NTCP Calculations of Five Different Irradiation Techniques for the Treatment of Thymoma.

This study provided normal tissue complication probability (NTCP) calculations from photon radiotherapy techniques in eleven patients with thymoma. Five plans were created for each participant using three-dimensional conformal radiotherapy (3D-CRT), five-field intensity modulated radiotherapy (5F-IMRT), seven-field IMRT (7F-IMRT), and volumetric modulated arc therapy with full arcs (FA-VMAT) and partial arcs (PA-VMAT). The target coverage, homogeneity index and conformation number for the planning target volume (PTV) and dosimetric parameters for the organs-at-risk (OARs) were taken from the fifty-five generated plans. The patient-specific NTCP of the lungs, heart and esophagus was calculated with an in-house software tool using differential dose-volume histograms and the equivalent uniform dose model. The PTV dose metrics from 3D-CRT were inferior to those from IMRT and VMAT plans. The dose constraints for the OARs were met in all treatment plans. The NTCP range of the lungs, heart and esophagus was 0.34-0.49%, 0.03-0.06% and 0.08-0.10%, respectively. The NTCPs of the heart for the incidence of peridarditis from IMRT and VMAT were significantly smaller than those from conformal treatment (p < 0.05). The 7F-IMRT was significantly superior to FA-VMAT in reducing the NTCP of the lungs and the risk of pneumonitis (p = 0.001). Similar superiority of 5F-IMRT over PA-VMAT for lung protection was found (p = 0.009). The presented results may be employed in the selection of the appropriate irradiation technique for restricting the complications in the adjacent OARs.

Circulating miRNAs as Potential Biomarkers in Prostate Cancer Patients Undergoing Radiotherapy.

INTRODUCTION: Disease recurrence is a major concern in patients with localized prostate cancer (PCa) following treatment with radiotherapy (RT), and few studies have evaluated the clinical relevance of microRNAs (miRNAs) prior and post-RT. PURPOSE: We aimed to investigate the significance of miRNAs in the outcomes of prostate cancer patients undergoing radiotherapy and to identify the related pathways through bioinformatics analysis. MATERIALS AND METHODS: The expression levels of miR-21, miR-106b, miR-141 and miR-375 involved in the response to radiotherapy were assessed by RT-qPCR in the serum of PCa patients (n=56) prior- and post-RT. RESULTS: Low expression levels of miR-106b prior-RT were associated with extracapsular extension and seminal vesicles invasion by the tumor (p=0.031 and 0.044, respectively). In the high-risk subgroup (n=47), post-RT expression levels of miR-21 were higher in patients with biochemical relapse (BR) compared to non-relapse (p=0.043). Also, in the salvage treatment subgroup (post-operative BR; n=20), post-RT expression levels of miR-21 and miR-106b were higher in patients with BR compared to non-relapse (p=0.043 and p=0.032, respectively). In the whole group of patients, high expression levels of miR-21 prior-RT and of miR-106b post-RT were associated with significantly shorter overall survival (OS; p=0.049 and p=0.050, respectively). No associations were observed among miR-141 and miR-375 expression levels with clinicopathological features or treatment outcome. Bioinformatics analysis revealed significant enrichment in DNA damage response pathways. CONCLUSION: Circulating miRNAs prior or post-RT may hold prognostic implications in patients with PCa.

VMAT for prostate cancer with 6-MV and 10-MV photons: Impact of beam energy on treatment plan quality and model-based secondary cancer risk estimates.

The aim of the present study was to examine the effect of the photon beam energy on the volumetric modulated arc therapy (VMAT) plan quality for prostate cancer and on the risk of secondary carcinogenesis. Separate VMAT plans with 6-MV and 10-MV photons were created for 11 low-risk patients with prostate cancer. The prescribed tumor dose was 70 Gy delivered in 28 fractions. The normal tissue integral dose and parameters associated with planning target volume and organs at risk were determined by the treatment planning data. A non-linear mechanistic model considering the effects of tumor dose fractionation and cell proliferation was employed for estimating the patient-specific lifetime attributable risk (LAR) for bladder and rectal cancer induction. Data from differential dose-volume histograms were used for these risk assessments. The mean values of the planning parameters from 6-MV treatment plans differed by 0.2-3.4% from those associated with irradiation using 10-MV photons. The LAR range for developing secondary bladder malignancies varied between 0.041 and 0.129% by the patient under investigation and the beam energy used. The corresponding range for the appearance of rectal malignant diseases was 0.047-0.153%. The mean percentage difference between the bladder cancer risks from VMAT with 6-MV and 10-MV photons was 2.6±2.3%. The corresponding difference for secondary rectal malignancies was 0.7±0.6%. Therefore, VMAT for prostate cancer with both 6-MV and 10-MV photons leads to clinically equivalent treatment plans and to similar secondary bladder and rectal cancer risks.

