Dental extraction, intensity-modulated radiotherapy of head and neck cancer, and osteoradionecrosis

Objective To seek evidence for osteoradionecrosis (ORN) after dental extractions before or after intensity-modulated radiotherapy (IMRT) for head and neck cancer (HNC). Methods Medline/PubMed, Embase, and Cochrane Library were searched from 2000 until 2020. Articles on HNC patients treated with IMRT and dental extractions were analyzed by two independent reviewers. The risk ratios (RR) and odds ratios (OR) for ORN related to extractions were calculated using Fisher’s exact test. A one-sample proportion test was used to assess the proportion of pre- versus post-IMRT extractions. Forest plots were used for the pooled RR and OR using a random-effects model. Results Seven of 630 publications with 875 patients were eligible. A total of 437 (49.9%) patients were treated with extractions before and 92 (10.5%) after IMRT. 28 (3.2%) suffered from ORN after IMRT. ORN was associated with extractions in 15 (53.6%) patients, eight related to extractions prior to and seven cases related to extractions after IMRT. The risk and odds for ORN favored pre-IMRT extractions (RR = 0.18, 95% CI: 0.04–0.74, p = 0.031, I2 = 0%, OR = 0.16, 95% CI: 0.03–0.99, p = 0.049, I2 = 0%). However, the prediction interval of the expected range of 95% of true effects included 1 for RR and OR. Conclusion Tooth extraction before IMRT is more common than after IMRT, but dental extractions before compared to extractions after IMRT have not been proven to reduce the incidence of ORN. Extractions of teeth before IMRT have to be balanced with any potential delay in initiating cancer therapy.

Comparison of efficacy and safety between simultaneous integrated boost intensity-modulated radiotherapy and standard-dose intensity-modulated radiotherapy in locally advanced esophageal squamous cell carcinoma: a retrospective study

Objective This study aimed to evaluate the efficacy and safety of simultaneous integrated boost intensity-modulated radiotherapy (SIB-IMRT) versus standard-dose intensity-modulated radiotherapy (SD-IMRT) in the treatment of locally advanced esophageal squamous cell carcinoma. Methods From July 2003 to March 2014, 1748 patients in a single center who received definitive chemoradiotherapy were included in the analysis. A total of 109 patients who underwent SIB-IMRT and fulfilled all inclusion and exclusion criteria were identified as the study group. A total of 266 patients who underwent SD-IMRT (60 Gy/30 fractions, 2 Gy/fraction, 1 time/day, 5 times/week) during the same period were selected as the control group. Propensity score matching (PSM) was used to balance the baseline characteristics. Survival status, treatment failure mode, and the occurrence of adverse events were compared between the two groups. Results There were more women and more cervical and upper thoracic cancers (P = 0.038, < 0.001, respectively) in the SIB-IMRT group before case matching. The median progression-free survival (PFS) in the SD-IMRT and SIB-IMRT groups was 22 and 19 months, respectively, and the median overall survival duration was 24 and 22 months, respectively, with χ2 = 0.244 and P = 0.621. After PSM of 1:1, 138 patients entered the final analysis (69 cases from each group). The median PFS of the SD-IMRT group and the SIB-IMRT group was 13 and 18 months, respectively, with χ2 = 8.776 and P = 0.003. The 1‑, 3‑, and 5‑year overall survival rates were 66.7, 21.7, and 8.7% and 65.2, 36.2, and 27.3%, respectively, and the median overall survival duration was 16 and 22 months, respectively, with χ2 = 5.362 and P = 0.021. Treatment failure mode: 5‑year local regional recurrence rates of SD-IMRT and SIB-IMRT were 50.7 and 36.2%, respectively, with χ2 = 2.949 and P = 0.086. The 5‑year distant metastasis rates of the two groups were 36.2 and 24.6%, respectively, with χ2 = 2.190 and P = 0.139. Adverse events: 3 patients experienced grade 4–5 toxicity (2.2%), including one case of grade 4 radiation esophagitis and two cases of grade 5 radiation pneumonitis, all in the SD-IMRT group; 14 patients experienced grade 3 adverse events (10.1%), primarily including radiation esophagitis, radiation pneumonitis, and hematological toxicity. Conclusion The technique of SIB-IMRT was safe and reliable compared with SD-IMRT. In addition, SIB-IMRT had locoregional control advantages and potential survival benefits.

