Dose-escalated simultaneously integrated boost photon or proton therapy in pancreatic cancer in an in-silico study: Gastrointestinal organs remain critical.

PURPOSE: To compare the dosimetric results of an in-silico study among intensity-modulated photon (IMRT) and robustly optimized intensity-modulated proton (IMPT) treatment techniques using a dose-escalated simultaneously integrated boost (SIB) approach in locally recurrent or advanced pancreatic cancer patients. MATERIAL AND METHODS: For each of 15 locally advanced pancreatic cancer patients, a volumetric-modulated arc therapy (VMAT), a Tomotherapy (TOMO), and an IMPT treatment plan was optimized on free-breathing treatment planning computed tomography (CT) images. For the photon treatment plans, doses of 66 Gy and 51 Gy, both as SIB in 30 fractions, were prescribed to the gross tumor volume (GTV) and to the planning target volume (PTV), respectively. For the proton plans, a dose prescription of 66 Gy(RBE) to the GTV and of 51 Gy(RBE) to the clinical target volume (CTV) was planned. For each SIB-treatment plan, doses to the targets and OARs were evaluated and statistically compared. RESULTS: All treatment techniques reached the prescribed doses to the GTV and CTV or PTV. The stomach and the bowel, in particular the duodenum and the small bowel, were found to be frequently exposed to doses exceeding 50 Gy, irrespective of the treatment technique. For doses below 50 Gy, the IMPT technique was statistically significant superior to both IMRT techniques regarding decreasing dose to the OARs, e.g. volume of the bowel receiving 15 Gy (V 15Gy) was reduced for IMPT compared to VMAT (p = 0.003) and TOMO (p < 0.001). CONCLUSION: With all photon and proton techniques investigated, the radiation dose to gastrointestinal OARs remained critical when treating patients with unresectable locally recurrent or advanced pancreatic cancer using a dose-escalated SIB approach.

Image-guided dose-escalated radiation therapy for localized prostate cancer with helical tomotherapy.

PURPOSE: To evaluate treatment outcomes for patients with localized prostate cancer who were treated with dose-escalated primary image-guided radiation therapy (IGRT). METHODS: We retrospectively analyzed 88 consecutive patients treated using helical tomotherapy with daily megavoltage CTs (MVCT). Patients were prescribed daily doses of 1.8 Gy to the planning target volume (PTV) and 2 Gy to the clinical target volume (CTV). Low- and favorable intermediate-risk patients received a minimum total dose of 72 Gy to the PTV and up to 80 Gy to the CTV. Unfavorable intermediate-risk and high-risk patients received a minimum total dose of 75.6 Gy to the PTV and up to 84 Gy to the CTV. We assessed freedom from biochemical relapse (FFBF), 5­year biochemical recurrence-free survival (5-bRFS), distant metastasis-free survival (5-dMFS), and cancer-specific survival (5-CSS) as well as acute and late genitourinary (GU) and gastrointestinal (GI) toxicity. RESULTS: Among our cohort, 11.4% were low-risk, 50% intermediate-risk, and 38.6% high-risk patients according to the D'Amico criteria. Median follow-up was 66 months (range 8-83 months). FFBF was 100%, 97.7%, and 90.7%; 5­bRFS was 100%, 92.8%, and 70.4%; 5­dMFS was 100%, 92.7%, and 70.4%; and 5­CSS was 100%, 97.4%, and 89.8% for low-, intermediate-, and high-risk patients, respectively. Grades 2 and 3 toxicity occurred at the following rates: acute GU toxicity 39.8% and 1.1%, acute GI toxicity 12.5% and 0%, late GU toxicity 19.3% and 4.5%, and late GI toxicity 4.5% and 1.1% of patients, respectively. No toxicity >grade 3 was observed. CONCLUSION: Risk-adapted dose-escalated IGRT with helical tomotherapy of up to 84 Gy is a feasible and well-tolerable treatment scheme with promising oncological results.

Risk adapted dose-intensified postoperative radiation therapy in prostate cancer patients using a simultaneous integrated boost technique applied with helical Tomotherapy.

