Esophageal Toxicity Research Articles

Adjuvant modern radiotherapy in resected pN2 NSCLC patients: results from a multicentre retrospective analysis on acute and late toxicity on behalf of AIRO thoracic oncology study group: the RAC-TAC study.

Recently, the PORT-C and LUNG-ART trials, which evaluated the role of postoperative radiation therapy (PORT), have significantly altered the treatment landscape for NSCLC pN2 patients who previously underwent surgery. In response, the Italian Association of Radiotherapy and Oncology Thoracic Oncology study group has initiated an observational multicenter trial to assess both acute and late toxicities of PORT in pN2 NSCLC patients treated with modern techniques. Data on NSCLC patients submitted to PORT after radical surgery treated between 2015 and 2020 in six Italian Centers were collected. Heart, lung, and esophageal acute and late toxicities have been retrospectively analyzed and related to radiation therapy dosimetric parameters. Furthermore, loco-regional control, distant metastasis and overall survival have been analyzed. A total of 212 patients with a median age of 68years from six different centers were included in this analysis (142 males and 70 females). Prior to undergoing PORT, 96 patients (45.8%) had a history of heart disease, 110 patients (51.9%) had hypertension, and 51 patients (24%) had COPD. Acute toxicity was observed in 147 patients (69.3%), with lung toxicity occurring in 93 patients (G1 in 70 patients, G2 in 17 patients, and G3 in 4 patients), esophageal toxicity in 114 patients (G1 in 89 patients, G2 in 23 patients, and G3 in 1 patient), and cardiac toxicity in 4 patients (G1 in 2 patients and G3 in 2 patients). Late side effects were found in 60 patients (28.3%), predominantly involving the lungs (51 patients: 32 G1, 11 G2, and 1 G3) and the esophagus (11 patients: 8 G1 and 3 G2), with no reported late cardiac side effects. Various clinical and dosimetric parameters were found to correlate with both acute and chronic toxicities. Over a median follow-up period of 54months, 48 patients (22.6%) showed locoregional disease relapse, 106 patients (50%) developed distant metastases, and 66 patients (31.1%) died. RAC-TAC retrospective multicentric study showed the low toxicity of PORT when advanced technology is used. At the same time, it's noteworthy to underline that 50% of the patients develop distant recurrences in the follow up.

Phase II Trial Assessing Toxicity of Personalized Response-Based Radiation Treatment in Patients with Locally Advanced Non-Small Cell Lung Cancer

IntroductionLocal failure rates after treatment for locally advanced non-small-cell lung cancer (NSCLC) remain high. Efforts to improve local control with uniform dose-escalation or dose-escalation to mid-treatment PET-avid residual disease have been limited by heightened toxicity. This trial aimed to refine response-based adaptive radiation (RT) and minimize toxicity by incorporating FDG-PET and V/Q SPECT imaging mid-treatment. Methods47 patients with Stage IIA-III unresectable NSCLC were prospectively enrolled in this single-institution trial (NCT02492867). Patients received concurrent chemoradiation with personalized response-based adaptive RT over 30 fractions incorporating V/Q SPECT and FDG-PET. The first 21 fractions (46.2Gy at 2.2 Gy/fraction) were delivered to the tumor while minimizing dose to SPECT-defined functional lung. The plan was then adapted for the final 9 fractions (2.2-3.8Gy/fraction) up to a total of 80.4Gy, based on mid-treatment FDG-PET tumor response to escalate dose to residual tumor while minimizing dose to SPECT-defined functional lung. Non-progressing patients received consolidative carboplatin/paclitaxel or durvalumab. The primary endpoint of the study was ≥ grade 2 lung and esophageal toxicities. Secondary endpoints included time to local progression, tumor response, and overall survival. ResultsAt one year post-treatment, the rates of grade 2 and grade 3 pneumonitis were 21.3% and 2.1%, respectively, with no difference in pneumonitis rates among patients who received and did not receive adjuvant durvalumab (p=0.74). While there were no grade 3 esophageal-related toxicities, 66.0% of patients experienced grade 2 esophagitis. 1- and 2-year local control rates were 94.5% (95% CI, 87.4% - 100%) and 87.5% (95% CI, 76.7% - 100%), respectively. Overall survival was 82.8% (95% CI, 72.6% -94.4%) at 1 year and 62.3% (95% CI, 49.6%-78.3%) at 2 years. ConclusionsResponse-based adaptive dose-escalation accounting for tumor change and normal tissue function during treatment provided excellent local control, comparable toxicity to standard chemoradiation, and did not increase toxicity with adjuvant immunotherapy.

