Chiao-Ling Tsai

Treatment and Dosimetric Advantages Between VMAT, IMRT, and Helical TomoTherapy in Prostate Cancer

We investigated the possible treatment and dosimetric advantage of volumetric modulated arc therapy (VMAT) over step-and-shoot intensity-modulated radiation therapy (step-and-hhoot IMRT) and helical tomotherapy (HT). Twelve prostate cancer patients undergoing VMAT to the prostate were included. Three treatment plans (VMAT, step-and-shoot IMRT, HT) were generated for each patient. The doses to clinical target volume and 95% of planning target volume were both ≥ 78 Gy. Target coverage, conformity index, dose to rectum/bladder, monitor units (MU), treatment time, equivalent uniform dose (EUD), normal tissue complication probability (NTCP) of targets, and rectum/bladder were compared between techniques. HT provided superior conformity and significantly less rectal volume exposed to 65 Gy and 40 Gy, as well as EUD/NTCP of rectum than step-and-shoot IMRT, whereas VMAT had a slight dosimetric advantage over step-and-shoot IMRT. Notably, significantly lower MUs were needed for VMAT (309.7 ± 35.4) and step-and-shoot IMRT (336.1 ± 16.8) than for HT (3368 ± 638.7) (p < 0.001). The treatment time (minutes) was significantly shorter for VMAT (2.6 ± 0.5) than step-and-shoot IMRT (3.8 ± 0.3) and HT (3.8 ± 0.6) (p < 0.001). Dose verification of VMAT using point dose and film dosimetry met the accepted criteria. VMAT and step-and-shoot IMRT have comparable dosimetry, but treatment efficiency is significantly higher for VMAT than for step-and-shoot IMRT and HT.

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.

Gemcitabine and cisplatin in a multimodality treatment for locally advanced non-small cell lung cancer.

The role of new cytotoxic agents like gemcitabine has not yet been proven in the neoadjuvant settings. We designed a phase II study to test the feasibility of using gemcitabine and cisplatin before local treatment for stage III non-small cell lung cancer patients. Patients received three cycles of induction chemotherapy of gemcitabine (1000 mg m−2, days 1, 8, 15) and cisplatin (90 mg m−2, day 15) every 4 weeks before evaluation for operability. Operable patients underwent radical resection. Inoperable patients and patients who had incomplete resection received concurrent chemoradiotherapy with daily low dose cisplatin. All patients who did not progress after local treatment received three more cycles of adjuvant chemotherapy of gemcitabine and cisplatin. Fifty-two patients received induction treatment. Two patients had complete response and 31 patients had partial response (response rate 63.5%) after induction chemotherapy. Thirty-six patients (69%) were operable. Eighteen patients (35%) had their tumours completely resected. Two patients had pathological complete response. Median overall survival was 19.1 months, projected 1-year survival was 66% and 2-year survival was 34%. Three cycles of gemcitabine and cisplatin is effective and can be used as induction treatment before surgery for locally advanced non-small cell lung cancer patients.

A randomised phase II study of weekly paclitaxel or vinorelbine in combination with cisplatin against inoperable non-small-cell lung cancer previously untreated

Phase II studies have suggested that weekly paclitaxel has a higher response rate and better toxicity profile than the conventional schedule of once every 3 or 4 weeks. Our aim was to evaluate the efficacy of weekly paclitaxel plus cisplatin (PC) vs vinorelbine plus cisplatin (VC) in chemonaïve non-small-cell lung cancer (NSCLC) patients. From October 2000 to May 2002, 140 patients were enrolled. The treatment dose was P 66 mg m−2 intravenous infusion (i.v.) on days 1, 8, and 15, and C 60 mg m−2 i.v. on day 15, or V 23 mg m−2 i.v. on days 1, 8, and 15, and C 60 mg m−2 i.v. on day 15, every 4 weeks. In all, 281 cycles of PC and 307 cycles of VC were given to the patients in the PC and VC arms, respectively. There were 26 partial responses and one complete response (overall 38.6%) in the PC arm, and no complete responses, but 27 partial responses (overall 38.6%) in the VC arm. Myelosuppression was more common in the VC arm (P<0.001). Peripheral neuropathy and myalgia were significantly more common in the PC arm (P<0.001). The median time to disease progression was 6 months in the PC arm and 8.4 months in the VC arm (P=0.0344). The median survival time was 11.7 months in the PC arm and 15.4 months in the VC arm (P=0.297). We concluded that weekly PC is not suggested for NSCLC patients due to the relatively shorter progression-free survival and more common nonhaematological toxicities.

