Radiation Oncology Journal最新文献

Purpose: The purpose of this study was to determine if somatic mutations are associated with clinical and pathologic outcomes in patients with borderline resectable pancreatic cancer (BRPC) or locally advanced pancreatic cancer (LAPC) who were treated with neoadjuvant chemotherapy and stereotactic body radiotherapy (SBRT).

Materials and methods: Patients treated with neoadjuvant chemotherapy and SBRT followed by surgical resection from August 2016 to January 2019 and who underwent next generation sequencing of their primary tumor were included in the study. Next-generation sequencing was performed either in-house with a Solid Tumor Panel or with FoundationOne CDx. Univariate (UVA) and multivariable analyses (MVA) were performed to determine associations between somatic mutations and pathologic and clinical outcomes.

Results: Thirty-five patients were included in the study. Chemotherapy consisted of modified FOLFIRINOX, gemcitabine and nab-paclitaxel, or gemcitabine and capecitabine. Patients were treated with SBRT in 33 Gy in 5 fractions. On UVA and MVA, tumors with KRAS G12V mutation demonstrated better pathologic tumor regression grade (TRG) to neoadjuvant therapy when compared to tumors with other KRAS mutations (odds ratio = 0.087; 95% confidence interval [CI], 0.009-0.860; p = 0.036). On UVA and MVA, mutations in NOTCH1/2 were associated with worse overall survival (hazard ratio [HR] = 4.15; 95% CI, 1.57-10.95; p = 0.004) and progression-free survival (HR = 3.61; 95% CI, 1.41-9.28; p = 0.008). On UVA, only mutations in NOTCH1/2 were associated with inferior distant metastasis-free survival (HR = 3.38; 95% CI, 1.25-9.16; p = 0.017).

Conclusion: In BRPC and LAPC, the KRAS G12V mutation was associated with better TRG following chemotherapy and SBRT. Additionally, NOTCH1/2 mutations were associated with worse overall survival, distant metastasis-free survival, and progression-free survival.

Purpose: Radiotherapy is essential for the treatment of breast cancer (BC). However, adverse effects may occur in healthy tissue, during treatment and even after several months. Although it is known that this clinical radiosensitivity is multifactorial, the factors involved are unknown yet. In this study, we evaluated the effect of these factors on the development of radiodermatitis in patients undergoing radiotherapy.

Materials and methods: Demographic and lifestyle data collected during face-to-face interviews of 122 BC patients and data from clinical records were investigated. Most patients underwent conventional three-dimensional radiotherapy treatment. A total dose of 50 Gy was administered (2 Gy/day), followed by a boost in a tumor bed with a total dose of 18 Gy (2 Gy/day). Radiotoxicity was evaluated weekly using the Radiation Therapy Oncology Group classification system (range, 0 to 4, according to the severity).

Results: In the present study, 75.4% of patients presented acute skin toxic effects with different degrees of severity. In 25% of cases, these effects manifested at the end of the fourth week at a cumulative dose of 40 Gy. The association of grade ≥2 acute skin reactions with body mass index (BMI) and breast size and between grade 3-4 and age was positive compared with controls. However, the role of the other factors could not be confirmed.

Conclusion: Analysis of the factors related to individual radiosensitivity suggests that age, BMI and breast size play an important role in the development of acute skin toxicity during treatment. Particular attention to patients who present these characteristics would help to control treatment effectiveness and therefore optimize their quality of life.

Purpose: Although the conventional gamma ray brachytherapy has been successful in treating endometrioid endometrial adenocarcinoma (EC), the molecular and cellular mechanisms of this anti-tumorigenic response remain unclear. Therefore, we investigated whether gamma ray irradiation induces changes in the number of FoxP3+ T-regulatory lymphocytes (Tregs), CD56+ natural killer cells (NK), and the expression of progesterone receptor membrane component 1 (PGRMC1) in the tumor microenvironment (TME).