Dosimetric and NTCP advantages of robust proton therapy over robust VMAT for Stage III NSCLC in the immunotherapy era

AimsTo assess the robustness and to define the dosimetric and NTCP advantages of pencil-beam-scanning proton therapy (PBSPT) compared with VMAT for unresectable Stage III non-small lung cancer (NSCLC) in the immunotherapy era. Material and methods10 patients were re-planned with VMAT and PBSPT using: 1) ITV-based robust optimization with 0.5 cm setup uncertainties and (for PBSPT) 3.5 % range uncertainties on free-breathing CT 2) CTV-based RO including all 4DCTs anatomies. Target coverage (TC), organs at risk dose and TC robustness (TCR), set at V95%, were compared. The NTCP risk for radiation pneumonitis (RP), 24-month mortality (24MM), G2 + acute esophageal toxicity (ET), the dose to the immune system (EDIC) and the left anterior descending (LAD) coronary artery V15 < 10 % were registered. Wilcoxon test was used. ResultsBoth PBSPT methods improved TC and TCR (p < 0.01). The mean lung dose and lung V20 were lower with PBSPT (p < 0.01). Median mean heart dose reduction with PBSPT was 8 Gy (p < 0.001). PT lowered median LAD V15 (p = 0.004).ΔNTCP > 5 % with PBSPT was observed for two patients for RP and for five patients for 24 MM. ΔNTCP for ≥ G2 ET was not in favor of PBSPT for all patients. PBSPT halved median EDIC (4.9/5.1 Gy for ITV/CTV-based VMAT vs 2.3 Gy for both ITV/CTV-based PBSPT, p < 0.01). ConclusionsPBSPT is a robust approach with significant dosimetric and NTCP advantages over VMAT; the EDIC reduction could allow for a better integration with immunotherapy. A clinical benefit for a subset of NSCLC patients is expected.

Evidence-based clinical recommendations for hypofractionated radiotherapy: exploring efficacy and safety - Part 2. Lung (non-small cell lung cancer).

Several recent studies have investigated the use of hypofractionated radiotherapy (HFRT) for various cancers. However, HFRT for non-small cell lung cancer (NSCLC) with or without concurrent chemotherapy is not yet widely used because of concerns about serious side effects and the lack of evidence for improved treatment results. Investigations of HFRT with concurrent chemotherapy in NSCLC have usually been performed in single-arm studies and with a small number of patients, so there are not yet sufficient data. Therefore, the Korean Society for Radiation Oncology Practice Guidelines Committee planned this review article to summarize the evidence on HFRT so far and provide it to radiation oncology clinicians. In summary, HFRT has demonstrated promising results, and the reviewed data support its feasibility and comparable efficacy for the treatment of locally advanced NSCLC. The incidence and severity of esophageal toxicity have been identified as major concerns, particularly when treating large fraction sizes. Strategies, such as esophagus-sparing techniques, image guidance, and dose constraints, may help mitigate this problem and improve treatment tolerability. Continued research and clinical trials are essential to refine treatment strategies, identify optimal patient selection criteria, and enhance therapeutic outcomes.

Association of Radiation-Induced Acute Esophagitis With Dosimetric Parameters of Oesophagus in Breast Carcinoma Patients Receiving Supraclavicular Nodal Irradiation.

