Predictors of lung injury during durvalumab maintenance therapy following concurrent chemoradiotherapy in unresectable locally advanced non-small cell lung carcinoma.

BACKGROUND: Based on the results of the PACIFIC trial, maintenance with durvalumab has emerged as the standard treatment following concurrent chemoradiotherapy in patients with unresectable locally advanced non-small cell lung carcinoma (NSCLC). However, adverse events attributed to durvalumab, especially lung injuries, including immune-related adverse events, and radiation pneumonitis, are concerning. This study retrospectively investigated the factors related to lung injury in patients receiving the PACIFIC regimen. METHODS: Patients with unresectable locally advanced NSCLC who received durvalumab maintenance therapy following concurrent chemoradiotherapy at Yokohama City University Medical Centre between July 2018 and March 2022 were included. Clinical data, volume of normal lung receiving 20 or 5 Gy or more (V20 or V5), planning target volume (PTV), and relative lung parenchyma volume in emphysematous lung receiving 20 or 5 Gy or more (RLPV20 or 5; V20 or V5/100-percentage of low-attenuation volume) were evaluated. RESULTS: Performance status (PS), V20, V5, PTV, RLPV20, and RLPV5 were significantly higher in the lung injury group in the univariate analysis. Furthermore, RLPV20 was the most significant factor in the lung injury group in the multivariate analysis comprising PS, PTV, V20, and RLPV20. CONCLUSION: RLPV20 and RLPV5 are useful in estimating lung inflammation. RLPV20 could be considered the most reliable risk factor for maintenance therapy with durvalumab following concurrent chemoradiotherapy in patients with unresectable locally advanced NSCLC.

Toxic Effects of Volume-modulated Arc Therapy for Esophageal Squamous Cell Cancer: Preliminary Clinical Results.

BACKGROUND/AIM: To evaluate the toxic effects associated with various factors, including the presence or absence of concurrent chemotherapy with volume-modulated arc therapy (VMAT) and dose parameters for esophageal cancer (EC), and to assess the safety and feasibility of the VMAT protocol. PATIENTS AND METHODS: Patients with EC who received definitive VMAT between December 2016 and December 2020 were retrospectively analyzed. VMAT plans were designed to deliver 60 Gy to the primary tumor, 54 Gy to high-risk sites, and 51.3 Gy to regional lymph node sites. Toxic effects were evaluated for esophagitis, neutropenia, esophageal stricture, pericardial effusion, radiation-associated pneumonia. RESULTS: Forty-five patients received concurrent chemoradiotherapy (CCRT), while 29 were treated with radiation therapy (RT) alone. The following grade 3 complications were detected: Neutropenia in four patients (5.4%), esophagitis in two (2.7%), and esophageal stricture in one (1.4%). Grade 4 or more complications were not observed. The median age of the CCRT group (67 years) was significantly lower than that of the RT-alone group (77 years) (p<0.0001). The incidence of esophagitis was significantly higher in the CCRT group (75.5%) than in the RT group (48.3%) (p=0.033). The univariate analysis identified increasing mean dose to the pericardium as a significant risk factor for pericardial effusion, and CCRT and performance status ≥1 as significant for radiation-associated pneumonia. These factors were not significant in the multivariate analysis. Neutropenia and esophageal stricture were not associated with any factor examined. CONCLUSION: VMAT alone and in CCRT performed with our protocol was safe and feasible in patients with esophageal squamous cell cancer.

Long-term Outcomes of Early-stage Non-stomach Gastrointestinal Mucosa-associated Lymphoid Tissue Lymphoma Treated With Radiation Therapy.

