Feng-Ming Hsu

Using Cone-Beam Computed Tomography to Evaluate the Impact of Bladder Filling Status on Target Position in Prostate Radiotherapy

Purpose:To assess bladder filling status and its impact on target position during daily intensity-modulated radiation therapy (IMRT) using cone-beam computed tomography (CBCT) in prostate cancer patients.Patients and Methods:23 patients with prostate cancer undergoing image-guided IMRT (78 Gy in 39 fractions) were included. On-board CBCT images were acquired daily and an endorectal balloon was placed daily. All patients were instructed to have a full bladder. The interfraction changes in bladder dimensions in left-right (LR), anterior-posterior (AP), and superior-inferior (SI) directions were measured from CBCT images. Distances from the uppermost part of prostate to pubic bone (PP) and from the uppermost part of prostate to treatment isocenter (PI) were measured to determine changes in target position. Standard deviation (SD) in all fractions of each patient was used to compare the variations between patients. Bladder dimension change ratio and Z-score were used to normalize data between patients.Results:A total of 867 CBCT images were evaluated. The average LR, AP, and SI bladder dimensions were 7.8 ± 1.5 cm, 6.7 ± 1.4 cm, and 5.6 ± 1.7 cm, respectively. The average LR, AP, and SI bladder dimension change ratios were 0.88 ± 0.17, 0.90 ± 0.15, and 0.86 ± 0.32, respectively. The SD was significantly greater in SI dimension than in LR (p < 0.001) and AP (p < 0.001) dimensions. The interfraction changes in the three bladder dimensions were significantly larger than those of target position, and did not correlate with target position changes.Conclusion:Though they were not negligible, changes in bladder filling status did not have a significant impact on target position.Ziel:Beurteilung des Blasenfüllungszustands und seines Einflusses auf die Zielposition bei der täglichen intensitätsmodulierten Radiotherapie (IMRT) unter Einsatz der Cone-Beam-Computertomographie (CBCT) bei Patienten mit Prostatakarzinom.Patienten und Methodik:Es wurden 23 Patienten mit Prostatakarzinom erfasst, die mit bildgesteuerter IMRT (78 Gy verteilt auf 39 Fraktionen) behandelt wurden. Täglich wurden On-Board-CBCT-Bilder aufgenommen und ein endorektaler Ballonkatheter eingesetzt. Alle Patienten wurden angewiesen, mit voller Blase zu erscheinen. Anhand der CBCT-Bilder wurden Änderungen der Blasenausdehnung von Fraktion zu Fraktion in Links-rechts-(LR-), Anterior-posterior-(AP-) und Superior-inferior-(SI-)Richtung gemessen. Um Änderungen der Zielposition zu ermitteln, wurde jeweils der Abstand vom obersten Punkt der Prostata zum Schambein (PP) und vom obersten Punkt der Prostata zum Bestrahlungsisozentrum (PI) gemessen. Die Standardabweichung (SD) bei allen Fraktionen der Patienten wurde verwendet, um die Variationen zwischen Patienten zu vergleichen. Der Änderungsquotient der Blasenausdehnung und der Z-Wert wurden verwendet, um Daten zwischen den Patienten zu normalisieren.Ergebnisse:Insgesamt wurden 867 CBCT-Bilder ausgewertet. Die durchschnittliche LR-, AP- bzw. SI-Blasenausdehnung betrug 7,8 ± 1,5 cm, 6,7 ± 1,4 cm bzw. 5,6 ± 1,7 cm. Der durchschnittliche Änderungsquotient der LR-, AP- bzw. SI-Blasenausdehnung lag bei 0,88 ± 0,17, 0,90 ± 0,15 bzw. 0,86 ± 0.32. Die SD war bei der SI-Ausdehnung signifikant größer als bei der LR- (p < 0,001) und der AP-Ausdehnung (p < 0,001). Die Änderungen der drei Parameter für die Blasenausdehnung von Fraktion zu Fraktion waren signifikant größer als jene der Zielposition und korrelierten nicht mit Änderungen der Zielposition.Schlussfolgerung:Änderungen im Blasenfüllungszustand hatten, obwohl sie nicht zu vernachlässigen waren, keine signifikanten Auswirkungen auf die Zielposition.