Materials and methods: According to the inclusion criteria, 127 cases were selected and grouped into irradiation-treated (Rad+) and control (underwent surgery) groups and analyzed using immunohistochemistry. Predictive prognostic values were analyzed using Mann-Whitney U test, ROC analysis, relative risk, log-rank, Spearman rank tests and multivariate Cox's regression.

Results: We observed significant differences (p < 0.001) between the radiation-treated patients and the control groups in FoxP3+ Tregs numbers, CD56+ NK cells and PGRMC1 expression. Gamma ray induced a 3.71- and 3.39-fold increase in the infiltration of FoxP3+ cells, CD56+ NK cells, respectively and 0.0034-fold change in PGRMC1 expression. Univariate and multivariate analyses revealed predictive role of the parameters. In the irradiated patients' group, inverted correlations between clinical unfavorable outcome, FoxP3+ Tregs and CD56+ NK cells were observed.

Conclusion: Our results suggest an immune-modulating role, specifically by increasing immune cell infiltration, of gamma radiation in the TME which may potentially be utilized as biomarkers in prognostic values.

Purpose: To investigate the efficacy and safety of intensity-modulated radiotherapy (IMRT)-based re-irradiation (reRT) for recurrent or second primary head and neck cancer (HNC).

Materials and methods: Patients who underwent IMRT-based reRT for recurrent or second primary HNC between 2007 and 2019 at two institutions were included. Medical records and dosimetric data were retrospectively reviewed. Overall survival (OS), progression-free survival (PFS), severe late toxicities, and clinicopathological prognostic factors were analyzed.

Results: A total of 42 patients were analyzed. With a median follow-up of 15.1 months (range, 3.7 to 85.8 months), the median OS was 28.9 months with a 2-year OS rate of 54.6%. The median PFS and 2-year PFS rates were 10.0 months and 30.9%, respectively. Multivariate analysis showed that good performance (Eastern Cooperative Oncology Group [ECOG] 0 or 1), a longer time interval (≥24 months) between radiotherapy courses, and higher reRT dose (>60 Gy) were significantly favorable factors for OS (all p < 0.05). Higher reRT dose and salvage surgery were significantly associated with improved PFS (all p < 0.05). Regarding the Multi-Institution Reirradiation (MIRI) Collaborative RPA classification, the 2-year OS rates of each class were 87.5% in class I, 51.8% in class II, and 0% in class III (p = 0.008). Grade ≥3 late toxicity was reported in 10 (23.8%) patients. There was no significant factor associated with increased late toxicities.

Conclusion: IMRT-based reRT should be considered as a treatment option for patients with recurrent or second primary HNC. Further trials are needed to establish a subset of patients who may benefit from reRT without severe late toxicity.

Purpose: To evaluate the prognostic value of the pretreatment maximum standardized uptake value (SUVmax) for locoregional control (LRC) of early glottic cancer treated with primary radiotherapy.

Materials and methods: We retrospectively reviewed the medical records of 101 patients with T1-T2N0 glottic cancer treated with helical tomotherapy between 2013 and 2016. The clinical T-stages were T1 in 87 (86.1%) and T2 in 14 (13.9%) patients. The median total dose was 63 Gy (63-67.5 Gy) in 2.25 Gy per fraction. The survival outcomes were plotted using Kaplan-Meier curves. Receiver operating characteristic curves were used to assess the optimal SUVmax cut-off value for predicting locoregional recurrence.

Results: The median follow-up period was 58 months (range, 11 to 90 months). The 5-year overall survival (OS) and locoregional recurrence-free survival rates were 96.8% and 85.4%, respectively. The median pretreatment SUVmax of the primary tumor for all 101 patients was 2.3 (range, 1.1 to 9.1). The best cut-off value for SUVmax for predicting LRC was 3.3, with a sensitivity of 78.6% and specificity of 73.6%. Univariate analysis showed that T-stage, overall treatment time (≥43 days), and high SUVmax (≥3.3) were significant predictors of LRC. Multivariate analysis showed that LRC was independently affected by a high SUVmax (≥3.3) (hazard ratio = 5.505, p = 0.020).