BACKGROUND: Postoperative adjuvant radiation therapy (ART) in T3 and R1 prostate cancer as well as salvage radiation therapy (SRT) in case of postoperative biochemical failure (BF) are established treatments. Dose-intensified postoperative radiation therapy (RT) schemes have shown superior biochemical control accompanied by increased toxicity rates. In our study we evaluate a novel risk adapted dose-intensified postoperative RT scheme. METHODS: A consecutive series of prostate cancer patients receiving postoperative RT after radical prostatectomy using helical Tomotherapy between 04/2012 and 04/2015 was analyzed retrospectively. RT was administered using a simultaneous integrated boost (SIB) to the area at risk (37 fractions of 1.9 Gy, total dose: 70.3 Gy) being defined based on histopathological findings (T3/R1 region) and in few cases according to additional diagnostic imaging. The whole prostate bed was treated with a dose of 66.6 Gy (37 fractions of 1.8 Gy). Primary endpoints were acute and late genitourinary (GU) and gastrointestinal (GI) toxicities. Secondary endpoints included patient reported outcome as assessed by the International Prostate Symptom Score (IPSS), the International Consultation on Incontinence questionnaire (ICIQ) and prostate cancer specific Quality of Life questionnaire QLQ-PR25, as well as rates of BF. RESULTS: A total of 69 patients were analyzed. Sixteen patients underwent ART and 53 patients SRT, respectively. The median follow-up was 20 months (range, 8-41 months). Seven (10.1%) and four (5.8%) patients experienced acute grade 2 GU and GI toxicity. Two patients (2.9%) had late grade 2 GU toxicity, whereas no late grade 2 GI nor any grade 3 acute or late GU or GI events were observed. When compared to the baseline IPSS scores (p = 1.0) and ICIQ scores (p = 0.87) were not significantly different at the end of follow-up. Patient reported Quality of life (QoL) showed also no significant difference. A total of seven patients (10.1%) experienced a biochemical recurrence with the 2-year biochemical progression-free survival (bPFS) being 91%. CONCLUSIONS: Postoperative RT for prostate cancer patients with a risk adapted dose-intensified SIB using helical tomotherapy is feasible and associated with favorable acute and late GU and GI toxicity rates, no significant change of IPSS-, ICIQ scores and patient reported QoL and results in promising bPFS rates.

Intermediate-term outcome after PSMA-PET guided high-dose radiotherapy of recurrent high-risk prostate cancer patients.

BACKGROUND: By the use of PSMA positron emission tomography (PET) detection of prostate cancer lesions with a high sensitivity and specificity combined with a favorable lesion to background contrast is feasible. Therefore, PSMA-PET is increasingly used for planning of radiotherapy treatment; however, any data on intermediate-term outcome is missing so far. METHODS: Patients with high-risk or very high risk prostate cancer, referred for salvage radiotherapy (SRT, n = 22) between 2013 and 2015, underwent PSMA-PET prior to therapy. Irradiation was planned on PET data with boost to macroscopic tumors/metastases. Treatment related toxicity was measured using Common Terminology Criteria for Adverse Events (CTCAE, v4.0). RESULT: Findings in PSMA-PET led to treatment modifications in 77% of SRT patients compared to available CT information. One patient did not receive irradiation due to disseminated disease, the other patients received increased boost doses to macroscopic disease and/or inclusion of additional target volumes. Toxicity was low as only 2 patients reported toxicities > grade 1. With a Median follow-up time of 29 in patients that were not lost to follow-up, prolonged PSA responses below baseline were observed in the majority of patients (14 of 20). In hormone-naïve SRT patients (n = 11), radiotherapy led to prolonged PSA decrease in 8/11 patients, however with 3 of these 8 patients receiving repeated PSMA based irradiation of novel lesions during follow-up. CONCLUSION: PSMA-PET guided planning of radiotherapy led to change of treatment in the majority of patients. Treatment related toxicity was well tolerated and promising results regarding intermediate-term PSA decrease were observed. TRIAL REGISTRATION: No trial registration was performed due to retrospective evaluation.

Spinal cord constraints in the era of high-precision radiotherapy : Retrospective analysis of 62 spinal/paraspinal lesions with possible infringements of spinal cord constraints within a minimal volume.