Improved local control by surgery and paclitaxel-based chemoradiation for esophageal squamous cell carcinoma: Results of a retrospective non-randomized study†

To investigate the impact of using paclitaxel in chemoradiation on locally advanced esophageal squamous cell carcinoma (SCC) treated with or without surgery.

Retrospective Analysis of Outcome Differences in Preoperative Concurrent Chemoradiation With or Without Elective Nodal Irradiation for Esophageal Squamous Cell Carcinoma

PURPOSE To evaluate the efficacy and patterns of failure of elective nodal irradiation (ENI) in patients with esophageal squamous cell carcinoma (SCC) undergoing preoperative concurrent chemoradiation (CCRT) followed by radical surgery. METHODS AND MATERIALS We retrospectively studied 118 patients with AJCC Stage II to III esophageal SCC undergoing preoperative CCRT (median, 36 Gy), followed by radical esophagectomy. Of them, 73 patients (62%) had ENI and 45 patients (38%) had no ENI. Patients with ENI received radiotherapy to either supraclavicular (n = 54) or celiac (n = 19) lymphatics. Fifty-six patients (57%) received chemotherapy with paclitaxel plus cisplatin. The 3-year progression-free survival, overall survival, and patterns of failure were analyzed. Distant nodal recurrence was classified into M1a and M1b regions. A separate analysis using matched cases was conducted. RESULTS The median follow-up was 38 months. There were no differences in pathological complete response rate (p = 0.12), perioperative mortality rate (p = 0.48), or delayed Grade 3 or greater cardiopulmonary toxicities (p = 0.44), between the groups. More patients in the non-ENI group had M1a failure than in the ENI group, with 3-year rates of 11% and 3%, respectively (p = 0.05). However, the 3-year isolated distant nodal (M1a + M1b) failure rates were not different (ENI, 10%; non-ENI, 14%; p = 0.29). In multivariate analysis, pathological nodal status was the only independent prognostic factor associated with overall survival (hazard ratio = 1.78, p = 0.045). The 3-year overall survival and progression-free survival were 45% and 45%, respectively, in the ENI group, and 52% and 43%, respectively, in the non-ENI group (p = 0.31 and 0.89, respectively). Matched cases analysis did not show a statistical difference in outcomes between the groups. CONCLUSIONS ENI reduced the M1a failure rate but was not associated with improved outcomes in patients undergoing preoperative CCRT for esophageal SCC. Pathological nodal metastasis predicted poor outcome.

INDUCTION CISPLATIN AND FLUOROURACIL-BASED CHEMOTHERAPY FOLLOWED BY CONCURRENT CHEMORADIATION FOR MUSCLE-INVASIVE BLADDER CANCER

PURPOSE To evaluate a multimodality bladder-preserving therapy in patients with muscle-invasive bladder cancer. METHODS AND MATERIALS Patients with stages T2-4aN0M0 bladder cancer suitable for cystectomy underwent radical transurethral resection and induction chemotherapy, followed by concurrent chemoradiotherapy (CCRT). Patients with a Karnofsky performance status (KPS) <80 or age > or =70 years underwent Protocol A: induction chemotherapy with three cycles of the cisplatin and 5-fluorouracil (CF) regimen, and CCRT with six doses of weekly cisplatin and 64.8 Gy radiotherapy given with the shrinking-field technique. Patients with KPS > or =80 and age <70 years underwent Protocol B: induction chemotherapy with three cycles of weekly paclitaxel plus the CF regimen, and CCRT with six doses of weekly paclitaxel and cisplatin plus 64.8 Gy radiotherapy. Interval cystoscopy was employed after induction chemotherapy and when radiotherapy reached 43.2 Gy. Patients without a complete response (CR) were referred for salvage cystectomy. RESULTS Among 30 patients (median, 66 years) enrolled, 17 and 13 patients underwent Protocol A and B, respectively. After induction chemotherapy, 23 patients achieved CR. Five (17%) of 7 patients without CR underwent salvage cystectomy. Overall, 28 patients (93%) completed the protocol treatment. Of 22 patients who completed CCRT, 1 had recurrence with carcinoma in situ and 3 had distant metastases. After a median follow-up of 47 months, overall and progression-free survival rate for all patients were 77% and 54% at 3 years, respectively. Of 19 surviving patients, 15 (79%) retained functioning bladders. CONCLUSIONS Our protocols may be alternatives to cystectomy for selected patients who wish to preserve the bladder.

