Salivary metabolites as novel independent predictors of radiation pneumonitis.

PURPOSE: Radiotherapy is an integral treatment for non-small cell lung cancer (NSCLC); however, radiation-induced toxicities such as radiation pneumonitis (RP) present a considerable challenge. Herein, we aimed to evaluate the potential of salivary metabolomics as an independent risk factor for predicting RP. METHODS: This study included 62 consecutive patients with NSCLC who underwent thoracic radiotherapy at Tokyo Medical University between September 2016 and December 2018. The median age of the patients was 75 years (range: 41-89), comprising 47 (75.8%) males and 15 (24.2%) females. Patients with stage I NSCLC received 75 Gy in 30 fractions, whereas those with stage II and III NSCLC received 66 Gy in 33 fractions. Saliva samples were collected before treatment and at 2 weeks, 1 month, 3 months, and 1 year after initiating radiotherapy. Clinical RP was defined as grade 2 according to the Common Toxicity Criteria for Adverse Events. Salivary metabolomics were analyzed using capillary electrophoresis-mass spectrometry. Salivary metabolites were evaluated as potential predictors of RP. RESULTS: Clinical RP was observed in 11 patients (17.7%); no RP-related deaths were observed. Clinical RP developed at a median of 4 months (range: 2-6 months) after initiating radiotherapy. Three metabolites, butyrate, propionate, and hexanoate, collected before radiotherapy exhibited predictive ability for clinical RP. Multivariate logistic analysis indicated butyrate (P = 0.033) as a predictive factor, along with the previously known factor of lung volume irradiated with > 20 Gy (P = 0.045). CONCLUSION: Salivary metabolite butyrate was an independent risk factor for clinical RP.

Predicting factors for primary cervical cancer recurrence after definitive radiation therapy.

OBJECTIVES: The study aimed to retrospectively investigate the apparent diffusion coefficient (ADC) of primary cervical cancer to examine the recurrence correlations in patients treated with radiotherapy (RT). METHODS: The ADC of 31 patients with cervical cancer treated with RT were analyzed as possible risk factors for recurrence. A receiver operating characteristic (ROC) curve of the mean ADC (ADCmean) for the recurrence was generated to determine the cut-off value that yielded optimal sensitivity and specificity. The patient population was subdivided according to the risk factors for recurrence, and the disease-free survival (DFS) was analyzed. The following were investigated to explore the risk factors for recurrence: age, performance status, stage, pelvic lymph node metastasis, histologic tumor grade, maximal diameter of the primary tumor, chemotherapy, and ADCmean. RESULTS: The median follow-up duration of the patients was 25 months. The recurrence was recognized in 9 (29%) of the 31 cases. The ROC analysis of recurrence showed that the area under the ADCmean curve was 0.889 (95% CI, 0.771-1.000; p = 0.001). The cut-off value of ADC mean was 0.900 × 10- 3 mm2/s, with a sensitivity of 86.4% and a specificity of 88.9%. By univariate analysis, the ADCmean was the only factor significantly associated with recurrence. CONCLUSION: The ADCmean of the primary tumor is a potential predictive factor for the recurrence in of cervical cancer. ADVANCES IN KNOWLEDGE: The ADCmean of the primary tumor is a predictor of recurrence in patients with pre-treatment cervical cancer evaluation.

Evaluation of the relationship between the range of radiation-induced lung injury on CT images after IMRT for stage I lung cancer and dosimetric parameters.

BACKGROUND: This study evaluated the correlation between radiation-induced lung injury (RILI) and dosimetric parameters on computed tomography (CT) images of stage I non-small cell lung cancer (NSCLC) patients undergoing intensity-modulated radiotherapy (IMRT). MATERIALS AND METHODS: Sixty-three stage I NSLC patients who underwent IMRT were enrolled in the study. The patients underwent CT within 6 months (acute phase) and 1.5 years (late phase) after radiotherapy. These were fused with the planned irradiation CT. The range of RILI was measured from 10% to 100%, with an IC in 10% increments. RESULTS: The median interval from completion of radiotherapy to acute and late phase CT was 92 and 440 days, respectively. The median RILI ranges of the acute and late phases were in the 80% (20-100%) and 70% dose regions (20-100%), respectively. The significantly narrower range of RILI when lung V20 in the acute phase was less than 19.2% and that of V5 in the late phase was less than 27.6% at the time of treatment planning. CONCLUSIONS: This study showed that RILI occurred in a localized range in stage I NSCLC patients who underwent IMRT. The range of RILI was correlated with V20 in the acute phase and V5 in the late phase. KEY MESSAGES RILI correlated with V20 in acute and V5 in late phase. The shadow of RILI occurred in 80% dose region in acute and 70% in late phase. No relationship exists between radiographic changes in RILI and PTV volume.