BACKGROUND/AIM: Non-stomach gastrointestinal mucosa-associated lymphoid tissue (MALT) lymphoma is rare, and there are only a few reports regarding radiation therapy (RT) for non-stomach gastrointestinal MALT lymphoma. There has been no established cure and no reports on RT use with long-term follow-up. Herein, we report a retrospective long-term investigation of early-stage non-stomach gastrointestinal MALT lymphoma. Our aim was to evaluate whether RT is a valid treatment option for this disease. PATIENTS AND METHODS: We retrospectively analyzed 6 patients who were diagnosed with early-stage non-stomach gastrointestinal MALT lymphoma and received RT. The median age was 66 years (range=38-89 years). The primary tumor originated from the duodenum in 2 patients and from the rectum in 4 patients. The RT dose was 30-34 Gy in 15-20 fractions to the involved site or field, depending on the case. RESULTS: The median follow-up time was 89.5 months (range=6-170). All patients had complete remission within 3 months after RT. The 5-year overall survival and progression-free survival rates were 83.3% and 100%, respectively. During the observation period, no patient had a confirmed recurrence. One patient died of causes unrelated to cancer or treatment. There were no late toxicities by RT. CONCLUSION: Our results show good long-term local control and no late toxicities requiring treatment. Moderate-dose RT was appropriate and well tolerated for early-stage non-stomach gastrointestinal MALT lymphoma.

Impact of Regional Lymph Node Irradiation on Reducing Lymph Node Recurrence in Esophageal Cancer Patients.

Background/Aim: To evaluate the preventive effects of regional lymph node irradiation on lymph node recurrence in esophageal cancer (EC). Patients and Methods: The study included 289 patients who received definitive radiotherapy for EC. The regional lymph node area of group 1 was determined as the area with the highest probability of lymph node metastasis and group 2 was determined as the area with the next highest probability of lymph node metastasis depending on the primary site of EC. Results: The patients in whom group 2 was completely included in the irradiated field had a significantly lower rate of recurrence of regional lymph node metastasis than those in whom group 2 was not or insufficiently included (p=0.0337). There was no significant difference in overall survival (p=0.4627) or disease-specific survival (p=0.6174) between the two groups. Conclusion: Regional lymph node irradiation did not have survival-prolonging effects but significantly reduced regional lymph node recurrence.

Sequential chemotherapy after definitive radiotherapy in markedly elderly patients with advanced esophageal cancer.

Background: Concurrent chemoradiotherapy (CCRT) is the standard treatment for advanced esophageal cancer, but it may be more invasive in the elderly and definitive radiotherapy (RT) alone may be selected. This study assessed the significance of sequential chemoradiotherapy (SCRT) in elderly esophageal cancer patients. Methods: We reviewed 87 patients aged 75 years and older, who were treated using definitive radiotherapy without concurrent chemotherapy for esophageal cancer. A total dose ranging from 50.4 to 63 Gy (median, 58.8) was delivered to the primary lesion and the involved lymph nodes. This study compared patients who received SCRT with those who received RT alone among 40 patients with stage III or IVA cancer. Descriptive statistics were calculated using Cox proportional hazards regression analysis and the generalized Wilcoxon test. Results: The total progression-free survival (TPFS), progression-free survival outside the irradiation field, and overall survival were significantly longer after SCRT (n = 15) than after definitive RT alone (n = 25; P = 0.0041 and 0.0098), whereas the progression-free survival in the irradiation field was not significantly different between the two groups. The TPFS was significantly shorter in patients who received RT alone than in those who received SCRT (P = 0.0372). There were no grade 4 or higher adverse events in the patients who received SCRT. Conclusion: SCRT was associated with a reduced relapse rate, suggesting that it should be considered for markedly elderly patients with advanced esophageal cancer.

Relationship Between Radiation Pneumonitis Following Definitive Radiotherapy for Non-small Cell Lung Cancer and Isodose Line.