Conclusion: High pretreatment SUVmax (≥3.3) is a negative prognostic factor for LRC in early glottic cancer patients treated with primary radiotherapy.

This review is devoted to a rare in clinical practice, but promising phenomenon of regression distant non-irradiated metastases in combination therapy of cancer patients. R. H. Mole in 1953 suggested introducing the term "abscopal effect" to denote the effect of ionizing radiation "at a distance from the irradiated volume but within the same organism." Currently, it is a hypothesis in the treatment of metastatic cancer, when there is a regression of untreated areas simultaneously with a decrease in the tumor. After the discovery of immune checkpoint cases were increase with patients treated with check-point blockade (especially lymphocyte associated protein 4, programmed cell death 1/programmed cell death 1 ligand 1) and which have an abscopal effect. This review systematizes works covering the time period from 1969 to 2019, which give cases of the abscopal effect at different localizations. However, abscopal effect is a poorly understood phenomenon. In this review, the authors tried to collect all information about the possible mechanisms of the abscopal effect, possible role in antitumor response and frequency abscopal effect at radio/immunotherapy or combined both.

Purpose: This study was performed to investigate the efficacy and safety of short-course radiation therapy (SCRT) and sequential chemotherapy followed by delayed surgery in locally advancer rectal cancer with subgroup analysis between the older and young patients.

Materials and methods: In this single-arm phase II clinical trial, eligible patients with locally advanced rectal cancer (T3-4 and/or N1-2) were enrolled. All the patients received a median three sequential cycles of neoadjuvant CAPEOX (capecitabine + oxaliplatin) chemotherapy. A total dose of 25 Gy in five fractions during 1 week was prescribed to the gross tumor and regional lymph nodes. Surgery was performed about 8 weeks following radiotherapy. Pathologic complete response rate (pCR) and grade 3-4 toxicity were compared between older patients (≥65 years) and younger patients (<65 years).

Results: Ninety-six patients with locally advanced rectal cancer were enrolled. There were 32 older patients and 64 younger patients. Overall pCR was 20.8% for all the patients. Older patients achieved similar pCR rate (18.7% vs. 21.8; p = 0.795) compared to younger patients. There was no statistically significance in terms of the tumor and the node downstaging or treatment-related toxicity between older patients and younger ones; however, the rate of sphincter-saving surgery was significantly more frequent in younger patients (73% vs. 53%; p=0.047) compared to older ones. All treatment-related toxicities were manageable and tolerable among older patients.

Conclusion: Neoadjuvant SCRT and sequential chemotherapy followed by delayed surgery was safe and effective in older patients compared to young patients with locally advanced rectal cancer.

Purpose: Radiomic models elaborate geometric and texture features of tumors extracted from imaging to develop predictors for clinical outcomes. Stereotactic body radiation therapy (SBRT) has been increasingly applied in the ablative treatment of thoracic tumors. This study aims to identify predictors of treatment responses in patients affected by early stage non-small cell lung cancer (NSCLC) or pulmonary oligo-metastases treated with SBRT and to develop an accurate machine learning model to predict radiological response to SBRT.

Materials and methods: Computed tomography (CT) images of 85 tumors (stage I-II NSCLC and pulmonary oligo-metastases) from 69 patients treated with SBRT were analyzed. Gross tumor volumes (GTV) were contoured on CT images. Patients that achieved complete response (CR) or partial response (PR) were defined as responders. One hundred ten radiomic features were extracted using PyRadiomics module based on the GTV. The association of features with response to SBRT was evaluated. A model using support vector machine (SVM) was then trained to predict response based solely on the extracted radiomics features. Receiver operating characteristic curves were constructed to evaluate model performance of the identified radiomic predictors.

