Among colorectal cancers (CRCs), high-frequency microsatellite instability (MSI-H) is associated with a better prognosis, compared with low-frequency MSI or microsatellite stability (MSI-L/MSS). ...However, it is unclear whether MSI affects the prognosis of recurrent CRCs.
This study included 2940 patients with stage I-III CRC who underwent complete resection. The associations of MSI status with recurrence patterns, disease-free survival (DFS), overall survival from diagnosis to death (OS1), and overall survival from recurrence to death (OS2) were analysed.
A total of 261 patients (8.9%) had MSI-H CRC. Patients with MSI-H CRC had better DFS, compared to patients with MSI-L/MSS CRC (hazard ratio (HR): 0.619, P<0.001). High-frequency microsatellite instability CRC was associated with more frequent local recurrence (30.0% vs 12.0%, P=0.032) or peritoneal metastasis (40.0% vs 12.3%, P=0.003), and less frequent lung (10.0% vs 42.5%, P=0.004) or liver metastases (15.0% vs 44.7%, P=0.01). Recurrent MSI-H CRC was associated with worse OS1 (HR: 1.363, P=0.035) and OS2 (HR: 2.667, P<0.001). An analysis of patients with colon cancer yielded similar results.
Recurrence patterns differed between MSI-H CRC and MSI-L/MSS CRC, and recurrent MSI-H CRCs had a worse prognosis.
Carbon ion radiotherapy (CIRT) has garnered interest for the treatment of locoregional rectal cancer recurrence. No study has compared CIRT and X-ray radiotherapy (XRT) for reirradiation (reRT) in ...such cases. We analyzed and compared the clinical outcomes such as local control, overall survival, and late toxicity rate between CIRT and XRT, for treating locoregional rectal cancer recurrence. Patients with rectal cancer who received reRT to the pelvis by CIRT or XRT from March 2005 to July 2019 were included. The CIRT treatment schedule was 70.4 Gy (relative biological effectiveness) in 16 fractions. For the XRT group, the median reRT dose was 50 Gy (range 25-62.5 Gy) with a median of 25 fractions (range 3-33). Thirty-five and 31 patients received CIRT and XRT, respectively. Tumour and treatment characteristics such as recurrence location and chemotherapy treatment differed between the two groups. CIRT showed better control of local recurrence (adjusted hazard ratio HR 0.17; p = 0.002), better overall survival (HR 0.30; p = 0.004), and lower severe late toxicity rate (HR 0.15; p = 0.015) than XRT. CIRT was effective for treating locoregional rectal cancer recurrence, with high rates of local control and survival, and a low late severe toxicity rate.
To analyze risk factors and the dose-effect relationship for osteoradionecrosis (ORN) of the mandible after radiotherapy of oral and oropharyngeal cancers.
One-hundred ninety-eight patients with oral ...(45%) and oropharyngeal cancer (55%) who had received external radiotherapy between 1990 and 2000 were retrospectively reviewed. All patients had a dental evaluation before radiotherapy. The median radiation dose was 60 Gy (range, 16-75 Gy), and the median biologically effective dose for late effects (BED(late)) in bone was 114 Gy(2) (range, 30-167 Gy(2)).
The frequency of ORN was 13 patients (6.6%). Among patients with mandibular surgery, eight had ORN at the surgical site. Among patients without mandibular surgery, five patients had ORN on the molar area of the mandible. The median time to ORN was 22 months (range, 1-69 months). Univariate analysis revealed that mandibular surgery and Co-60 were significant risk factors for ORN (p = 0.01 and 0.04, respectively). In multivariate analysis, mandibular surgery was the most important factor (p = 0.001). High radiation doses over BED 102.6 Gy(2) (conventional dose of 54 Gy at 1.8 Gy/fraction) were also a significant factor for ORN (p = 0.008) and showed a positive dose-effect relationship in logistic regression (p = 0.04) for patients who had undergone mandibular surgery.
Mandibular surgery was the most significant risk factor for ORN of mandible in oral and oropharyngeal cancers patients. A BED of 102.6 Gy(2) or higher to the mandible also significantly increases the risk of ORN.
Optimal treatment for locally advanced rectal cancer (LARC) with distant metastasis remains elusive. We aimed to evaluate upfront systemic chemotherapy and short-course radiotherapy (RT) followed by ...delayed surgery for such patients, and to identify favorable prognostic factors.
We retrospectively reviewed 50 LARC patients (cT4 or cT3, <2 mm from the mesorectal fascia) with synchronous metastatic disease. The primary endpoint was progression-free survival (PFS). The secondary endpoints were overall survival, treatment-related toxicity, and compliance. We considered P values <0.05 significant.