OBJECTIVE: Current constraints aim to minimize the risk of radiation myelitis by the use of restrictive maximal spinal cord doses, commonly 50 Gy. However, several studies suggested that a dose-volume effect could exist. Based on these observations, we evaluated patients receiving potentially excessive doses to the spinal cord within minimal volumes. PATIENTS AND METHODS: Patients receiving radiotherapy between June 2010 and May 2015 using the NovalisTM (Varian, Palo Alto, CA, USA; Brainlab, Heimstetten, Germany) radiosurgery system were retrospectively analyzed. A total of 56 patients with 62 treated lesions that had been prescribed radiation doses close to the spinal cord potentially higher than the common 50 Gy 2­Gy equivalent-dose (EQD2) constraint were selected for further analysis. Of these patients, 26 with 31 lesions had no history of previous irradiation, while 30 patients with 31 lesions had been previously irradiated within the treatment field. RESULTS: According to different dose evaluation approaches (spinal canal, spinal cord contour), 16 and 10 out of 31 primary irradiated lesions infringed constraints. For the 16 lesions violating spinal canal doses, the maximum doses ranged from 50.5 to 61.9 Gy EQD2. Reirradiated lesions had an average and median cumulative dose of 70.5 and 69 Gy, respectively. Dose drop-off was steep in both groups. Median overall survival was 17 months. No radiation myelitis or radiomorphological alterations were observed during follow-up. CONCLUSION: This study adds to the increasing body of evidence indicating that excessive spinal cord doses within a minimal volume, especially in a reirradiation setting with topographically distinct high-point doses, may be given to patients after careful evaluation of treatment- and tumor-associated risks.

Unilateral and bilateral neck SIB for head and neck cancer patients : Intensity-modulated proton therapy, tomotherapy, and RapidArc.

AIM: To compare simultaneous integrated boost plans for intensity-modulated proton therapy (IMPT), helical tomotherapy (HT), and RapidArc therapy (RA) for patients with head and neck cancer. PATIENTS AND METHODS: A total of 20 patients with squamous cell carcinoma of the head and neck received definitive chemoradiation with bilateral (n = 14) or unilateral (n = 6) neck irradiation and were planned using IMPT, HT, and RA with 54.4, 60.8, and 70.4 GyE/Gy in 32 fractions. Dose distributions, coverage, conformity, homogeneity to planning target volumes (PTV)s and sparing of organs at risk and normal tissue were compared. RESULTS: All unilateral and bilateral plans showed excellent PTV coverage and acceptable dose conformity. For unilateral treatment, IMPT delivered substantially lower mean doses to contralateral salivary glands (< 0.001-1.1 Gy) than both rotational techniques did (parotid gland: 6-10 Gy; submandibular gland: 15-20 Gy). Regarding the sparing of classical organs at risk for bilateral treatment, IMPT and HT were similarly excellent and RA was satisfactory. CONCLUSION: For unilateral neck irradiation, IMPT may minimize the dry mouth risk in this subgroup but showed no advantage over HT for bilateral neck treatment regarding classical organ-at-risk sparing. All methods satisfied modern standards regarding toxicity and excellent target coverage for unilateral and bilateral treatment of head and neck cancer at the planning level.

Simultaneous Integrated Boost (SIB): RapidArc and Tomotherapy Plan Comparison for Unilateral and Bilateral Neck Irradiation.

AIM: The aim of the present study was to compare simultaneous integrated boost (SIB) plans using volumetric modulated arc therapy (RapidArc®; RA) or tomotherapy (TT) for bilateral (BL) and unilateral (UL) treatment in head-and-neck cancer (HNC) patients. MATERIAL AND METHODS: Seventeen computed tomography scans (CTs) of 16 patients with SIB were replanned using TT and RA. We defined three groups: All, UL and BL, compared the dose distributions, homogeneity, conformity to planning target volume (PTV), organs at risk (OAR) and healthy tissue (HT) sparing. We evaluated a therapeutic-width index (TWI) based on PTV coverage and parotid gland (PG) sparing. RESULTS: PTV coverage for RA and TT was equivalent for all groups. UL irradiation resulted in similar doses to the HT for both techniques but TT achieved better sparing of spinal cord, larynx and contralateral PGs. TT provided better homogeneity. RA gave better conformity. CONCLUSION: Both methods achieved clinically acceptable results for UL and BL treatment, RA with better dose conformity to elective PTV, TT with better OAR sparing and homogeneity.

Which technique for radiation is most beneficial for patients with locally advanced cervical cancer? Intensity modulated proton therapy versus intensity modulated photon treatment, helical tomotherapy and volumetric arc therapy for primary radiation - an intraindividual comparison.