Secondary bladder and rectal cancer risk estimates following standard fractionated and moderately hypofractionated VMAT for prostate carcinoma.

PURPOSE: To estimate the risk for bladder and rectal cancer induction due to standard fractionated (SF) and moderately hypofractionated (HF) volumetric modulated arc therapy (VMAT) for prostate carcinoma. METHODS: Twelve patients with low or intermediate-risk of prostate cancer referred for external-beam radiotherapy were included in this study. Three computed tomography-based VMAT plans were created for each study participant. The first plan was generated by assuming patient's irradiation with SF-VMAT (78 Gy in 39 fractions). The second and third plans were created on the basis of two different HF schedules (HF-VMAT1 : 70 Gy in 30 fractions, HF:VMAT2 : 60 Gy in 20 fractions). Data from differential dose-volume histograms obtained by the above treatment plans were employed to calculate the organ equivalent dose (OED) of the bladder and rectum with the aid of a nonlinear model accounting for fractionation and proliferation effects. The calculated OED values were used to estimate the average lifetime attributable risk (LARav ) for the appearance of radiotherapy-induced secondary bladder and rectal malignancies. The lifetime risk of radiation carcinogenesis was compared with the respective organ-, and age-dependent lifetime intrinsic risk (LIR) of cancer development for unexposed males. RESULTS: The average OED of the rectum from SF-VMAT, HF-VMAT1 and HF-VMAT2 for prostate cancer was 972.0, 900.2, and 815.7 cGy, respectively. The corresponding values for bladder were 73.4, 72.3, and 71.0 cGy. The LARav for rectal cancer induction varied from 0.06% to 0.4% by the fractionation schedule used for irradiation and by the age of the patient at the time of treatment. The corresponding risk range related to the development of secondary bladder malignancies was 0.06-0.33%. The SF-VMAT, HF-VMAT1 and HF-VMAT2 led to an increase of the lifetime rectal cancer risk with respect to LIR by 2.2-9.8%, 2.0-9.1% and 1.8-8.2%, respectively, depending upon the patient's age. The corresponding elevation for bladder cancer induction was up to 8.0%, 7.9% and 7.7%. CONCLUSIONS: The use of VMAT for prostate carcinoma leads to a noteworthy increase of the lifetime risk for bladder and rectal cancer induction compared to that of unexposed people irrespective of the patient's age at the time of treatment and the applied fractionation scheme. The cancer risk data presented in this study may be taken into account by radiation oncologists and medical physicists in the selection of the optimal radiation therapy plan.

SECOND CANCER RISK FROM RADIATION THERAPY FOR COMMON SOLID TUMORS DIAGNOSED IN REPRODUCTIVE-AGED FEMALES.

This study provided second cancer risk estimates from radiation therapy for common solid tumors presented in reproductive-aged females. Three-dimensional treatment plans were generated for 10 patients with cervical, uterine, rectal, lung or breast carcinomas. The organ equivalent dose (OED) and the lifetime attributable risk (LAR) for carcinogenesis to organs receiving high doses were estimated for all study participants with a mechanistic model. This model accounts for cell-killing, tissue repair and dose fractionation effects. The patient- and organ-specific relative risk was assessed by using the LARs and the respective lifetime intrinsic cancer risks for unexposed population. The OED of the organs-at-risk varied from 17.3 to 1423.1 rad. The LAR range for bladder, colon, lung and breast cancer induction was 0.12-0.14%, 10.88-12.71%, 1.66-8.62% and 0.71-3.75%, respectively. The relative risk for the appearance of bladder, colon, lung and breast malignancies following radiotherapy was up to 1.12, 4.05, 2.42 and 1.31, respectively.

Postoperative treatment with docetaxel, cisplatin, and capecitabine (DCX) and chemoradiotherapy (CRT) with capecitabine for resected gastric adenocarcinoma.

