oncological outcomes.