BACKGROUND: To compare highly sophisticated intensity-modulated radiotherapy (IMRT) delivered by either helical tomotherapy (HT), RapidArc (RA), IMRT with protons (IMPT) in patients with locally advanced cervical cancer. METHODS AND MATERIALS: Twenty cervical cancer patients were irradiated using either conventional IMRT, VMAT or HT; ten received pelvic (PEL) and ten extended field irradiation (EFRT). The dose to the planning-target volume A (PTV_A: cervix, uterus, pelvic ± para-aortic lymph nodes) was 1.8/50.4 Gy. The SIB dose for the parametrium (PTV_B), was 2.12/59.36 Gy. MRI-guided brachytherapy was administered with 5 fractions up to 25 Gy. For EBRT, the lower target constraints were 95% of the prescribed dose in 95% of the target volume. The irradiated small bowel (SB) volumes were kept as low as possible. For every patient, target parameters as well as doses to the organs at risk (SB, bladder, rectum) were evaluated intra-individually for IMRT, HT, VMAT and IMPT. RESULTS: All techniques provided excellent target volume coverage, homogeneity, conformity. With IMPT, there was a significant reduction of the mean dose (Dmean) of the SB from 30.2 ± 4.0 Gy (IMRT); 27.6 ± 5.6 Gy (HT); 34.1 ± 7.0 (RA) to 18.6 ± 5.9 Gy (IMPT) for pelvic radiation and 26.3 ± 3.2 Gy (IMRT); 24.0 ± 4.1 (HT); 25.3 ± 3.7 (RA) to 13.8 ± 2.8 Gy (IMPT) for patients with EFRT, which corresponds to a reduction of 38-52% for the Dmean (SB). Futhermore, the low dose bath (V10Gy) to the small bowel was reduced by 50% with IMPT in comparison to all photon techniques. Furthermore, Dmean to the bladder and rectum was decresed by 7-9 Gy with IMPT in patents with pelvic radiation and EFRT. CONCLUSION: All modern techniques (were proved to be dosimetrically adequate regarding coverage, conformity and homogeneity of the target. Protons offered the best sparing of small bowel and rectum and therefore could contribute to a significant reduction of acute and late toxicity in cervical cancer treatment.

Robotic radiosurgery as an alternative to brachytherapy for cervical cancer patients.

BACKGROUND AND PURPOSE: To compare MRI-guided brachytherapy (BT) and two different dose prescriptions for robotic radiosurgery (RRS) in locally advanced cervical cancer. METHODS AND MATERIALS: Eleven patients with FIGO stage IIB-IIIB cervical cancer underwent RRS instead of BT for various reasons. A total dose of 30 Gy was administered in five fractions. The maximum dose was chosen such that the prescribed dose was 70 % of the maximum dose (RRS70). To simulate BT more closely, additional plan calculations were carried out for a higher maximum dose with the same enclosing dose of 30 Gy being now 25 % of the maximum dose (RRS25). BT plans were calculated for the same patients (BTRRS). Finally, the resulting three sets of treatment plans were compared with 38 other patients treated with MRI-guided BT and the same dose prescription (BTref). Plan comparisons were performed based on DVH parameters with regard to target coverage (V100), conformation number (CN), and sparing of the organs at risk (OARs). RESULTS: The best coverage of V100 = 100 ± 0 % was obtained with RRS25, followed by RRS70 with 97.1 ± 2.7 %, BTref with 90.9 ± 8.9 %, and the intraindividual BTRRS with 80.6 ± 6.4 %. The sparing of OARs was associated with D0.1 cc, D2 cc, and D5 cc to the rectum, sigmoid, and bladder walls. OAR doses were compliant with the GEC-ESTRO guidelines and comparable among RRS70, RRS25, BTRRS, and BTref. By contrast, RRS25 could not fulfill these guidelines, exceeding considerably the tolerable dose constraints for the walls of the critical OARs. CONCLUSION: Despite of the excellent coverage and higher maximum dose, the unacceptably high exposure to the OARs disqualified RRS25 as an alternative for BT in cervical cancer patients. By contrast, RRS70 offered the best protection for the OARs, comparable to BT, and even better target coverage and conformity than BT.

Intensity modulated proton beam radiation for brachytherapy in patients with cervical carcinoma.