BACKGROUND/AIM: It is important to identify radiation pneumonitis above Common Terminology Criteria for Adverse Events Grade 2 (G2) in order to safely continue durvalumab maintenance after chemoradiotherapy for advanced lung cancer. The aim of this study was to discover factors that predict pneumonitis above G2. PATIENTS AND METHODS: A follow-up computed tomography (CT) image was superimposed on the planning CT image using deformable image registration (DIR). The pneumonitis area was contoured on follow-up CT after DIR and the dose-volume histogram parameters of the contoured pneumonitis area were calculated. RESULTS: V5 (Percentage of total volume receiving ≥5 Gy) to V50 of pneumonitis were significantly lower in patients with G2 pneumonitis than in those with G1 pneumonitis. The pneumonitis V15 was the most significant. The group with pneumonitis V15 <87.10% had significantly more G2 pneumonitis than the group with pneumonitis V15 ≥87.10%. CONCLUSION: Pneumonitis V15 <87.10% was a risk factor for G2 pneumonitis.

Radiotherapy for non-gastric intestinal versus gastric MALT lymphoma: a comparison of treatment outcomes.

BACKGROUND: Radiotherapy is often used for treating patients with gastric mucosa-associated lymphoid tissue (MALT) lymphomas who fail to respond to Helicobacter pylori eradication. However, non-gastric intestinal MALT lymphoma is rare, and no standard therapeutic strategies have been established. This study was designed to assess the long-term prognosis of non-gastric intestinal MALT lymphoma treated with radiotherapy and to compare the outcomes with that of post-radiotherapy gastric MALT lymphoma. METHODS: The study included 34 patients with stage I EA gastrointestinal MALT lymphoma according to the Ann Arbor classification who underwent definitive radiotherapy. The primary site was the rectum in 3, the duodenum in 1, and the stomach in 30 patients. The radiotherapy dose was 1.5?2.0 Gy (median, 1.5 Gy) and the total dose was 30?40 Gy (median, 30 Gy). The clinical target volume (CTV) was defined as the volume of the entire organ with the lymphoma. Adjacent lymph node areas were not routinely included in the CTV. RESULTS: Complete response (CR) was achieved in all patients. There were no local recurrences, and two cases of recurrence were observed at other sites. The 5-year overall survival rates for non-gastric and gastric MALT lymphomas were 100% and 94.7%, respectively, and the 5-year disease-free survival rates were 100% and 95.7%, respectively. None of the patients died of the current illness. CONCLUSION: Radiotherapy for non-gastric intestinal MALT lymphoma is expected to result in good local control and long-term survival, similar to that for gastric MALT lymphoma.

Lymph Node Metastases Diagnosed by 18F-FDG-PET/CT in Esophageal Squamous Cell Cancer Treated With Concurrent Chemoradiotherapy.

BACKGROUND/AIM: To evaluate whether factors related to the clinical staging of lymph node (LN) metastasis diagnosed by 18F-fluorodeoxyglucose positron-emission tomography/computed tomography (PET/CT) correspond to poor survival in esophageal squamous cell cancer (ESCC) patients treated with concurrent chemoradiotherapy (CCRT). PATIENTS AND METHODS: A total of 69 patients with curative intent and no prior treatment for ESCC or simultaneous treatment for synchronous cancers were investigated. A maximum standardized uptake value (SUVmax) on the highest image pixel in the LN ≥2.5 was considered positive. Location of the involved LN and its impact on survival were analyzed. RESULTS: In the univariate analysis of location, metastasis of the abdominal site, regional abdominal LN, and left gastric LN station negatively affected overall survival (OS) and disease-free survival (DFS). Other adverse clinical factors influencing OS included T4, clinical stage IVA and body mass index <21.2. In terms of DFS, a further unfavorable factor was primary tumor SUVmax ≥10.4. Abdominal site LN metastasis affected both OS and DFS in multivariate analysis. CONCLUSION: LN metastasis diagnosed by PET/CT in abdominal sites was an independent predictor affecting both OS and DFS in ESCC patients who underwent curative CCRT.

Calcium Phosphate Cement Paste Injection as a Fiducial Marker of Cervical Cancer.