We conducted this investigation to ascertain the dosimetric properties such as the mean and maximum radiation dosage during radiotherapy as well as the extent of radiation exposure to the esophagus. These factors can potentially impact the development of esophagitis in breast cancer patients undergoing supraclavicular radiation. From January to June 2023, an observational study was conducted at Bangabandhu Sheikh Mujib Medical University in Bangladesh. The patients received radiation therapy (40.05 Gy in 15 parts) to the chest wall and supraclavicular node for three weeks. We were able to guess the following from the dose volume histogram (DVH) data: the length of the esophagus in the treatment area (i.e., the size of the esophagus that was visible on the planning CT scan), the maximum dose (Dmax), the mean dose (Dmean), and the volume of the 10Gy (V10Gy) and 20Gy (V20Gy) doses that were given to the esophagus. During radiotherapy, patients were checked on once a week, and the radiotherapy oncology group was used to evaluate and grade esophagitis Results: Patients with left-sided breast cancer showed a higher Dmean, Dmax, and length of the esophagus compared to those with right-sided breast cancer. Specifically, the Dmean was 6.7 (±2.1) Gy, the Dmax was 39.2 (±1.5) Gy, and the length of the esophagus was 6.1 (±1.2) Gy. Patients with left breast cancer had elevated V10Gy and V20Gy values for the esophagus, but the difference was not statistically significant. The incidence of V10Gy for right-sided breast cancer and left-sided breast cancer was 4.2% (±2.6%) and 19.8% (±9.2%), respectively. The V20Gy was 2.4% (±0.9%) for right-sided breast cancer and 13.09% (±5.0%) for left-sided breast cancer Conclusion: In conclusion, there is a strong association between the mean oesophageal dose and radiation to the left supraclavicular region following surgery in women with breast cancer and acute esophagitis. We can reduce esophageal toxicity by prescribing dose restrictions and performing precise delineation of the esophagus.

1480: Dose-response of oesophageal toxicity after thoracic re-irradiation with or without chemotherapy

1480: Dose-response of oesophageal toxicity after thoracic re-irradiation with or without chemotherapy

Durvalumab impacts progression-free survival while high-dose radiation >66 Gy improves local control without excess toxicity in unresectable NSCLC stage III: Real-world data from the Austrian radio-oncological lung cancer study association registry (ALLSTAR)

BackgroundChemo-radioimmunotherapy with total radiation doses of 60–66 Gy in 2 Gy fractions is the standard of care for non-small cell lung cancer (NSCLC) UICC stage III. The Austrian radio-oncological lung cancer study association registry (ALLSTAR) is a prospective multicentre registry intended to document clinical practice at the beginning of the Durvalumab era. Patients and methodsPatients were eligible if they had pathologically verified unresectable NSCLC stage III with a curative treatment option. Chemo-radiation combined with immunotherapy was performed according to local treatment practices. The endpoints were local control (LC), progression-free survival (PFS) and toxicity. ResultsBetween 2020/03 and 2023/04, 12/14 (86 %) Austrian radiation-oncology centres recruited 188 patients (median 17, range: 1–89). PD-L1 testing was performed in 173/188 (93 %) patients. The median interval between the end of chemoradiotherapy and start of Durvalumab was 14 days (range: 1–65). About 40 % (75/188) of the patients received a total radiation dose of > 66 Gy (range: 67.1–100), which improved 2-year LC (86 % versus 60 %, HR = 0.41; 95 %-CI: 0.17–0.98; log-rank p-value < 0.05). Median PFS for patients with Durvalumab was 25.8 months (95 %-CI: 21.9-not reached) compared to 15.7 months (95 %-CI: 13.2–27.8) for those without (HR = 1.88; 95 %-CI: 1.16–3.05; log-rank p-value < 0.01). The rates of esophageal and pulmonary toxicities were 34.6 % and 23.9 %, respectively, including one case of grade 4 pneumonitis. In the subcohort of 75 patients who received > 66 Gy, 19 (25 %) cases of pulmonary toxicity grades 1–3 were observed. ConclusionWhile Durvalumab impacts PFS, LC can be improved by total radiation doses > 66 Gy without excess toxicity.

Re-irradiation spine stereotactic body radiotherapy following high-dose conventional radiotherapy for metastatic epidural spinal cord compression: a retrospective study