PURPOSE: To evaluate intensity modulated proton therapy (IMPT) in patients with cervical cancer in terms of coverage, conformity, and dose-volume histogram (DVH) parameters correlated with recommendations from magnetic resonance imaging (MRI)-guided brachytherapy. METHODS AND MATERIALS: Eleven patients with histologically proven cervical cancer underwent primary chemoradiation for the pelvic lymph nodes, the uterus, the cervix, and the parametric region, with a symmetric margin of 1 cm. The prescription was for 50.4 Gy, with 1.8 Gy per fraction. The prescribed dose to the parametria was 2.12 Gy up to 59.36 Gy in 28 fractions as a simultaneous boost. For several reasons, the patients were unable to undergo brachytherapy. As an alternative, IMPT was planned with 5 fractions of 6 Gy to the cervix, including the macroscopic tumor with an MRI-guided target definition, with an isotropic margin of 5 mm for planning target volume (PTV) definition. Groupe-Europeen de Curietherapie and European society for Radiotherapy and Oncology (GEC-ESTRO) criteria were used for DVH evaluation. Reference comparison plans were optimized for volumetric modulated rapid arc (VMAT) therapy with the RapidArc (RA). RESULTS: The dose to the high-risk volume was calculated with α/ß = 10 with 89.6 Gy. For IMPT, the clinical target volume showed a mean dose of 38.2 ± 5.0 Gy (35.0 ±1.8 Gy for RA). The D98% was 31.9 ± 2.6 Gy (RA: 30.8 ± 1.0 Gy). With regard to the organs at risk, the 2Gy Equivalent Dose (EQD2) (α/ß = 3) to 2 cm(3) of the rectal wall, sigmoid wall, and bladder wall was 62.2 ± 6.4 Gy, 57.8 ± 6.1 Gy, and 80.6 ± 8.7 Gy (for RA: 75.3 ± 6.1 Gy, 66.9 ± 6.9 Gy, and 89.0 ± 7.2 Gy, respectively). For the IMPT boost plans in combination with external beam radiation therapy, all DVH parameters correlated with <5% risk for grades 2 to 4 late gastrointestinal and genitourinary toxicity. CONCLUSION: In patients who are not eligible for brachytherapy, IMPT as a boost technique additionally to external beam radiation therapy provides good target coverage and conformity and superior DVH parameters, compared with recommendations to MRI-guided brachytherapy. For selected patients, IMPT might be a valid alternative to brachytherapy and also superior to reference VMAT plans.

Brachytherapy-emulating robotic radiosurgery in patients with cervical carcinoma.

PURPOSE: To evaluate the technique, dosimetry, dose-volume-histograms (DVHs) and acute toxicity for CyberKnife® boost irradiation instead of intra-cervical brachytherapy in patients with cervical cancer. METHODS AND MATERIALS: Eleven who were not suitable for brachytherapy with FIGO stage IIB-IIIB cervical cancer underwent primary chemoradiation. After fiducial implantation, T2 contrast-enhanced planning MRI and CT scans at 2-mm slice thickness were collected in the treatment position. The clinical target volume was defined as cervix + macroscopic residual tumour on MRI. Five fractions of 6 Gy each were prescribed to the target volume with a covering single dose 6 Gy. DVH parameters were evaluated for the target and organs at risk. Acute toxicity was documented once a week. RESULTS: DmeanPTV ranged from 33.6-40 Gy, median 36.7 Gy with a coverage of the PTV calculated to 100% of the prescribed dose ranging from 93.0-99.3% (median 97.7%). For the PTV the median CN was 0.78 (range, 0.66 to 0.87) and the median CI was 1.28 (range 1.15 to 1.52). Gastrointestinal (GI) and genitourinary (GU) toxicity was mild. There was no grade 3 or higher GI and GU toxicity. After 6 months of follow up, there were no local recurrences. For the complete treatment, a median EQD2 to 1 cc and 2 cc of the bladder wall was 98.8 Gy and 87.1 Gy, respectively. Median EQD2 to 1 cc and 2 cc of the rectal wall was 72.3 Gy and 64 Gy, respectively, correlating with a risk < 10% for Grade 2-4 late toxicity. CONCLUSIONS: CyberKnife robotic radiosurgery in patients with cervical cancer provides excellent target coverage with steep dose gradients toward normal tissues and safe DVH parameters for bladder, rectum and sigmoid. Acute toxicity was mild. Longer follow-up is needed to evaluate the oncological equality.

Optimizing image guidance frequency and implications on margins for gynecologic malignancies.

BACKGROUND: To analyze setup deviations using daily megavoltage computed tomography (MVCT) and to evaluate three MVCT frequency reducing protocols for gynecologic cancer patients treated with helical tomotherapy. METHODS: We recorded the setup errors of 56 patients with gynecological cancer observed throughout their whole course by matching their daily MVCT with the planning CT. Systematic and random errors were calculated on a patient and population basis. We defined three different protocols corresponding to MVCTs from the first five fractions (FFF), the first ten fractions (FTF) or from the first and third weeks (505). We compared theoretical. setup errors calculated using these 5 or 10 early MVCT scans with the actual errors found with the remaining fractions to to analyze the residual deviations. RESULTS: The total systematic (random) deviations had means of -2.0 (3.8)mm, 0.5 (3.4)mm, 0.5 (6.1)mm and -0.5° (0.9°) in vertical (V), longitudinal (LO), lateral (LA), and roll (R) directions, respectively. The proposed three MVCT protocols resulted in minor residual deviations. In all three protocols, 95% of all calculated residual deviations were less than or equal to 5 mm in all 3 directions. When examining the additional minimal CTV-PTV setup margins that were calculated based on these residual deviations, the 505 protocol would have allowed smaller margins than the FFF and FTF protocol, particularly in the V direction. CONCLUSIONS: For patients with gynecologic cancer, the 505-protocol led to the lowest residual deviations and therefore might offer the best approach in reducing the frequency of pre-treatment MVCTs.