Predictive factors for local control of early glottic squamous cell carcinomas after definitive radiotherapy.

The aim of the present study was to retrospectively investigate the risk factors of local failure for T1 glottic carcinoma irradiated with a prescription dose of 66 Gy. Between July 2006 and December 2017, 64 patients with T1 glottic squamous cell carcinoma treated with 66 Gy/33 fractions were analyzed for risk factors of local failure. The sex, age, performance status, T stage, overall treatment time, anterior commissure involvement, smoking status during/after treatment, histological tumor grade and pretreatment hemoglobin level were investigated. The maximum, mean and minimum doses, and the homogeneity index for the glottic larynx were calculated for dosimetric risk factors of local failure. The median follow-up duration was 51 months. Local failure was observed in 6 patients (9.5%). Among all risk factors, only the minimum dose to the glottic larynx was found to be significantly associated with local failure (P=0.025). The 5-year local control rates for a minimum dose to the glottic larynx of <65 and ≥65 Gy were 79 and 95%, respectively, with a statistically significant difference (P=0.015). No patients exhibited grade ≥3 late adverse effects. The minimum dose to the glottic larynx was the only factor significantly associated with local failure. Thus, local control of T1 glottic carcinoma may improve with a minimum dose of ≥65 Gy to the glottic larynx. In conclusion, radiotherapy with a minimum prescription dose of ≥65 Gy to the glottic larynx appears to be safe and achieves a high local control rate for T1 glottic carcinoma.

Prognostic impact of solid tumor component diameter in early-stage non-small cell lung carcinoma treated with intensity-modulated fractionated radiotherapy: a retrospective analysis impact of solid tumor component diameter in NSCLC treated with IMRT.

OBJECTIVE: To investigate the suitability of the new diameter-based subgroupings of the eighth edition Tumor Node Metastasis (TNM) classification system regarding radiotherapy treatment for early-stage non-small-cell lung cancer (NSCLC), we retrospectively re-analyzed the clinical data of patients treated with intensity-modulated radiotherapy using non-coplanar beams (ncIMRT) for Stage I NSCLC. METHODS: Between March 2011 and March 2018, 92 patients with 94 tumors who were diagnosed with Stage I NSCLC according to the seventh edition TNM classification system were enrolled and underwent ncIMRT of 75 Gy in 30 fractions. Local control (LC), progression-free survival (PFS), and overall survival (OS) were retrospectively investigated according to the T-classification subdivisions of the eighth edition and maximal solid tumor component diameter. RESULTS: The median follow-up period was 32.5 months. The median maximum tumor and solid tumor component diameters were 22 mm and 18 mm, respectively. 3-year LC, PFS, and OS rates were 84.1%, 69.4%, and 85.3%, respectively. The 3-year LC rates were 91.0 and 76.8% in the groups with tumor diameter ≤2 cm and >2 cm, corresponding to the T1c and T1b subdivisions of the eighth edition, respectively (p = 0.24). In the ≤2 cm and >2 cm solid tumor component groups, the 3 year LC rates were 93.6 and 63.2%, respectively, which were significantly different (p = 0.007). CONCLUSION: LC rates after radiotherapy in patients with Stage I NSCLC were correlated with solid tumor component diameter. High LC rates in patients with solid tumor components <2 cm in diameter were associated with high PFS and OS rates. ADVANCES IN KNOWLEDGE: This study suggests that the eighth edition TNM classification system, which focuses on solid tumor components rather than tumor diameter, can be applied to radiotherapy.

Phase II study of compensator-based non-coplanar intensity-modulated radiotherapy for Stage I non-small-cell lung cancer.