At 22 months median follow-up, the median PFS time was 16 months and the 2-year PFS rate was 34.8%. Thirty-five patients who received radical surgery for primary and metastatic tumors were designated the curable group. Six patients with clinical complete response (ypCR) of metastases who underwent radical surgery for only the primary tumor were classified as potentially curable. Nine patients who received no radical surgery (3 received palliative surgery) were deemed the palliative group. The ypCR rate among surgery patients was 13.6%. PFS rates for the curable or potentially curable groups were significantly longer than that of the palliative group (P<0.001). On multivariate analysis, solitary organ metastasis and R0 status were independent prognostic factors for PFS.
These findings demonstrated that a strong possibility that upfront chemotherapy and short-course RT with delayed surgery are an effective alternative treatment for LARC with potentially resectable distant metastasis, owing to achievement of pathologic down-staging, R0 resection, and favorable compliance and toxicity, despite the long treatment duration.
Gastric bleeding negatively impacts the quality of life of patients with unresectable advanced gastric cancer and is frequently lethal. We investigated the efficacy of RT for palliation of gastric ...bleeding from gastric cancer and identified an optimal radiotherapy (RT) strategy.
The study analyzed 57 patients submitted to palliative RT for gastric bleeding associated with gastric cancer between January 2009 and February 2019. Changes in hemoglobin (Hb) levels were analyzed based on measurements taken before and immediately, 1 month, and 2 months after RT. Re-bleeding after RT was identified as either Hb level dropping to < 7.0 g/dL or the administration of a blood transfusion after RT.
The median biologically effective dose (α/β = 10) was 37.5 Gy (range 23.6-58.5). The most common regimen was 25 Gy in five fractions. The mean Hb levels before, immediately after, 1 month, and 2 months after RT (6.6, 9.7, 10.3, and 9.7 g/dL, respectively) were significantly higher than that before RT (all p < 0.001). No significant differences in re-bleeding rates were observed according to total dose, fractional dose, and fraction number. Gastric tumor response evaluated by computed tomography within 2 months after RT showed partial responses were more frequent in patients achieving bleeding control (25.0% vs. 10.8%, p = 0.023) and overall survival was significantly improved for bleeding control within 3 months after RT (median, 15.4 vs. 10.0 weeks, p = 0.048).
RT was an effective modality for gastric bleeding control in gastric cancer, which can be achieved with a short course scheme with five fractions.
Low-dose RT is appropriate for orbital MALToma treatment in terms of high disease control and acceptable morbidity. For reducing toxicity, research on optimized RT dose and target should be ...continued.
Abstract
Objectives
Although mucosa-associated lymphoid tissue lymphoma (MALToma) is sensitive to radiation therapy (RT), the optimal RT dose and treatment volumes have not been established. This study aimed to assess the relapse patterns and outcomes of patients with orbital MALToma who underwent RT and to suggest implications for optimized RT.
Methods
We reviewed 212 patients (246 orbits) diagnosed with orbital MALToma who received RT between 1993 and 2013. Median RT dose was 25.2 Gy. Generally, conjunctival and eyelid lesions were irradiated with electrons, whereas retrobulbar and lacrimal gland lesions with photons. Lens shielding was used for 70% of treated eyes, mainly conjunctival and eyelid tumors.
Results
Relapse occurred in 29 patients. Among 11 patients with local relapse (LR), 4 were attributed to insufficient dose (n = 2) and improper RT volume (n = 2). The 10-year LR, contralateral orbit relapse, and distant relapse rates were 8.6%, 12.8% and 4.9%, respectively. Twelve patients died of disease-specific causes (n = 1) and intercurrent diseases (n = 11). The 10-year relapse-free survival, overall survival, and cause-specific survival rates were 69.7%, 88.2% and 98.8%, respectively. Grade 3 cataracts and nasolacrimal duct obstruction were observed in 27 and 4 orbits, respectively.
Conclusion
Low-dose RT with proper lens shielding is an appropriate treatment for orbital MALToma in terms of high disease control rate and acceptable morbidity. However, lower RT dose may be attempted to further reduce toxicity while maintaining excellent outcomes.
U-Net, based on a deep convolutional network (CNN), has been clinically used to auto-segment normal organs, while still being limited to the planning target volume (PTV) segmentation. This work aims ...to address the problems in two aspects: 1) apply one of the newest network architectures such as vision transformers other than the CNN-based networks, and 2) find an appropriate combination of network hyper-parameters with reference to recently proposed nnU-Net ("no-new-Net"). VT U-Net was adopted for auto-segmenting the whole pelvis prostate PTV as it consisted of fully transformer architecture. The upgraded version (v.2) applied the nnU-Net-like hyper-parameter optimizations, which did not fully cover the transformer-oriented hyper-parameters. Thus, we tried to find a suitable combination of two key hyper-parameters (patch size and embedded dimension) for 140 CT scans throughout 4-fold cross validation. The VT U-Net v.2 with hyper-parameter tuning yielded the highest dice similarity coefficient (DSC) of 82.5 and the lowest 95% Haussdorff distance (HD95) of 3.5 on average among the seven recently proposed deep learning networks. Importantly, the nnU-Net with hyper-parameter optimization achieved competitive performance, although this was based on the convolution layers. The network hyper-parameter tuning was demonstrated to be necessary even for the newly developed architecture of vision transformers.