Branched α-(1,4) Glucans from Lentinula edodes (L10) in Combination with Radiation Enhance Cytotoxic Effect on Human Lung Adenocarcinoma through the Toll-like Receptor 4 Mediated Induction of THP-1 Differentiation/Activation

This work investigated the role of structure in the binding of polysaccharides from 10 regionally different strains of Lentinula edodes to Toll-like receptor 4 (TLR-4) on monocytes (THP-1) and the potential effect of this interaction on tumor cell viability. Principal component analysis and multiple linear regression identified arabinose, glucose 1 → 4 linkage, and molecular weights about 2700 and 534 kDa as the significant determinant factors associated with TLR-4 binding activity. The branched α-(1,4)-glucan (L10) had the strongest ability to bind to TLR-4 and induce THP-1 cell differentiation. L10 induction of the THP-1 cell differentiation, superoxide production, and cytokine production followed the TLR-4/MyD88/IKK/NFκB pathway. Coculture of irradiated human lung adenocarcinoma A549 cells with L10-activated THP-1 cells resulted in significantly decreased percentage of viable A549 cells from 66 to 37% (p = 0.018), increased levels of superoxide, interleukin-8, and RANTES, and decreased levels of angiogenin and vascular endothelial growth factor. The results indicate that L10-activated monocytes have the potential to boost the antitumor immune response and antitumor activity of radiotherapy.

Sonic Hedgehog inhibition as a strategy to augment radiosensitivity of hepatocellular carcinoma

Sonic Hedgehog (SHH) is a regulator in tumorigenesis of hepatocellular carcinoma (HCC). This study aimed to determine whether radiation‐induced SHH signaling occurs in HCC and whether SHH inhibitor acts as a radiosensitizer.

Biomarker studies on radiotherapy to hepatocellular carcinoma.

Radiotherapy (RT) has been gradually integrated into the multimodality treatment for hepatocellular carcinoma (HCC). The various patterns of failure in HCC patients undergoing RT drive the need of effective biomarkers to guide treatment decisions. Limited numbers of biomarkers have been investigated in HCC, with even fewer of them for patients treated by RT. Serum or plasma biomarkers measured by enzyme-linked immunosorbent assay were the most common practice. Of particular interest are those biomarkers that are detectable early in the course of radiotherapy which correlated with ultimate clinical outcome. Functional magnetic resonance imaging (MRI) is increasingly used to evaluate the imaging pattern indicative of disease control following RT. Positron emission tomography shows that pre-RT standard uptake values associate with various types of recurrence after treatment. Proximity ligation assay (PLA) is evolving with the unique features of dual-probe identification, ligation and amplification to allow the small volume of serum/plasma samples for evaluating multiple biomarkers. We demonstrate the screening work of biomarkers by PLA with pre- and post-RT serum samples from HCC patients undergoing RT. Efforts are being made to search for the potential biomarkers for HCC patients treated by RT.