Purpose We aimed to evaluate the efficacy and safety of re-irradiation stereotactic body radiation therapy (SBRT) in patients with metastatic epidural spinal cord compression (MESCC) following high-dose conventional radiotherapy.Materials and methods Twenty-one patients met the following eligibility criteria: with an irradiation history of 50 Gy2 equivalent dose in 2-Gy fractions (EQD2) or more, diagnosed MESCC in the cervical or thoracic spines, and treated with re-irradiation SBRT of 24 Gy in 2 fractions between April 2018 and March 2023. Prior treatment was radiotherapy alone, not including surgery. The primary endpoint was a 1-year local failure rate. Overall survival (OS) and treatment-related adverse events were assessed as the secondary endpoints. Since our cohort includes one treatment-related death (TRD) of esophageal perforation, the cumulative esophageal dose was evaluated to find the dose constraints related to severe toxicities.Results The median age was 68, and 14 males were included. The primary tumor sites (esophagus/lung/head and neck/others) were 6/6/7/2, and the median initial radiotherapy dose was 60 Gy2 EQD2 (range: 50–105 Gy2, 60–70/ > 70 Gy2 were 11/4). Ten patients underwent surgery followed by SBRT and 11 SBRT alone. At the median follow-up time of 10.4 months, 17 patients died of systemic disease progression including one TRD. No radiation-induced myelopathy or nerve root injuries occurred. Local failure occurred in six patients, with a 1-year local failure rate of 29.3% and a 1-year OS of 55.0%. Other toxicities included five cases of vertebral compression fractures (23.8%) and one radiation pneumonitis. The cumulative esophageal dose was recommended as follows: Dmax < 203, D0.035 cc < 187, and D1cc < 167 (Gy3 in biological effective dose).Conclusion Re-irradiation spine SBRT may be effective for selected patients with cervical or thoracic MESCC, even with high-dose irradiation histories. The cumulative dose assessment across the original and re-irradiated esophagus was recommended to decrease the risk of severe esophageal toxicities.

Early Experience With Two-Fraction Spine Stereotactic Body Radiation Therapy in Treating Spinal Metastases.

Spinal metastases are common in metastatic cancer, affecting around 40% of patients. The primary treatment involves radiation therapy, transitioning from conventional external beam radiation therapy (EBRT) to stereotactic body radiation therapy (SBRT) for its superior, durable response. While spine SBRT has gained popularity in the United States, Level I evidence supporting it over EBRT is limited to a Canadian trial using a 2-fraction SBRT regimen. We present our findings from one of the earliest US experiences of 2-fraction spine SBRT for spinal metastases. A retrospective analysis of patients with metastatic spine cancer receiving 2-fraction spine SBRT at a single center was conducted. Patients received treatment based on Level 1 evidence (24Gy in 2 fractions). Follow-up records were assessed for local control outcomes and toxicity. Twenty patients since August 2022 have been treated with 2-fraction spine SBRT. Most patients were treated at 1 (45%) or 2 (40%) spinal levels, with the thoracic (55%) and lumbar (50%) spine being the most common locations. Common primary sites included the lung (30%), breast (20%), esophagus (15%), and prostate (10%). The rate of local control was 100%, while the rate of vertebral compression fracture was 15%. No esophageal or bowel toxicity occurred, and no fractures required intervention. These findings suggest that 2-fraction spine SBRT is safe and effective, consistent with existing Level I evidence. Our local control rate exceeding 95% aligns with the literature, indicating the feasibility and achievability of implementing this approach in the United States over a short period of time.

Dosimetric rationale and preliminary experience in proton plus carbon-ion radiotherapy for esophageal carcinoma: a retrospective analysis

BackgroundConcurrent chemoradiotherapy has been standard of care for unresectable esophageal carcinoma. There were no reports on proton radiotherapy (PRT) plus carbon-ion radiotherapy (CIRT) with pencil beam scanning (PBS) for esophageal carcinoma. This study evaluated the tolerability and efficiency of proton and sequential carbon-ion boost radiotherapy for esophageal carcinoma.MethodsFrom April 2017 to July 2020, 20 patients with primary esophageal carcinoma at stages II–IV were treated with PRT plus sequential CIRT with PBS. A median relative biological effectiveness-weighted PRT dose of 50 Gy in 25 fractions, and a sequential CIRT dose of 21 Gy in 7 fractions were delivered. Respiratory motion management was used if the tumor moved > 5 mm during the breathing cycle. A dosimetric comparison of photon intensity-modulated radiotherapy (IMRT), PRT, and CIRT was performed. The median times and rates of survivals were estimated using the Kaplan–Meier method. Comparison of the dose-volume parameters of the organs at risk employed the Wilcoxon matched-pairs test.ResultsTwenty patients (15 men and 5 women, median age 70 years) were included in the analysis. With a median follow-up period of 25.0 months, the 2-year overall survival and progression-free survival rates were 69.2% and 57.4%, respectively. The patients tolerated radiotherapy and chemotherapy well. Grades 1, 2, 3, and 4 acute hematological toxicities were detected in 25%, 30%, 10%, and 30% of patients, respectively. Grades 3–5 acute non-hematological toxicities were not observed. Late toxicity events included grades 1, 2, and 3 in 50%, 20%, and 10% (pulmonary and esophageal toxicity in each) of patients. Grades 4–5 late toxicities were not noted. PRT or CIRT produced lower doses to organs at risk than did photon IMRT, especially the maximum dose delivered to the spinal cord and the mean doses delivered to the lungs and heart.ConclusionsPRT plus CIRT with PBS appears to be a safe and effective treatment for esophageal carcinoma. PRT and CIRT delivered lower doses to organs at risk than did photon IMRT. Further investigation is warranted.