Results: Sixty-nine patients receiving thoracic SBRT from 2008 to 2018 were retrospectively enrolled. Skewness and root mean squared were identified as radiomic predictors of response to SBRT. The SVM machine learning model developed had an accuracy of 74.8%. The area under curves for CR, PR, and non-responder prediction were 0.86 (95% confidence interval [CI], 0.794-0.921), 0.946 (95% CI, 0.873-0.978), and 0.857 (95% CI, 0.789-0.915), respectively.

Conclusion: Radiomic analysis of pre-treatment CT scan is a promising tool that can predict tumor response to SBRT.

Purpose: Re-irradiation is a treatment option for recurrent esophageal cancer patients with a history of radiotherapy, but there is a risk of severe late adverse effects. This study focused on the efficacy and safety of re-irradiation using hyperfractionated radiotherapy.

Materials and methods: Twenty-six patients who underwent re-irradiation by the hyperfraction technique using twice-daily irradiation of 1.2 Gy per fraction for recurrent esophageal cancer were retrospectively included in this study. The overall survival period after the start of secondary radiotherapy and the occurrence of late adverse effects were investigated.

Results: Of 26 patients, 21 (81%) received re-irradiation with definitive intention and 21 (81%) underwent concurrent chemotherapy. The median re-irradiation dose was 60 Gy in 50 fractions in 25 treatment days, and the median accumulated irradiation dose in equivalent dose in 2 Gy per fraction was 85.4 Gy with an α/β value of 3. The median interval between two courses of radiotherapy was 21.0 months. The median overall survival period was 15.8 months and the 1-year and 3-year overall survival rates were 64.3% and 28.3%, respectively. Higher dose of re-irradiation and concurrent chemotherapy significantly improved survival (p < 0.001 and p = 0.019, respectively). Severe late adverse effects with the Common Terminology Criteria for Adverse Events grade 3 or higher were observed in 5 (19.2%) patients, and 2 (7.7%) of them developed a grade 5 late adverse effect.

Conclusion: High-dose re-irradiation using a hyperfractionated schedule with concurrent chemotherapy might be related to good prognosis, while the rate of late severe adverse effects is not high compared with the rates in past reports.

Purpose: Pulmonary large cell neuroendocrine carcinoma (LCNEC) is a high-grade lung neuroendocrine tumor with a poor prognosis, similar to small cell lung cancer (SCLC). However, it remains unclear whether to treat LCNEC as non-small-cell lung cancer (NSCLC) or as SCLC. We reviewed our experiences to suggest appropriate treatment strategy for resected pulmonary LCNEC.

Materials and methods: Forty-four patients were treated for pathologically diagnosed pulmonary LCNEC during 2005‒2018. We considered curative surgery first in early-stage or some locally advanced tumors, unless medically inoperable. Adjuvant treatments were decided considering patient's clinical and pathological features. After excluding two stage I tumors with radiotherapy alone and three stage III tumors with upfront chemotherapy, we analyzed 39 patients with stage I‒III pulmonary LCNEC, who underwent curative resection first.

Results: Adjuvant chemotherapy (NSCLC-based 91%, SCLC-based 9%) was performed in 62%, and adjuvant radiotherapy was done in three patients for pN2 or positive margin. None received prophylactic cranial irradiation (PCI). With a median follow-up of 30 months, the 2- and 5-year overall survival (OS) rates were 68% and 51%, and the 2- and 5-year recurrence-free survival (RFS) rates were 49% and 43%, respectively. Aged ≥67 years and SCLC-mixed pathology were significant poor prognostic factors for OS or RFS (p < 0.05). Among 17 recurrences, regional failures were most common (n = 6), and there were five brain metastases.

Conclusions: Surgery and adjuvant treatment (without PCI) could achieve favorable outcomes in pulmonary LCNEC, which was more similar to NSCLC, although some factors worsened the prognosis. The importance of intensified adjuvant therapies with multidisciplinary approach remains high.