The study investigated the molecular mechanisms that killed pancreatic cancer cells, including cancer stem cells (CSCs), by carbon ion beam irradiation alone or in combination with miRNA-200c under ...in vitro and in vivo conditions.
Human pancreatic cancer (PC) cells, PANC1 and PK45, were treated with carbon-ion beam irradiation alone or in combination with microRNA-200c (miR-200c) mimic. Cell viability assay, colony and spheroid formation assay, quantitative real-time PCR analysis of apoptosis-, autophagy-, and angiogenesis-related gene expression, xenograft tumor control and histopathological analyses were performed.
The cell viability assay showed that transfection of the miRNA-200c (10 nM) mimic into pancreatic CSC (CD44+/ESA+) and non-CSC (CD44-/ESA-) significantly suppressed proliferation of both types of cell populations described above. Combining carbon-ion beam irradiation with the miRNA-200c mimic significantly reduced the colony as well as spheroid formation abilities compared to that observed with the treatment of carbon-ion beam alone or X-ray irradiation combined with the miRNA-200c mimic. Moreover, the combination of carbon ion beam irradiation and miRNA-200c mimic increased the expression of apoptosis-related gene BAX, autophagy-related genes
and
, addition of gemcitabine (GEM) further enhanced the expression of these genes. In vivo data showed that carbon-ion beam irradiation in combination with the miRNA-200c mimic effectively suppressed xenograft tumor growth and significantly induced tumor necrosis and cavitation.
The combination of miRNA-200c mimic and carbon ion beam irradiation may be powerful radiotherapy that significantly kills pancreatic cancer cells containing CSCs and enhances the effect of carbon-ion beam irradiation compared to carbon-ion beam irradiation alone.
Purpose
This study evaluated the prognostic value of leukocyte, lymphocyte, and neutrophil counts in anal cancer patients undergoing concurrent chemoradiotherapy (CCRT).
Methods
Multi-institutional ...retrospective data review included 148 non-metastatic anal cancer patients treated with definitive CCRT with 5-fluorouracil plus mitomycin C between the year 2001 and 2019. The median radiation dose to the primary tumor was 54 Gy with a median pelvic dose of 45 Gy. Median follow-up duration was 56 months, and complete blood cell counts were analyzed from baseline to 1 year after the completion of radiotherapy.
Results
Although most patients showed a normal number of blood cells before treatment, 6.1% and 4.1% of patients showed leukocytosis (> 10,000/μl) and neutrophilia (> 7500/μl), respectively. After the initiation of treatment, seven patients (4.7%) displayed grade 4 lymphopenia (< 200/μl) at 1 month. Patients with initial leukocytosis showed inferior progression- and locoregional progression-free survival, and neutrophilia was a prognostic factor in all survival outcomes. Grade 4 lymphopenia at 1 month was also significantly associated with overall, progression-, and distant metastasis-free survival. On multivariate analyses, baseline neutrophilia was associated with 56.8-, 22.6-, 10.7-, and 23.0-fold increased risks of death, disease relapse, locoregional progression, and distant metastasis, respectively. Furthermore, lymphocytes < 200/μl at 1 month was linked to 6.8-, 5.4-, and 6.3-fold increased risks for death, disease relapse, and distant metastasis, respectively.
Conclusion
The number of leukocytes, lymphocytes, and neutrophils readily acquired from routine blood tests before and during treatment could be an independent prognostic factor of survival in patients with anal cancer.
Preoperative therapy has gained wide interest in advanced gastric cancer patients due to its potential advantages of improved disease control. Selection of high risk patients based on preoperative ...staging is crucial to choose the candidates for neoadjuvant therapy.
Our institutional review board approved this retrospective study and waived the requirement for patient consent. We searched 394 advanced gastric cancer patients (pT2-4) who underwent curative resection in 2010 without neoadjuvant therapies. Two abdominal radiologists independently reviewed the preoperative CT including tumor depth on CT (CT-tumor depth), which was categorized as follows: intramural, minimal extramural(<1mm), spiculated extramural(≥1mm) and nodular extramural infiltration. The impact of clinicoradiologic factors on disease recurrence and disease free survival (DFS) was evaluated. Recursive partitioning analysis was performed to suggest prediction models for recurrence.
Of total 394 patients, 86 patients (21.8%) experienced recurrence. Spiculated (≥1mm) and nodular extramural tumor infiltration and CT size of 5-10cm were independent predictors of disease recurrence and significantly associated with worse DFS. Lymph node involvement on CT was not significantly associated with patient outcome. Among patients with same pT4a stage, the recurrence rate rises and DFS gets worse as the extramural tumor infiltration progresses (P < 0.001). The prediction model for recurrence revealed that size and CT-tumor depth were the two major discriminating factors.
CT-tumor depth and size could be used as independent predictors for prognosis. Preoperative CT can be used for prognostic stratification to select high risk patients for whom neoadjuvant therapies might be considered.
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