Total Body Irradiation (TBI) using Helical Tomotherapy in children and young adults undergoing stem cell transplantation.

BACKGROUND: Establishing Total Body Irradiation (TBI) using Helical Tomotherapy (HT) to gain better control over dose distribution and homogeneity and to individually spare organs at risk. Because of their limited body length the technique seems especially eligible in juvenile patients. PATIENTS AND METHODS: The cohort consisted of 10 patients, 6 female and 4 male, aged 4 - 22 y with acute lymphoblastic- (ALL) or acute myeloic leukemia (AML). All patients presented with high risk disease features. Body length in treatment position ranged from 110-180 cm. Two Gy single dose was applied BID to a total dose of 12 Gy. Dose volume constraint for the PTV was 95% dose coverage for 95% of the volume. The lungs were spared to a mean dose of [less than or equal to] 10 Gy. Patients were positioned in a vac-loc bag in supine position with a 3-point head mask. RESULTS: Average D95 to the PTV was 11.7 Gy corresponding to a mean coverage of the PTV of 97.5%. Dmean for the lungs was 9.14 Gy. Grade 3-4 side effects were not observed. CONCLUSIONS: TBI using HT is feasible and well tolerated. A benefit could be demonstrated with regard to dose distribution and homogeneity and the selective dose-reduction to organs at risk.

Helical tomotherapy with simultaneous integrated boost after laparoscopic staging in patients with cervical cancer: analysis of feasibility and early toxicity.

PURPOSE: To demonstrate the feasibility and safety of the simultaneous integrated boost technique for dose escalation in combination with helical tomotherapy in patients with cervical cancer. METHODS AND MATERIALS: Forty patients (International Federation of Gynecology and Obstetrics Stage IB1 pN1-IVA) underwent primary chemoradiation with helical tomotherapy. Before therapy, 29/40 patients underwent laparoscopic pelvic and para-aortic lymphadenectomy. In 21%, 31%, and 3% of the patients, pelvic, pelvic and para-aortic, and skip metastases in the para-aortic region could be confirmed. All patients underwent radiation with 1.8-50.4 Gy to the tumor region and the pelvic (para-aortic) lymph node region (planning target volume-A), and a simultaneous boost with 2.12-59.36 Gy to the boost region (planning target volume-B). The boost region was defined using titan clips during laparoscopic staging. In all other patients, standardized borders for the planning target volume-B were defined. High-dose-rate brachytherapy was performed in 39/40 patients. The mean biologic effective dose to the macroscopic tumor ranged from 87.5 to 97.5 Gy. Chemotherapy consisted of weekly cisplatin 40 mg/m(2). Dose-volume histograms and acute gastrointestinal, genitourinary, and hematologic toxicity were evaluated. RESULTS: The mean treatment time was 45 days. The mean doses to the small bowel, rectum, and bladder were 28.5 ± 6.1 Gy, 47.9 ± 3.8 Gy, and 48 ± 3 Gy, respectively. Hematologic toxicity Grade 3 occurred in 20% of patients, diarrhea Grade 2 in 5%, and diarrhea Grade 3 in 2.5%. There was no Grade 3 genitourinary toxicity. All patients underwent curettage 3 months after chemoradiation, which confirmed complete pathologic response in 38/40 patients. CONCLUSIONS: The concept of simultaneous integrated boost for dose escalation in patients with cervical cancer is feasible, with a low rate of acute gastrointestinal and genitourinary toxicity. Whether dose escalation can be translated into improved outcome will be assessed after a longer follow-up time.

Helical tomotherapy versus conventional intensity-modulated radiation therapy for primary chemoradiation in cervical cancer patients: an intraindividual comparison.