Personalized Accelerated ChEmoRadiation (PACER) for Lung Cancer: Protocol for a Bayesian Optimal Phase I/II Trial

IntroductionPrior attempts to escalate radiation dose for non–small cell lung cancer (NSCLC) have not improved survival. Given the high risk for cardiopulmonary toxicity with treatment and heterogenous presentation of locally advanced NSCLC, it is unlikely that a single dose regimen is optimal for all patients. This phase I/II trial aims to evaluate a novel treatment approach where the level of accelerated hypofractionation is determined by the predicted toxicity from dose to organs at risk (OARs). MethodsPatients ≥ 18 years old with lung cancer planned for fractionated radiotherapy to the lung with concurrent chemotherapy will be eligible. Radiation therapy (RT) will be delivered to a total dose of 60 to 66 Gy in 30, 25, or 20 fractions depending on the ability to meet constraints to key organs at risk including the lungs, heart, and esophagus. The primary endpoint is high grade pulmonary, esophageal, or cardiac toxicity. A Bayesian optimized design is used to determine stopping boundaries and evaluate the primary endpoint. ConclusionPACER will evaluate the safety and feasibility of personalized accelerated chemoradiotherapy for lung cancer.

Outcomes following hypofractionated radiation therapy alone for surgically unfit early esophageal squamous cell carcinoma patients; a retrospective single center analysis

Background and purposeTo report the feasibility of hypofractionated radiation therapy (RT) alone for early stage esophageal squamous cell carcinoma (ESCC) patients. Materials and methodsThe oncologic outcomes of 60 cT1-2 N0 ESCC patients who received hypofractionated RT (54 ∼ 60 Gy by 3.0 Gy per fraction) from 2004 to 2018 were retrospectively evaluated. ResultsThe 5-year rates of local control (LC), progression-free survival, cancer-specific survival, and overall survival were 81.1 %, 44.2 %, 73.7 %, and 54.5 %, respectively. In Cox regression analysis, tumor length < 3 cm was correlated with favorable LC (HR 0.167, p = 0.090), and the 5-year LC rates were 95.7 % and 72.0 % in < 3 cm and ≥ 3 cm subgroups, respectively (p = 0.053). Grade ≥ 2 esophagitis was observed in 44 patients (73.3 %) and grade ≥ 2 esophageal strictures developed in five (8.3 %), respectively. The patients with ≥ 3 cm tumor more frequently suffered from grade ≥ 2 esophagitis (13/24 vs. 31/36, p = 0.006) and grade ≥ 2 esophageal stricture (0/24 vs. 5/36, p = 0.056), respectively. The patients with cT2 tumor suffered from grade ≥ 2 esophagitis more frequently than those with T1 tumor (29/44 vs. 15/16, p = 0.03). ConclusionsHypofractionated RT alone, with the merit of short treatment course, could be used as feasible option in treating the early stage ESCC patients who are unfit for surgical resection or chemoradiation. Especially, tumor length < 3 cm seems a good indication of this treatment scheme based on favorable LC rate with low incidence of esophageal toxicities.

Comparison of photon intensity modulated, hybrid and volumetric modulated arc radiation treatment techniques in locally advanced non-small cell lung cancer

Background and purposeThere is no consensus on the best photon radiation technique for non-small cell lung cancer (NSCLC). This study quantified the differences between commonly used treatment techniques in NSCLC to find the optimal technique. Materials and methodsTreatment plans were retrospectively generated according to clinical guidelines for 26 stage III NSCLC patients using intensity modulated radiation therapy (IMRT), hybrid, and volumetric modulated arc therapy (VMATC, and VMATV5 optimized for lower lung and heart dose). Plans were evaluated for target coverage, organs at risk dose (including heart substructures) and normal tissue complication probabilities (NTCP). ResultsThe comparison showed significant and largest median differences (>1 Gy or >5%) in favor of IMRT for the mediastinal envelope and heart (maximum dose), in favor of the hybrid technique for the lungs (V5Gy of the total lungs and V5Gy of the contralateral lung) and in favor of VMATC for the heart (Dmean), most of the substructures of the heart, and the spinal cord (maximum dose). The VMATV5 technique had significantly lower heart dose compared to the hybrid technique and significantly lower lung dose compared to the VMATC, combining both advantages in one technique. The mean ΔNTCP did not exceed the 2 percent point (pp) for grade 5 (mortality), and 10 pp for grade ≥2 toxicities (radiation pneumonitis and acute esophageal toxicity), but ΔNTCP was mostly in favor of VMATC/V5 for individual patients. ConclusionThis planning study showed that VMATV5 was preferred as it achieved low lung and heart doses, as well as low NTCPs, simultaneously.

