Daily online bony correction is required for prostate patients without fiducial markers or soft-tissue imaging

Aim

To compare online position verification strategies with offline correction protocols for patients undergoing definitive prostate radiotherapy.

Materials and methods

We analysed 50 patients with implanted fiducial markers undergoing curative prostate radiation treatment, all of whom underwent daily kilovoltage imaging using an on-board imager. For each treatment, patients were set-up initially with skin tattoos and in-room lasers. Orthogonal on-board imager images were acquired and the couch shift to match both bony anatomy and the fiducial markers recorded. The set-up error using skin tattoos and offline bone correction was compared with online bone correction. The fiducial markers were used as the reference.

Results

Data from 1923 fractions were analysed. The systematic error was ≤1 mm for all protocols. The average random error was 2-3 mm for online bony correction and 3-5 mm for skin tattoos or offline-bone. Online-bone showed a significant improvement compared with offline-bone in the number of patients with >5 mm set-up errors for >10% (P < 0.001) and >20% (P < 0.003) of their fractions.

Conclusions

Online correction to bony anatomy reduces both systematic and random set-up error in patients undergoing prostate radiotherapy, and is superior to offline correction methods for those patients not suitable for fiducial markers or daily soft-tissue imaging.     

Prospective evaluation of quality of life after permanent prostate brachytherapy with I-125: Importance of baseline symptoms and of prostate-V150

Background and purpose

Detailed knowledge of quality of life (QoL) after permanent I-125 brachytherapy may aid in counselling patients with early-stage prostate cancer.

Materials and methods

Seventy-four consecutive patients with low-risk prostate cancer were asked to complete the EORTC QLQ-C30 questionnaire with the prostate-specific PR25 module before implant, four weeks and one year after implant (response rates 97%, 88% and 89%, respectively). Implant characteristics were correlated with QoL scores.

Results

Global QoL was stable from pre-treatment to one year after implant and similar to age-adjusted scores of healthy controls. Significant changes versus baseline in QLQ-C30 domains were worsened social function at four weeks, increased constipation at four weeks and at one year and improved emotional function at one year. PR25 urinary symptoms were significantly increased at four weeks and, despite some improvement, at one year; bowel symptoms were slightly increased. Both types of symptoms were most strongly related with pre-treatment symptom scores. Prostate-V150 was the only implant parameter significantly associated with both urinary and bowel symptoms at four weeks and one year.

Conclusions

Limiting the high-dose subvolume in the prostate may be beneficial to reduce urinary and bowel symptoms but the major determinant of symptoms after I-125 implant is the baseline symptom level.     

Intra-fraction prostate displacement in radiotherapy estimated from pre- and post-treatment imaging of patients with implanted fiducial markers

Purpose

To determine intra-fraction displacement of the prostate gland from imaging pre- and post-radiotherapy delivery of prostate cancer patients with three implanted fiducial markers.

Methods and materials

Data were collected from 184 patients who had two orthogonal X-rays pre- and post-delivery on at least 20 occasions using a Varian On Board kV Imaging system. A total of 5778 image pairs covering time intervals between 3 and 30 min between pre- and post-imaging were evaluated for intra-fraction prostate displacement.

Results

The mean three dimensional vector shift between images was 1.7 mm ranging from 0 to 25 mm. No preferential direction of displacement was found; however, there was an increase of prostate displacement with time between images. There was a large variation in typical shifts between patients (range 1 ± 1 to 6 ± 2 mm) with no apparent trends throughout the treatment course. Images acquired in the first five fractions of treatment could be used to predict displacement patterns for individual patients.

Conclusion

Intra-fraction motion of the prostate gland appears to be a limiting factor when considering margins for radiotherapy. Given the variation between patients, a uniform set of margins for all patients may not be satisfactory when high target doses are to be delivered.     

A comparison of dose-volume constraints derived using peak and longitudinal definitions of late rectal toxicity

Background and purpose

Accurate reporting of complications following radiotherapy is an important part of the feedback loop to improve radiotherapy techniques. The definition of toxicity is normally regarded as the maximum or peak (P) grade of toxicity reported over the follow-up period. An alternative definition (integrated longitudinal toxicity (ILT)) is proposed which takes into account both the severity and the duration of the complication.

Methods and materials

In this work, both definitions of toxicity were used to derive dose-volume constraints for six specific endpoints of late rectal toxicity from a cohort of patients who received prostate radiotherapy in the MRC RT01 trial. The dose-volume constraints were derived using ROC analysis for 30, 40, 50, 60, 65 and 70 Gy.

Results

Statistically significant dose-volume constraints were not derived for all dose levels tested for each endpoint and toxicity definition. However, where both definitions produced constraints, there was generally good agreement. Variation in the derived dose-volume constraints was observed to be larger between endpoints than between the two definitions of toxicity. For one endpoint (stool frequency (LENT/SOM)) statistically significant dose-volume constraints were only derived using ILT.