INTRODUCTION: We conducted a feasibility study on docetaxel/capecitabine/cisplatin (DCX) with chemoradiotherapy as adjuvant treatment for gastric cancer patients. METHODS: Patients were scheduled to receive 2 cycles of DCX, followed by 50.4 Gy plus capecitabine as radiotherapy, followed by an additional 2-DCX cycles. RESULTS: From the 40 enrolled patients, 26 (65%) completed treatment as per protocol and 14 (35%) discontinued with the treatment (patients' refusal: n=6; adverse events: n=8). There were 2 toxic deaths. Grade >3 toxicity was 12.1% before and 13.3% after chemoradiotherapy. Disease progression was documented in 11 (27.5%) patients. CONCLUSIONS: No further development of this regimen is justified on the basis of poor tolerability in patients.

Peripheral organ doses from radiotherapy for heterotopic ossification of non-hip joints: is there a risk for radiation-induced malignancies?

Radiotherapy, used for heterotopic ossification (HO) management, may increase radiation risk to patients. This study aimed to determine the peripheral dose to radiosensitive organs and the associated cancer risks due to radiotherapy of HO in common non-hip joints. A Monte Carlo model of a medical linear accelerator combined with a mathematical phantom representing an average adult patient were employed to simulate radiotherapy for HO with standard AP and PA fields in the regions of shoulder, elbow and knee. Radiation dose to all out-of-field radiosensitive organs defined by the International Commission on Radiological Protection was calculated. Cancer induction risk was estimated using organ-specific risk coefficients. Organ dose change with increased field dimensions was also evaluated. Radiation therapy for HO with a 7 Gy target dose in the sites of shoulder, elbow and knee, resulted in the following equivalent organ dose ranges of 0.85-62 mSv, 0.28-1.6 mSv and 0.04-1.6 mSv, respectively. Respective ranges for cancer risk were 0-5.1, 0-0.6 and 0-1.3 cases per 10(4) persons. Increasing the field size caused an average increase of peripheral doses by 15-20%. Individual organ dose increase depends upon the primary treatment site and the distance between organ of interest and treatment volume. Relatively increased risks of more than 1 case per 10,000 patients were found for skin, breast and thyroid malignancies after treatment in the region of shoulder and for skin cancer following elbow irradiation. The estimated risk for inducing any other malignant disease ranges from negligible to low.

Intensity modulated radiation therapy versus three-dimensional conformal radiation therapy for the treatment of high grade glioma: a dosimetric comparison.

The present study compared the dosimetry of intensity-modulated radiation therapy (IMRT) and three-dimensional conformal radiation therapy (3D-CRT) techniques in patients treated for high-grade glioma. A total of 20 patients underwent computed tomography treatment planning in conjunction with magnetic resonance imaging fusion. Prescription dose and normal-tissue constraints were identical for the 3D-CRT and IMRT plans. The prescribed dose was 59.4 Gy delivered at 1.8 Gy per fraction using 4-10 MV photons. Normal-tissue dose constraints were 50-54 Gy for the optic chiasm and nerves, and 55-60 Gy for the brainstem. The IMRT plan yielded superior target coverage as compared with the 3D-CRT plan. Specifically, minimum and mean planning target volume cone down doses were 54.52 Gy and 61.74 Gy for IMRT and 50.56 Gy and 60.06 Gy for 3D-CRT (p < or = 0.01). The IMRT plan reduced the percent volume of brainstem receiving a dose greater than 45 Gy by 31% (p = 0.004) and the percent volume of brain receiving a dose greater than 18 Gy, 24 Gy, and 45 Gy by 10% (p = 0.059), 14% (p = 0.015), and 40% (p < or = 0.0001) respectively. With IMRT, the percent volume of optic chiasm receiving more than 45 Gy was also reduced by 30.40% (p = 0.047). As compared with 3D-CRT, IMRT significantly increased the tumor control probability (p < or = 0.005) and lowered the normal-tissue complication probability for brain and brainstem (p < 0.033). Intensity-modulated radiation therapy improved target coverage and reduced radiation dose to the brain, brainstem, and optic chiasm. With the availability of new cancer imaging tools and more effective systemic agents, IMRT may be used to intensify tumor doses while minimizing toxicity, therefore potentially improving outcomes in patients with high-grade glioma.

Scattered dose to gonads and associated risks from radiotherapy for common pediatric malignancies : a phantom study.