Dosimetric Risk Factors for Acute Radiation Pneumonitis in Patients With Prior Receipt of Immune Checkpoint Inhibitors

PurposeDosimetric parameters (e.g., mean lung dose (MLD), V20, and V5) can predict radiation pneumonitis (RP). Constraints thereof were formulated before the era of combined immune checkpoint inhibitors (ICIs) and radiotherapy, which could amplify the RP risk. Dosimetric predictors of acute RP (aRP) in the context of ICIs are urgently needed because no data exist thus far.Methods and MaterialsAll included patients underwent thoracic intensity-modulated radiotherapy, previously received ICIs, and followed-up at least once. Logistic regression models examined predictors of aRP (including a priori evaluation of MLD, V20, and V5), and their discriminative capacity was assessed by receiver operating characteristic analysis.ResultsMedian follow-up of the 40 patients was 5.3 months. Cancers were lung (80%) or esophageal (20%). ICIs were PD-1 (85%) or PD-L1 (15%) inhibitors (median 4 cycles). Patients underwent definitive (n=19), consolidative (n=14), or palliative (n=7) radiotherapy; the median equivalent dose in 2 Gy fractions (EQD2) was 60 Gy (IQR, 51.8-64 Gy). Grades 1-5 aRP occurred in 25%, 17.5%, 15%, 2.5%, and 5%, respectively. The only variables associated with any-grade aRP were V20 (p=0.014) and MLD (p=0.026), and only V20 with grade ≥2 aRP (p=0.035). Neither the number of prior ICI cycles nor the delivery of concurrent systemic therapy significantly associated with aRP risk. Graphs were constructed showing the incrementally increasing risk of aRP based on V20 and MLD (continuous variables).ConclusionsThis is the first study illustrating that V20 and MLD may impact aRP in the setting of prior ICIs. However, these data should not be extrapolated to patients without pre-radiotherapy receipt of prior ICIs, or to evaluate the risk of chronic pulmonary effects. If these results are validated by larger studies with more homogeneous populations, the commonly accepted V20/MLD dose constraints could require revision if utilized in the setting of ICIs.

Intensity-Modulated Radiotherapy with Regional Hyperthermia for High-Risk Localized Prostate Carcinoma

Background: The purpose of this study was to evaluate the efficacy and toxicity of adding regional hyperthermia to intensity-modulated radiotherapy (IMRT) plus neoadjuvant androgen deprivation therapy (ADT) for high-risk localized prostate carcinoma. Methods: Data from 121 consecutive patients with high-risk prostate carcinoma who were treated with IMRT were retrospectively analyzed. The total planned dose of IMRT was 76 Gy in 38 fractions for all patients; hyperthermia was used in 70 of 121 patients. Intra-rectal temperatures at the prostate level were measured to evaluate thermal dose. Results: Median number of heating sessions was five and the median total thermal dose of CEM43T90 was 7.5 min. Median follow-up duration was 64 months. Addition of hyperthermia to IMRT predicted better clinical relapse-free survival. Higher thermal dose with CEM43T90 (>7 min) predicted improved biochemical disease-free survival. The occurrence of acute and delayed toxicity ≥Grade 2 was not significantly different between patients with or without hyperthermia. Conclusions: IMRT plus regional hyperthermia represents a promising approach with acceptable toxicity for high-risk localized prostate carcinoma. Further studies are needed to verify the efficacy of this combined treatment.

The impact of the radiotherapy technique in sparing the heart substructures in central tumor irradiation in lung cancer

Introduction: In thoracic radiotherapy (RT), heart sparing is very essential, as the high cardiac dose is associated with poor survival in patients with locally advanced non-small-cell lung cancer (NSCLC). The study aims to determine the doses exposed to heart substructures and coronary arteries by different RT techniques in central tumor irradiation in lung cancer. Methods: Twenty patients with NSCLC, irradiated between January 2018 and December 2020 in our department, were included in this study. Patients whose primary tumor was centrally located in the left lung were selected. The heart substructures [left atrium, right atrium (RA), left ventricle, and right ventricle] and coronary arteries (left main, left anterior descending, circumflex, and right coronary arteries) were delineated by the same physician. The doses of 60 Gy external RT were prescribed in 30 fractions using three-dimensional conformal radiotherapy (3D-CRT), static intensity-modulated radiotherapy (s-IMRT), and dynamic intensity-modulated radiotherapy (d-IMRT) techniques in all patients. The obtaining plans using three different techniques were compared. Results: The d-IMRT plans were statistically the best optimal plan for planning target volume (PTV) [Dmean (p = 0 04), Dmax (p < 0 0001), V95 (p < 0 0001), V107 (p < 0 0001), CI (p < 0 0001) and HI (p < 0 0001)]. The s-IMRT plans were significantly superior to 3D-CRT plans for PTV. RA Dmax and V45 were not different between the three techniques [Dmax (p = 0 148) and V45 (p = 0 12)]. The d-IMRT technique was significantly better in other heart substructures and coronary arteries. Conclusions: Compared to 3D-CRT and s-IMRT techniques, the d-IMRT technique provided the best protection in all heart substructures except for a few parameters (RA Dmax and V45 doses).