BACKGROUND/AIM: Calcium phosphate cement (CPC) is used to fill bone voids in dental, orthopedic, and craniofacial applications. This study evaluated CPC marker as an injectable non-metallic fiducial marker. MATERIALS AND METHODS: Six patients received 3-5 injections of CPC paste placed at a depth of 10 mm into tumors of the cervix before treatment planning CT (TPCT). Patients were treated with external-beam radiotherapy (EBRT) and high-dose rate brachytherapy (BT). We investigated marker visibility on cone-beam CT (CBCT), T2-weighted MRI, and interfraction of the marker motion for cervical cancer patients. RESULTS: Of a total of 22 visible CPC markers at TPCT, 17 CPC markers were visible on the first CBCT. Excluding one patient, all markers were visible on CBCT during EBRT. Of 16 visible CPC markers on CBCT, 13 CPC markers were visible on the magnetic resonance imaging (MRI) obtained before BT. For CPC marker centroid movement, the mean-of-means/systematic variation/random variation were 0.2/0.4/1.4, -1.6/5.1/4.1, and -3.4/2.1/2.8 mm for the left-right, dorsal-ventral, and cranial-caudal directions, respectively. CONCLUSION: This is the first report of a CPC marker injected into tumors of the cervix. It can be visualized on CBCT and MRI with reductions in marker loss and artifacts.

The Importance of Concurrent Chemotherapy for T1 Esophageal Cancer: Role of FDG-PET/CT for Local Control.

AIM: To evaluate whether patients with T1 esophageal squamous cell carcinoma receiving definitive radiotherapy can be managed without concurrent chemotherapy, and the role of 18F-fluorodeoxyglucose positron-emission tomography with computed tomography (FDG-PET/CT) in demonstrating local control (LC). PATIENTS AND METHODS: Twenty-four out of 37 patients with newly-diagnosed T1 EC treated with definitive radiotherapy between July 2009 and July 2016 were retrospectively analyzed. FDG-PET/CT was performed before treatment. Eleven patients were assigned to a concurrent chemoradiotherapy (CRT) group. Thirteen were placed in a no-CRT group. The two groups were compared and univariate analysis of clinical factors influencing the prognosis in each group was conducted. RESULTS: Mean radiotherapy doses were 59.2 Gy in the no-CRT group and 55.5 Gy in the CRT group (p=0.025). Overall survival, disease-free survival, and LC rates at 2 years were lower in the no-CRT group compared to the CRT group. Disease-free survival and LC rates at 2 years were significantly lower in the patients with FDG-avid primary tumor in the no-CRT group (p=0.002 and p=0.002, respectively). All patients with FDG-avid primary tumors in the no-CRT group developed local recurrence. CONCLUSION: It is important to note that all patients with FDG-avid primary tumor in the no-CRT group developed local recurrence. This would suggest that concurrent chemotherapy is an integral part of disease management in patients with T1 esophageal squamous cell carcinoma.

Dosimetric predictors of radiation-induced pericardial effusion in esophageal cancer.

PURPOSE: To evaluate the dose-volume parameters of the pericardium and heart in order to reduce the risk of radiation-induced pericardial effusion (PE) and symptomatic PE (SPE) in esophageal cancer patients treated with concurrent chemoradiotherapy. METHODS: In 86 of 303 esophageal cancer patients, follow-up CT was obtained at least 24 months after concurrent chemoradiotherapy. Correlations between clinical factors, including risk factors for cardiac disease, dosimetric factors, and the incidence of PE and SPE after radiotherapy were analyzed using Cox proportional hazard regression analysis. Significant dosimetric factors with the highest hazard ratios were investigated using zones separated according to their distance from esophagus. RESULTS: PE developed in 49 patients. Univariate analysis showed the mean heart dose, heart V5-V55, mean pericardium dose, and pericardium V5-V50 to all significantly affect the incidence of PE. Additionally, body surface area was correlated with the incidence of PE in multivariate analysis. Grade 3 and 4 SPE developed in 5 patients. The pericardium V50 and pericardium D10 significantly affected the incidence of SPE. The pericardium V50 in patients with SPE ranged from 17.1 to 21.7%. Factors affecting the incidence of SPE were the V50 of the pericardium zones within 3 cm and 4 cm of the esophagus. CONCLUSION: A wide range of radiation doses to the heart and pericardium were related to the incidence of PE. A pericardium V50 ≤ 17% is important to avoid symptomatic PE in esophageal cancer patients treated with concurrent chemoradiotherapy.