PURPOSE: To compare intensity-modulated radiotherapy (IMRT) delivered by helical tomotherapy (HT) with conventional IMRT for primary chemoradiation in cervical cancer patients. METHODS AND MATERIALS: Twenty cervical cancer patients undergoing primary chemoradiation received radiation with HT; 10 patients underwent pelvic irradiation (PEL) and 10 extended-field irradiation (EXT). For treatment planning, the simultaneously integrated boost (SIB) concept was applied. Tumor, pelvic, with or without para-aortic lymph nodes were defined as planning target volume A (PTV-A) with a prescribed dose of 1.8/50.4 Gy (28 fractions). The SIB dose for the parametrium (PTV-B), was 2.12/59.36 Gy. The lower target constraints were 95% of the prescribed dose in 95% of the target volume, and the upper dose constraint was 107%. The irradiated small-bowel volumes were kept as low as possible. For every HT plan, a conventional IMRT plan was calculated and compared with regard to dose-volume histogram, conformity index and conformity number, and homogeneity index. RESULTS: Both techniques allowed excellent target volume coverage and sufficient SB sparing. Conformity index and conformity number results for both PTV-A and PTV-B, homogeneity index for PTV-B, and SB sparing for V45, V50, Dmax, and D1% were significantly better with HT. SB sparing was significantly better for conventional IMRT at low doses (V10). CONCLUSIONS: Both HT and conventional IMRT provide optimal treatment of cervical cancer patients. The HT technique was significantly favored with regard to target conformity, homogeneity, and SB sparing. Randomized trials are needed to assess the oncological outcome, toxicity, and clinical relevance of these differences.

Helical tomotherapy in cervical cancer patients: simultaneous integrated boost concept: technique and acute toxicity.

PURPOSE: To evaluate the acute toxicity of simultaneous integrated boost (SIB) technique for dose escalation with helical tomotherapy (HT) in patients with locally advanced cervical cancer. PATIENTS AND METHODS: 20 patients (FIGO IB1 pN1-IIIB) underwent primary chemoradiation. Prior to chemoradiation, a laparoscopic pelvic and para-aortic lymphadenectomy was performed. A boost region was defined using titanium clips during staging for planning target volume (PTV-B). Patients were treated with five weekly fractions of 1.8 Gy to a total dose of 50.4 Gy to the tumor region and the pelvic (para-aortic) lymph node region (PTV-A), and five weekly fractions of 2.12 Gy to a total dose of 59.36 Gy to the PTV-B. Chemotherapy consisted of weekly cisplatin 40 mg/m(2). 19 patients underwent brachytherapy. Dose-volume histograms were evaluated and acute gastrointestinal (GI), genitourinary (GU), and hematologic toxicity were documented (CTCAE v3.0). RESULTS: Pelvic and para-aortic lymph node metastases were confirmed in nine and four patients, respectively. Five patients refused laparoscopic staging. The mean volume of PTV-A and PTV-B was 1,570 ± 404 cm(3) and 341 ± 125 cm(3), respectively. The mean dose to the bladder, rectum, and small bowel was 47.85 Gy, 45.76 Gy, and 29.71 Gy, respectively. No grade 4/5 toxicity was observed. Grade 2/3 hematologic toxicity occurred in 50% of patients and 5% experienced grade 3 diarrhea. There was no grade 3 GU toxicity. 19 patients underwent curettage 6-9 weeks after chemoradiation without any evidence of tumor. CONCLUSION: The concept of SIB for dose escalation in patients with locally advanced cervical cancer is feasible with a low rate of acute toxicity. Whether dose escalation can translate into improved outcome will be assessed after a longer follow-up.

Intradiscal temperature monitoring using double gradient-echo pulse sequences at 1.0T.

PURPOSE: To validate an unspoiled gradient-recalled echo pulse sequence with dual echo acquisition as a means to increase temperature sensitivity while monitoring intradiscal laser ablation therapy. MATERIALS AND METHODS: Phantom experiments as well as in vitro thermal ablation simulations were performed in an open 1.0T magnetic resonance (MR) scanner. Three methods of noninvasive MR-thermometry based on the signal void decrease caused by T1-relaxation time increase (T1), the temperature-dependent proton resonance frequency (PRF) shift, and a combination of both methods with complex differences (CD) were compared. Temperature accuracy and reliability of temperature distribution were the main assessment criteria. RESULTS: The optimum temperature sensitivity was found using CD in phantom experiments. During in vitro experiments the PRF showed the smallest margin of error (T1: +/-1.64 degrees C, PRF: +/-1.23 degrees C, CD: +/-1.29 degrees C) and the best qualitative evaluation of temperature. CONCLUSION: Intradiscal temperature monitoring with an unspoiled dual-echo sequence is most accurate with PRF-thermometry in combination with the long echo time. Magnitude images with an initial short echo time permit high image detail of the heat-induced lesion.