Effect of Contralateral Esophagus Sparing in Hypofractionated Radiotherapy for Ultra-Central NSCLC

Esophageal toxicity is a known complication of radiotherapy (RT) for ultra-central lung tumors, with ∼5 - 15% of patients developing grade ≥3 esophagitis. Despite increasing adoption of hypofractionated regimens, there are no consensus recommendations for reducing esophageal toxicity in these patients. We previously demonstrated the utility of a novel contralateral esophagus sparing technique (CEST) in a prospective trial of patients with locally-advanced NSCLC receiving concurrent chemoRT (70 Gy/7 weeks). Whether CEST is effective for hypofractionated RT is unknown. The aims of this study were to identify outcomes and toxicities associated with use of CEST in patients receiving definitive hypofractionated RT to ultra-central lung tumors. We retrospectively analyzed the records of consecutive patients with ultra-central NSCLC who received definitive RT to a dose of ≥60 Gy with fraction size ≥3 Gy per day, from 1/1/2015 to 6/30/2022. The esophageal wall contralateral to the tumor was contoured as an avoidance structure. VMAT planning was used to ensure steep dose fall-off across the esophagus while maintaining full tumor coverage. Treatment was delivered using daily cone-beam CT guidance. Toxicity was graded using CTCAE v 4.0. Descriptive statistics were used to analyze outcomes. The study was approved by the IRB. We identified 45 patients with ultra-central NSCLC treated with definitive RT, with median follow-up of 27.3 months. Median age was 74.5 years old [57.6 - 88.2]. Median ECOG PS was 2 [1 - 3]. Twenty-three patients had PTVs located within 1 cm of the esophagus. Median ITV and PTV volumes were 17 cc [1.6 - 154 cc] and 43.6 cc [8.4 - 292 cc], respectively. Median total dose was 60 Gy [60 - 67.5 Gy] in 20 [10 - 20] fractions. Median esophageal Dmax was 24 Gy [2 - 66.7 Gy] for all patients and 36 Gy [12.3 - 66.7 Gy] for patients with tumors located within 1 cm of the esophagus. For the CE, median Dmax, V20 Gy and V25 Gy were 35.7 Gy [17 - 45.2 Gy], 2.1 cc [0 - 6.7 cc] and 0.95 cc [0 - 3 cc], respectively. There were no episodes of grade ≥2 esophagitis (95% CI, 0-7.9%). The rate of grade 1 esophagitis was 13.3% (6.2 - 26.1%). Esophageal Dmax was higher in patients who developed esophagitis (44.5 vs. 26.1 Gy, t = 2.5, p = 0.038). Two patients developed grade 2 pneumonitis (4.4%, 95% CI 0 - 10.5%). There were no episodes of grade ≥3 pulmonary toxicity. There were 3 (6.7%) local recurrences, with 2-year local recurrence rate of 4.4%. Use of CEST to minimize esophageal dose for treatment of ultra-central NSCLC is associated with reduced rates of esophagitis compared with historical controls, without compromising local control. This technique is readily adaptable for clinical practice. More data are needed to refine the empirically derived CE dose-volume constraints, especially for tumors directly abutting the esophagus.