PURPOSE: To measure the scattered dose to ovaries and testes from radiotherapy for common pediatric malignancies and to assess the relevant risks for radiation-induced gonadal damage and hereditary disorders in future generations. MATERIAL AND METHODS: Radiotherapy for central nervous system tumors, acute leukemia, neuroblastoma, Hodgkin's disease, Wilms' tumor, and sarcoma was simulated on three humanoid phantoms representing patients of 5, 10, and 15 years of age. Ovarian and testicular dose measurements were performed using thermoluminescent dosimeters on a linear accelerator with multileaf collimator (MLC) producing 6-MV X-rays. The effect of lead block introduction into the primary beam on the gonadal dose was evaluated. Gonadal dose from radiotherapy for abdominal tumors was measured using an 18-MV photon beam. RESULTS: For a tumor dose range of 12-55 Gy, the scattered dose to ovaries was 0.5-62.4 cGy depending upon the patient's age (corresponding phantom) and treatment site. The corresponding dose to testes was 0.4-145.0 cGy. The use of blocks for field shaping can increase the gonadal dose up to a factor of 2.0 compared to that measured using MLC. Abdominal irradiation with 18-MV instead of 6-MV X-rays reduced the gonadal dose by more than 1.3 times. For female and male patients, the risk for induction of hereditary disorders was less than 81 x 10(-4) and 188 x 10(-4), respectively. CONCLUSION: The present dosimetric data suggest that pediatric radiotherapy is not associated with a risk for permanent damage to gonads excluded from the treatment volume. The risk for development of hereditary disorders in offspring conceived after exposure is low.

Scattered dose to thyroid from prophylactic cranial irradiation during childhood: a Monte Carlo study.

The purpose of this study was to estimate the scattered dose to thyroid from prophylactic cranial irradiation during childhood. The MCNP transport code and mathematical phantoms representing the average individual at ages 3, 5, 10, 15 and 18 years old were employed to simulate cranial radiotherapy using two lateral opposed fields. The mean radiation dose received by the thyroid gland was calculated. A 10 cm thick lead block placed on the patient's couch to shield the thyroid was simulated by MCNP code. The Monte Carlo model was validated by measuring the scattered dose to the unshielded and shielded thyroid using three different humanoid phantoms and thermoluminescense dosimetry. For a cranial dose of 18 Gy, the thyroid dose obtained by Monte Carlo calculations varied from 47 to 79 cGy depending upon the age of the child. Appropriate placement of the couch block resulted in a thyroid dose reduction by 39 to 54%. Thyroid dose values at all possible positions of the radiosensitive gland with respect to the inferior field edge at five different patient ages were found. The mean difference between Monte Carlo results and thyroid dose measurements was 9.6%.

Phase I/II trial of external irradiation plus medium-dose brachytherapy given concurrently to liposomal doxorubicin and cisplatin for advanced uterine cervix carcinoma.

BACKGROUND AND PURPOSE: Although the standard of care for patients with locally advanced uterine cervix carcinoma is cisplatin-(CDDP-)based chemotherapy and irradiation (RT), the optimal regimen remains to be elucidated. A phase I/II study was conducted to evaluate the dose limiting toxicity (DLT) and the maximum tolerated dose (MTD) of liposomal doxorubicin (Caelyx) combined with CDDP and RT for cervical cancer. PATIENTS AND METHODS: 24 patients with stage IIB-IVA were enrolled (Table 1). They all received external RT (up to 50.4 Gy) and two medium-dose rate (MDR) brachytherapy implants (20 Gy each at point A). The Caelyx starting dose of 7 mg/m2/week was increased in 5-mg/m2 increments to two levels. The standard dose of CDDP was 20-25 mg/m2/week. RESULTS: Concurrent chemoradiation (CCRT) sequelae and the DLTs (grade 3 myelotoxicity and grade 3 proctitis in five patients treated at the 17 mg/m2/week Caelyx dose level) are shown in Tables 2, 3, 4, and 5. After a median follow-up time of 17.2 months (range 4-36 months), four patients had died, 15 showed no evidence of progressive disease, and five (20.8%, 95% confidence interval [CI]: 12.5-29.1%) were alive with relapse (Figure 1). There were seven complete (29.1%, 95% CI: 19.8-38.4%) and 17 partial clinical responses (95% CI: 61.1-80.1%). The median progression-free survival was 10.4 months. Causes of death were local regional failure with or without paraaortic node relapse combined with distant metastases (Table 6). CONCLUSION: The MTD of Caelyx given concurrently with CDDP and RT was determined at the 12 mg/m2/week dose level. The above CCRT schema is a well-tolerated regimen, easy to administer in ambulatory patients, and results appear promising.