Non-invasive magnetic resonance thermography during regional hyperthermia.

Regional hyperthermia is a non-invasive technique in which cancer tissue is exposed to moderately high temperatures of approximately 43-45 degrees C. The clinical delivery of hyperthermia requires control of the temperatures applied. This is typically done using catheters with temperature probes, which is an interventional procedure. Additionally, a catheter allows temperature monitoring only at discrete positions. These limitations can be overcome by magnetic resonance (MR) thermometry, which allows non-invasive mapping of the entire treatment area during hyperthermia application. Various temperature-sensitive MRI parameters exist and can be exploited for MR temperature mapping. The most popular parameters are proton resonance frequency shift (PRFS) (Delta phi corresponding to a frequency shift of 0.011 ppm, i.e. 0.7 Hz per degrees C at 1.5 Tesla), diffusion coefficient D (Delta D/D = 2-3 % per degrees C), longitudinal relaxation time T(1) (Delta T1/T1 approximately 1% per degrees C), and equilibrium magnetisation M(0) (Delta M(0)/M=0.3% per degrees C). Additionally, MRI temperature mapping based on temperature-sensitive contrast media is applied. The different techniques of MRI thermometry were developed to serve different purposes. The PRFS method is the most sensitive proton imaging technique. A sensitivity of +/-0.5 degrees C is possible in vivo but use of PRFS imaging remains challenging because of a high sensitivity to susceptibility effects, especially when field homogeneity is poor, e.g. on interventional MR scanners or because of distortions caused by an inserted applicator. Diffusion-based MR temperature mapping has an excellent correlation with actual temperatures in tissues. Correct MR temperature measurement without rescaling is achieved using the T(1) method, if the scaling factor is known. MR temperature imaging methods using exogenous temperature indicators are chemical shift and 3D phase sensitive imaging. TmDOTMA(-) appears to be the most promising lanthanide complex because it showed a temperature imaging accuracy of <0.3 degrees C.

Evaluation of thermometric monitoring for intradiscal laser ablation in an open 1.0 T MR scanner.

PURPOSE: The purpose of this study was to evaluate different methods of magnetic resonance thermometry (MRTh) for the monitoring of intradiscal laser ablation therapy in an open 1.0 Tesla magnetic resonance (MR) scanner. MATERIAL AND METHODS: MRTh methods based on the two endogenous MR temperature indicators of spin-lattice relaxation time T1 and water proton resonance frequency (PRF) shift were optimised and compared in vitro. For the latter, we measured the effective spin-spin relaxation times T2* in intervertebral discs of volunteers. Then we compared four gradient echo-based imaging techniques to monitor laser ablations in human disc specimens. Criteria of assessment were outline of anatomic detail, immunity against needle artefacts, signal-to-noise ratio (SNR) and accuracy of the calculated temperature. RESULTS: T2* decreased in an inverse and almost linear manner with the patients' age (r = 0.9) from 70 to 30 ms (mean of 49 ms). The optimum image quality (anatomic details, needle artefacts, SNR) and temperature accuracy (+/-1.09 degrees C for T1-based and +/-1.11 degrees C for PRF-based MRTh) was achieved with a non-spoiled gradient-echo sequence with an echo time of TE = 10 ms. CONCLUSION: Combination of anatomic and thermometric non-invasive monitoring of laser ablations in the lumbar spine is feasible. The temperature accuracy of the investigated T1- and PRF-based MRTh methods in vitro is high enough and promises to be reliable in vivo as well.

Accuracy of blood flow values determined by arterial spin labeling: a validation study in isolated porcine kidneys.

PURPOSE: To validate the accuracy of quantitative blood flow values determined using pulsed arterial spin labeling (ASL) in the preserved and reperfused porcine kidney. MATERIALS AND METHODS: Ex vivo porcine kidneys were perfused with whole blood under physiological conditions, in particular including pulsatile flow. Total flow through the kidney was determined using an ultrasound flowmeter. ASL measurements at two different inversion times and four different flow rates in the range of 70-210 mL/100 mL*minute were performed. Absolute values of blood flow and arterial transit times were determined in the kidney cortex. RESULTS: The quantitative values were in good agreement with the reference values obtained after calibration of the total flow. The greatest difference observed was 13%. CONCLUSION: Isolated organ hemoperfusion allows validating perfusion imaging techniques. The experimental setup enables long-term radiotherapeutic or toxicological studies using noninvasive ASL to monitor blood flow quantitatively.