Mathematical estimation and in vivo dose measurement for cone-beam computed tomography on prostate cancer patients

BACKGROUND AND PURPOSE Cone-beam computed tomography (CBCT) increases the doses on normal tissues. Our study sought to develop a mathematical model that would provide an estimate of and verify in vivo rectal dose from CBCT in prostate cancer patients. MATERIALS AND METHODS Thermoluminescent dosimeters (TLDs) and Rando phantoms were used to measure doses to the pelvic region. We used an endorectal balloon to measure rectal doses for 10 prostate cancer patients who underwent radiotherapy and for whom we were able to acquire CBCT images. A solid water phantom and TLDs were used to correlate the rectal doses with body thickness/widths. A mathematical method was established to simulate the dose to which the patient is exposed during CBCT for the determined body parameters. The estimated doses were compared with the measured doses to determine the effectiveness of the model. RESULTS The average measured rectal dose from CBCT was 2.8+/-0.3 cGy. The mathematical method was able to predict the rectal dose, with the limits of agreement of -0.03+/-0.18 cGy. The average difference between predictions and measurements was -1.1+/-3.6%. CONCLUSION Our mathematical model was effective in estimating the exposed dose from CBCT.

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.

Postoperative Intensity-Modulated Radiotherapy for Squamous Cell Carcinoma of the External Auditory Canal and Middle Ear: Treatment Outcomes, Marginal Misses, and Perspective on Target Delineation

PURPOSE To report outcomes of the rare disease of squamous cell carcinoma (SCC) of the external auditory canal (EAC) and middle ear treated with surgery and postoperative intensity-modulated radiotherapy (IMRT). Failure patterns related to spatial dose distribution were also analyzed to provide insight into target delineation. METHODS AND MATERIALS A retrospective review was conducted of the records of 11 consecutive patients with SCC of the EAC and middle ear who were treated with curative surgery and postoperative IMRT at one institution between January 2007 and February 2010. The prescribed IMRT dose was 60 to 66 Gy at 2 Gy per fraction. Three patients also received concurrent cisplatin-based chemotherapy, and 1 patient received concurrent oral tegafur/uracil. The median follow-up time was 19 months (range, 6-33 months). RESULTS Four patients had locoregional recurrence, yielding an estimated 2-year locoregional control rate of 70.7%. Among them, 1 patient had persistent disease after treatment, and 3 had marginal recurrence. Distant metastasis occurred in 1 patient after extensive locoregional recurrence, yielding an estimated 2-year distant control rate of 85.7%. The estimated 2-year overall survival was 67.5%. The three cases of marginal recurrence were near the preauricular space and glenoid fossa of the temporomandibular joint, adjacent to the apex of the ear canal and glenoid fossa of the temporomandibular joint, and in the postauricular subcutaneous area and ipsilateral parotid nodes, respectively. CONCLUSIONS Marginal misses should be recognized to improve target delineation. When treating SCC of the EAC and middle ear, care should be taken to cover the glenoid fossa of the temporomandibular joint and periauricular soft tissue. Elective ipsilateral parotid irradiation should be considered. The treatment planning procedure should also be refined to balance subcutaneous soft-tissue dosimetry and toxicity.