Impact of the early detection of esophageal neoplasms in hypopharyngeal cancer patients treated with concurrent chemoradiotherapy.

AIMS: We examined the risk factors and prognostic factors for synchronous esophageal neoplasia (SEN) by comparing the characteristics of hypopharyngeal cancer (HPC) patients with and without SEN. METHODS: We examined 183 patients who were treated with definitive radiotherapy for HPC. Lugol chromoendoscopy screening of the esophagus was performed in all patients before chemoradiotherapy. RESULTS: Thirty-six patients had SEN, 49 patients died of HPC and two died of esophageal cancer. The patients with SEN exhibited significantly higher alcohol consumption than those without SEN (P = 0.018). The 5-year overall survival (OS) rate of the 36 patients with SEN was lower than that of the other patients (36.2% vs 63.4%, P = 0.006). The SEN patients exhibited significantly shorter HPC cause-specific survival than the other patients (P = 0.039). Both the OS (P = 0.005) and the HPC cause-specific survival (P = 0.026) of the patients with SEN were significantly shorter than those of the patients without SEN in multivariate analysis. Category 4/T1 stage esophageal cancer was treated with concurrent chemoradiotherapy (CCRT), endoscopic treatment or chemotherapy. The 5-year survival rates for esophageal cancer recurrence for CCRT, endoscopic treatment and chemotherapy were 71.5, 43.7 and 0%, respectively. The median (range) survival time (months) of CCRT, endoscopic treatment and chemotherapy was 22.7 (7.5-90.6), 46.44 (17.3-136.7) and 7.98 (3.72-22.8), respectively. CONCLUSION: Advanced HPC patients with SEN might have a poorer prognosis than those without SEN even when the esophageal cancer is detected early and managed appropriately.

Symptomatic radiation-induced cardiac disease in long-term survivors of esophageal cancer.

PURPOSE: To evaluate clinical and dosimetric factors retrospectively affecting the risk of symptomatic cardiac disease (SCD) in esophageal cancer patients treated with radiotherapy. PATIENTS AND METHODS: A total of 343 patients with newly diagnosed esophageal cancer were managed with concurrent chemoradiotherapy or radiotherapy alone. Of these, 58 patients were followed at our hospital for at least 4 years. Median clinical follow-up was 79 months. Cardiac toxicity was determined by Common Terminology Criteria for Adverse Events (CTCAE) v. 4.0. The maximum and mean doses to the heart and percentage of the volume were calculated from the dose-volume histograms. RESULTS: SCD manifested in 11 patients. The heart diseases included three pericardial effusions, one pericardial effusion with valvular disease and paroxysmal atrial tachycardia, three atrial fibrillations, one sinus tachycardia, one coronary artery disease, one chest pain with strongly suspected coronary artery disease, and one congestive heart failure. The actual incidence of SCD was 13.8 % at 5 years. Univariate and multivariate analyses of continuous variables revealed that the risk of developing an SCD depended on the volume of the heart receiving a dose greater than 45 Gy (V45), 50 Gy (V50), and 55 Gy (V55). No other clinical factors were found to influence the risk of SCD. For V45, V50, and V55, the lowest significant cutoff values were 15, 10, and 5 %, respectively. CONCLUSION: High-dose and large-volume irradiation of the heart increased the risk of SCD in long-term survivors. Using modern radiotherapy techniques, it is important to minimize the heart dose-volume parameters without reducing the tumor dose.