We conducted a Phase II study to evaluate the usefulness of compensator-based non-coplanar intensity-modulated radiotherapy (ncIMRT) for patients with surgically inaccessible Stage I non-small-cell lung cancer (NSCLC). Patients with pathologically proven or clinically diagnosed surgically inaccessible Stage I NSCLC were enrolled in this study from May 2011 to April 2014. These patients underwent ncIMRT of 75 Gy in 30 fractions regardless of the tumor location. The primary end point was 3-year overall survival, and the secondary end points were local control rate and treatment-related toxicities. A total of 48 patients (50 tumors) were enrolled in this study. Of the 50 tumors, the Stage T1 to T2 ratio was 31 to 19, and the ratio of tumors located in the central to peripheral areas was 11 to 39. During the median follow-up time of 35.9 months, the 3-year actuarial local progression-free and overall survival rates were 82.6% and 87.1%, respectively. No patients experienced toxicities of Grade 3 or greater. Standard-fractionated ncIMRT was effective and safe for patients with surgically inaccessible stage I NSCLC, regardless of the tumor location.

Predicting risk factors for radiation pneumonitis after stereotactic body radiation therapy for primary or metastatic lung tumours.

OBJECTIVE: To investigate risk factors for radiation-induced pneumonitis (RP) after hypofractionated stereotactic body radiotherapy (SBRT) in patients with lung tumours. METHODS: From May 2004 to January 2016, 66 patients with 71 primary or metastatic lung tumours were treated with SBRT; these 71 cases were retrospectively analyzed for RP. To explore the risk factors for RP, the following factors were investigated: age, sex, performance status, operability, number of treatments, respiratory gating, pulmonary emphysema, tumour location and subclinical interstitial lung disease (ILD). Irradiated underlying lung volumes of more than 5 Gy, 10 Gy, 20 Gy and 30 Gy (Lung V5, V10, V20 and V30), mean lung dose and volumes of gross tumour volume (in cubic centimetre) and planning target volume were calculated for possible risk factors of RP. RESULTS: The median follow-up period was 32 months. RP of Grade 2 or more, according to the Common Terminology Criteria for Adverse Events v. 4.0, was detected in 6 (8.4%) of the 71 cases. Grade 5 RP was identified in two cases. Of the risk factors of RP, subclinical ILD was the only factor significantly associated with the occurrence of RP of Grade 2 or more (p < 0.001). Both cases with Grade 5 RP had ILD with a honeycombing image. CONCLUSION: Subclinical ILD was the only significant factor for Grade 2-5 RP. In addition, the cases with honeycombing had a high potential for fatality related to severe RP. Patients with subclinical ILD should be carefully monitored for the occurrence of severe RP after SBRT. Advances in knowledge: Hypofractionated SBRT for primary or metastatic lung tumours provides a high local control rate and safe treatment.

Impact of the duration of hormonal therapy following radiotherapy for localized prostate cancer.

External-beam radiotherapy (EBRT) combined with androgen deprivation therapy (ADT) is known to provide improved survival outcomes compared with EBRT alone in the treatment of prostate cancer; however, the use of ADT has been reported to be associated with adverse events. Accordingly, the aim of the present study was to clarify the adequate duration of ADT when combined with EBRT to treat patients with high-risk localized prostate cancer, with consideration of survival outcomes and toxicity. Between 2001 and 2011, 173 patients with high-risk localized prostate cancer received ADT combined with EBRT, at a median dose of 69.6 Gy. Of these, 54 (31%) underwent short-term ADT (<36 months) and 119 (69%) underwent long-term ADT (≥36 months). During the median follow-up period of 54 months, the five-year progression-free survival rate of patients receiving short-term ADT (72.9%) was significantly lower than that of patients receiving long-term ADT (92.8%) (P<0.01). Furthermore, the incidence of cardiovascular toxicity at grade II or above was significantly higher amongst patients treated with short-term ADT compared with patients treated with long-term ADT (P<0.01). Thus, the present study determined that ADT for ≥36 months combined with EBRT significantly improved the progression-free survival of patients with high-risk localized prostate cancer and exhibited an acceptable toxicity profile.