Practically acquired and modified cone-beam computed tomography images for accurate dose calculation in head and neck cancer

BackgroundOn-line cone-beam computed tomography (CBCT) may be used to reconstruct the dose for geometric changes of patients and tumors during radiotherapy course. This study is to establish a practical method to modify the CBCT for accurate dose calculation in head and neck cancer.Patients and MethodsFan-beam CT (FBCT) and Elekta’s CBCT were used to acquire images. The CT numbers for different materials on CBCT were mathematically modified to match them with FBCT. Three phantoms were scanned by FBCT and CBCT for image uniformity, spatial resolution, and CT numbers, and to compare the dose distribution from orthogonal beams. A Rando phantom was scanned and planned with intensity-modulated radiation therapy (IMRT). Finally, two nasopharyngeal cancer patients treated with IMRT had their CBCT image sets calculated for dose comparison.ResultsWith 360° acquisition of CBCT and high-resolution reconstruction, the uniformity of CT number distribution was improved and the otherwise large variations for background and high-density materials were reduced significantly. The dose difference between FBCT and CBCT was < 2% in phantoms. In the Rando phantom and the patients, the dose–volume histograms were similar. The corresponding isodose curves covering ≥ 90% of prescribed dose on FBCT and CBCT were close to each other (within 2 mm). Most dosimetric differences were from the setup errors related to the interval changes in body shape and tumor response.ConclusionThe specific CBCT acquisition, reconstruction, and CT number modification can generate accurate dose calculation for the potential use in adaptive radiotherapy.ZielDie On-line-Cone-Beam-Computertomographie (CBCT) kann zur Anpassung der Dosis bei geometrischen Änderungen der Patientenlagerung und des Tumorvolumens während der Strahlentherapie verwendet werden. Diese Studie zeigt eine praktischen Methode zur Änderung der Cone-Beam-CTs zur exakten Berechnung der Dosierung bei der Radiotherapie von Kopf- und Hals-Tumoren.Patienten und MethodenFan-Beam-CTs (FBCT) und CBCTs (Elekta) wurden zur Bildakquisition verwendet. Die CT-Dichtewerte für die verschiedenen Materialien des CBCT wurden mathematisch zur Anpassung an das FBCT verändert. Drei Phantome wurden mit FBCT und CBCT zur Bildergleichheit, räumlichen Auflösung und der Bestimmung der CT-Dichtewerte sowie zum Vergleich der Dosierungsverteilung in orthogonaler Richtung gescannt. Ein Rando-Phantom wurde gescannt und mit intensitätsmodulierter Strahlentherapie (IMRT) geplant. Schließlich wurden für zwei Nasopharynxkarzinom-Patienten, die mit IMRT behandelt wurden, die CBCT-Bilder zum Dosierungsvergleich berechnet.ErgebnisseMit der 360°-Erfassung des CBCT und einer hochaufgelösten Rekonstruktion wurden sowohl die Übereinstimmung der CT-Dichtewerte verbessert als auch die sonst großen Abweichungen des Hintergrundes und bei dichteren Materialien erheblich reduziert. Die Dosisdifferenz zwischen FBCT und CBCT lag bei den Phantomen bei < 2%. Bei den Rando-Phantomen und den Patienten waren die Dosis-Volumen-Histogramme ähnlich. Die entsprechenden Isodose-Kurven, welche ≥ 90% der Volumina der FBCT und CBCT abdeckten, lagen nahe beieinander (innerhalb von 2 mm). Die meisten Dosisunterschiede entstanden durch Positionierungsungenauigkeiten, die durch veränderte Körperkonturen und die Tumorrückbildung entstanden.SchlussfolgerungDie spezifische CBCT-Erfassung, Rekonstruktion und die Änderung der CT-Dichtewerte können eine exakte Dosisberechnung für die potentielle Verwendung in der adaptiven Strahlentherapie generieren.

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.