Differences in toxicity and outcome associated with circadian variations between patients undergoing daytime and evening radiotherapy for prostate adenocarcinoma

ABSTRACT This retrospective study tested the hypothesis that disease control and treatment-related toxicity in patients undergoing high-dose radiotherapy (HDRT) for prostate cancer varies in a circadian manner. Patients with localized prostate adenocarcinoma receiving HDRT (median 78 Gy) to the prostate and involved seminal vesicle(s) without elective pelvic irradiation were divided into a daytime treatment (before 5 PM) group (n = 267) and evening treatment (after 5 PM) group (n = 142). Biochemical failure (Phoenix definition), acute and late gastrointestinal (GI) and genitourinary toxicities (Common Terminology Criteria for Adverse Events version 4), biochemical failure-free survival (BFFS) and freedom from late toxicity were assessed. Analyses were performed by binary logistic regression and Cox proportional hazard regression. The median follow-up was 68 months, and 75% of patients were ≥70 years old. Evening HDRT was significantly associated with worse freedom from ≥grade 2 late GI complications (hazard ratio = 2.96; p < 0.001). The detrimental effect of evening HDRT was significant in patients older than 70 years old (p < 0.001) but not in younger patients (p = 0.63). In a subgroup of propensity score-matched cohort with T2b–T3 disease (n = 154), the 5-year BFFS was worse in the evening group than the daytime group (72% vs. 85%, hazard ratio = 1.95, p = 0.05). Our study indicates that evening HDRT may lead to more GI complications, especially in older patients, and worse BFFS in patients with T2b–T3 disease.

Pathological stage after neoadjuvant chemoradiation and esophagectomy superiorly predicts survival in patients with esophageal squamous cell carcinoma

BACKGROUND AND PURPOSE To assess the usefulness of pathological stage according to the 7th edition of the Union for International Cancer Control-American Joint Committee on Cancer (UICC-AJCC) as a prognostic tool in patients undergoing neoadjuvant chemoradiation followed by esophagectomy (trimodality therapy, TMT) for locally advanced esophageal squamous cell carcinoma. MATERIAL AND METHODS One hundred twenty-five eligible patients completing TMT were enrolled for analysis. The clinical (cTNM7) and pathological (ypTNM7) stage groups of their tumors were prospectively classified, and re-grouped by the 6th edition (ypTNM6). Survival was analyzed using the Kaplan-Meier method. The Cox proportional hazard model and the Akaike information criterion (AIC) were used to compare the performance of staging systems. RESULTS With a median follow-up of 24.6 months, 54 patients (43.2%) died. Forty patients (32%) achieved pathological complete remission (pCR). The median survival was 31.8 months. On multivariate analysis, ypTNM7 (but not pCR or pN) was the only independent factor affecting overall survival (p<0.001). The ypTNM7 was superior to cTNM7 or ypTNM6 in predicting both overall and recurrence-free survival after TMT based on AIC values and Cox proportional hazard model analysis. CONCLUSIONS In patients with locally advanced esophageal squamous cell carcinoma undergoing TMT, ypTNM7 is the best predictor of survival.

How to Improve Therapeutic Ratio in Radiotherapy of HCC

Background: During the past two decades, external-beam radiation technology has substantially changed from traditional two-dimensional to conformal three-dimensional to intensity-modulated planning and stereotactic body radiotherapy (SBRT). Summary: Modern techniques of radiotherapy (RT) are highly focused and capable of delivering an ablative dose to targeted hepatocellular carcinoma (HCC) tumors. SBRT is an option for selected patients with limited tumor volume and non-eligibility for other invasive treatments. Moreover, RT combined with a radiation sensitizer (RS) to increase the therapeutic ratio has shown promising results in select studies, prompting further investigation of this combination. With the undetermined role of RT in treatment guidelines and variation in patterns of treatment failure after RT in patient with HCC, useful biomarkers to guide RT decision-making and selection of patients are needed and emerging. Key Message: The objective of this review is to summarize the current RS with SBRT schemes and biomarkers for patient selection used to maximize the effect of RT on HCC.