Laryngo-Esophageal Dysfunction Free Survival of Chemoradiation for Cervical Esophageal Cancer

Chemoradiotherapy is often the treatment of choice for cervical esophageal cancer due to the invasiveness of surgery. However, toxicity after chemoradiotherapy often affects the quality of life related to swallowing and speech. This study evaluated laryngoesophageal dysfunction-free survival (LEDFS) in patients with cervical esophageal cancer, which has recently been used in head and neck cancer. We analyzed 59 patients with cervical esophageal cancer without distant metastases other than supraclavicular lymph node metastases who received radical chemoradiotherapy with 5-fluorouracilplus platinum between 2002 and 2018. Loco-regional control (LRC), overall survival (OS), LEDFS, metachronous esophageal cancer incidence rates, and late toxicities were evaluated. LEDFS events were defined as death, local recurrence, total or partial laryngectomy, tracheostomy for more than 2 years, and feeding tube use for more than 2 years, as recommended by the Larynx Preservation Consensus Panel. The Kaplan-Meier method was used to calculate survival rates. The generalized Wilcoxon test was used to compare the two groups. The Common Terminology Criteria for Adverse Events v5.0 was used to assess toxicities. The median age was 66 years (range, 38-83). There were 13 women and 46 men. Stage I, II, III, IVA, and IVB disease according to UICC 8th staging were 15, 9, 9, 10, and 16 patients, respectively. 22 received conventional radiotherapy and 37 received volumetric modulated arc therapy. The median total irradiation dose was 66 Gy. Platinum plus 5-fluorouracil chemotherapy was administered to all patients. The median follow-up for survivors was 87.5 months. The 5-year LRC, OS, and LEDFS rates were 54.2%, 48.9%, and 41.9%, respectively. The prognostic factors for OS were performance status (PS), hypopharyngeal extension, and clinical stage in univariate analysis and only clinical stage (hazard ratio [HR] 3.87, 95% Confidence interval [CI]: 1.52-9.87, p<0.01) in multivariate analysis; the prognostic factors for LEDFS were PS, hypopharyngeal extension and clinical stage in univariate analysis and hypopharyngeal extension (HR 2.38, 95% CI: 1.12-5.03, p = 0.02) and clinical stage (HR 4.07, 95% CI: 1.48-11.06, p<0.02) in multivariate analysis. Metachronous esophageal cancer was observed in 28.6% of patients at 5 years. As severe late toxicities, grade 3 pneumonitis, esophageal stricture, esophageal fistula, laryngeal stricture, and laryngeal edema were observed in 1 (2%), 1 (2%) and 4 (7%), 1 (2%) and 1 (2%), respectively. Grade 2 hypothyroidism was observed in 31 (53%) patients. Chemoradiation for cervical esophageal cancer showed good results. The prognostic factors for LEDFS were pharyngeal extension and clinical stage. Late esophageal and laryngeal toxicity, hypothyroidism, and metachronous esophageal cancer should be noted.

Improving knowledge-based treatment planning for lung cancer radiotherapy with automatic multi-criteria optimized training plans

Background Knowledge-based planning (KBP) is a method for automated radiotherapy treatment planning where appropriate optimization objectives for new patients are predicted based on a library of training plans. KBP can save time and improve organ at-risk sparing and inter-patient consistency compared to manual planning, but its performance depends on the quality of the training plans. We used another system for automated planning, which generates multi-criteria optimized (MCO) plans based on a wish list, to create training plans for the KBP model, to allow seamless integration of knowledge from a new system into clinical routine. Model performance was compared for KBP models trained with manually created and automatic MCO treatment plans. Material and Methods Two RapidPlan models with the same 30 locally advanced non-small cell lung cancer patients included were created, one containing manually created clinical plans (RP_CLIN) and one containing fully automatic multi-criteria optimized plans (RP_MCO). For 15 validation patients, model performance was compared in terms of dose-volume parameters and normal tissue complication probabilities, and an oncologist performed a blind comparison of the clinical (CLIN), RP_CLIN, and RP_MCO plans. Results The heart and esophagus doses were lower for RP_MCO compared to RP_CLIN, resulting in an average reduction in the risk of 2-year mortality by 0.9 percentage points and the risk of acute esophageal toxicity by 1.6 percentage points with RP_MCO. The oncologist preferred the RP_MCO plan for 8 patients and the CLIN plan for 7 patients, while the RP_CLIN plan was not preferred for any patients. Conclusion RP_MCO improved OAR sparing compared to RP_CLIN and was selected for implementation in the clinic. Training a KBP model with clinical plans may lead to suboptimal output plans, and making an extra effort to optimize the library plans in the KBP model creation phase can improve the plan quality for many future patients.

Explainable Artificial Intelligence to Identify Dosimetric Predictors of Toxicity in Patients with Locally Advanced Non-Small Cell Lung Cancer: A Secondary Analysis of RTOG 0617

Dosimetric predictors of toxicity in patients treated with definitive chemoradiation for locally advanced non-small cell lung cancer are often identified through trial and error. This study used machine learning (ML) and explainable artificial intelligence to empirically characterize dosimetric predictors of toxicity in patients treated as part of a prospective clinical trial. A secondary analysis of the Radiation Therapy Oncology Group (RTOG) 0617 trial was performed. Multiple ML models were trained to predict grade ≥3 pulmonary, cardiac, and esophageal toxicities using clinical and dosimetric features. Model performance was evaluated using the area under the curve (AUC). The best performing model for each toxicity was explained using the Shapley Additive Explanation (SHAP) framework; SHAP values were used to identify relevant dosimetric thresholds and were converted to odds ratios (ORs) with confidence intervals (CIs) generated using bootstrapping to obtain quantitative measures of risk. Thresholds were validated using logistic regression. The best-performing models for pulmonary, cardiac, and esophageal toxicities, outperforming logistic regression, were extreme gradient boosting (AUC, 0.739), random forest (AUC, 0.706), and naive Bayes (AUC, 0.721), respectively. For pulmonary toxicity, thresholds of a mean dose >18 Gy (OR, 2.467; 95% CI, 1.049-5.800; P=.038) and lung volume receiving ≥20 Gy (V20) > 37% (OR, 2.722; 95% CI, 1.034-7.163; P=.043) were identified. For esophageal toxicity, thresholds of a mean dose >34 Gy (OR, 4.006; 95% CI, 2.183-7.354; P < .001) and V20 > 37% (OR, 3.725; 95% CI, 1.308-10.603; P=.014) were identified. No significant thresholds were identified for cardiac toxicity. In this data set, ML approaches validated known dosimetric thresholds and outperformed logistic regression at predicting toxicity. Furthermore, using explainable artificial intelligence, clinically useful dosimetric thresholds might be identified and subsequently externally validated.

MO-0470 IMPT reduces esophageal and pulmonary toxicity compared to VMAT in stage II-IV NSCLC patients

MO-0470 IMPT reduces esophageal and pulmonary toxicity compared to VMAT in stage II-IV NSCLC patients

MO-0471 Post-radiotherapy G3+ esophageal toxicity predictors: Pooled data from 2,131 lung cancer patients

MO-0471 Post-radiotherapy G3+ esophageal toxicity predictors: Pooled data from 2,131 lung cancer patients

Stereotactic Body Radiation Therapy for Sarcoma Pulmonary Metastases.

Lung metastases are the most common form of distant failure for patients diagnosed with sarcoma with metastasectomy considered for some patients with limited metastatic disease and good performance status. Alternatives to surgery such as stereotactic body radiation therapy (SBRT) can be considered, though data are limited. We present outcomes after SBRT for sarcoma lung metastases. Fifty sarcoma patients with 109 lung metastases were treated with SBRT between 2005 and 2021. Outcomes evaluated included local control (LC), overall survival (OS), and toxicity including lung pneumonitis/fibrosis, chest wall toxicity, dermatitis, brachial plexus, and esophageal toxicity. Systemic therapy receipt before and after SBRT was recorded. SBRT schedules were divided into 3 cohorts: 30 to 34Gy/1fx (n=10 [20%]), 48 to 50Gy/4 to 5fx (n=24[48%]), and 60Gy/5fx (n=16[32%]). With a median follow-up of 19.5 months, 1/3-year LC rates were 96%/88% and 1/3-year OS 77%/50%, respectively. There was no differences between the 3 regimens in terms of LC, OS, or toxicity. Size >4cm was a predictor of worse LC ( P =0.031) and worse OS ( P = 0.039) on univariate analysis. The primary pattern of failure was new metastases (64%) of which the majority were in the contralateral lung (52%). One-year chemotherapy-free survival was 85%. Overall, 76% of patients did not require chemotherapy initiation or change of chemotherapy regimen after lung SBRT. Toxicity was reported in 16% of patients overall, including 25%, 20%, and 14% in the 30 to 34Gy/1fx, 48 to 50Gy/4 to 5fx, and 60Gy/5fx cohorts, respectively. SBRT outcomes for lung metastases from sarcoma demonstrate high rates of LC and are similar with different dose/fractionation regimens. Lung SBRT is associated with prolonged chemotherapy-free survival. Prospective validation of these results is warranted.