Conclusions

The longitudinal definition of toxicity (ILT) produced results consistent with those derived using peak toxicity and in some cases provided additional information which was not seen by analysing peak toxicity alone.     

Is there a role for endorectal balloons in prostate radiotherapy? A systematic review

Background and purpose

Endorectal balloons (ERBs) are being used in prostate radiotherapy for prostate immobilization and rectal wall (Rwall) sparing. Some of their aspects, however, have been questioned, like patient’s tolerance and their value in modern high-precision radiotherapy. This paper gives an overview of published data concerning ERB application in prostate radiotherapy.

Materials and methods

Systematic literature review based on PubMed/MEDLINE database searches.

Results

Overall, ERBs are tolerated well, although patients with pre-existing anorectal disease have an increased risk of developing ERB-related toxicity. Planning studies show reduced Rwall and anal wall (Awall) doses with ERB application. Clinical data, however, are scarce, as only one study shows reduced late rectal damage. There is no consensus about the immobilizing properties of ERBs and it is recommended to use additional set-up and correction protocols, especially because there are potential pitfalls.

Conclusion

ERBs seem well-tolerated and in planning studies reduce anorectal wall doses. This may lead to reduced anorectal toxicity, although clinical studies are warranted to confirm this hypothesis and to further investigate the immobilizing properties of ERBs, preferably in combination with advanced techniques for position verification.     

Multivariate analysis of quality of life outcome for nasopharyngeal carcinoma patients after treatment

Purpose

The study analyzed the prognostic factors of quality of life (QoL) for patients with nasopharyngeal carcinoma (NPC) after treatment, with focusing on the therapeutic benefits of the technological advances in radiotherapy (RT).

Materials and methods

A cross-sectional investigation was conducted to assess the QoL of 356 NPC patients with cancer-free survival of more than 2 years. Among them, 106 patients were treated by two-dimensional RT (2DRT), 108 by 2DRT plus three-dimensional conformal RT (3DCRT) boost, 58 by 3DCRT alone, and 84 by intensity-modulated RT (IMRT). The QoL was assessed by the EORTC QLQ-C30 questionnaire and QLQ-H&N35 module. The clinical difference of QoL scores between groups was calculated using Cohen’s D coefficient.

Results

We found NPC survivors who had a higher education level or annual family income and who had received more advanced RT treatments had better QoL outcomes. Compared with 2DRT, the impact of 3DCRT was small on most scales and moderate (Cohen’s D: 0.53-0.67) on emotional functioning, pain, and mouth opening; the impact of IMRT was moderate on nine scales and large (Cohen’s D: 0.80-0.88) on swallowing, social eating, teeth, and mouth opening.

Conclusions

In addition to socioeconomic levels, advances in RT technique played a significant role in improving QoL of NPC patients.     

Normative data for the EORTC QLQ-C30 and EORTC-sexuality items in the general Dutch population

Aim

The aim of the present study was to generate Dutch reference data for the EORTC QLQ-C30 and for five sexuality items from the EORTC QL-item bank. Furthermore, to evaluate the relative impact of self-reported health problems on these outcomes and compare the Dutch normative EORTC QLQ-C30 overall QoL with available Scandinavian and German normative data.

Methods

QLQ-C30 and sexual item normative data were obtained from the Health and Health Complaints project from CentERdata. The CentERpanel is an online household panel consisting of more than 2000 Dutch households, representative of the Dutch-speaking population in the Netherlands.

Results

The questionnaire was completed by 1731 (78%) CentERpanel members. For both men and women, functional health (except emotional functioning) decreased with age, and the symptoms pain and fatigue increased with age. Men scored statistically but never clinically significantly better on most functional scales than women. Men reported higher levels of sexual interest and activity than women. All subgroups of participants with health problems reported lower physical and role functioning and overall quality of life (QoL). Those with depression (n = 79) reported functioning scores 20-30 points lower than participants without any condition. Dutch men and women reported high levels of overall QoL as compared to previously published Scandinavian and German normative data.

Conclusion

Age, gender and other health problems are important when comparing QoL and sexuality among different cancer cohorts. Normative data on QoL and sexuality are needed to interpret QoL issues among the growing group of (long-term) cancer survivors.     

Displacement of hepatic tumor at time to exposure in end-expiratory-triggered-pulse proton therapy

Purpose

This study is to evaluate reproducibility of hepatic tumors in end-expiration and end-inspiration on free-breathing, also measure shift of hepatic tumor location in pulsed proton beams exposure in end-expiration in order to estimate feasible planning target volume (PTV) margin.

Materials and methods

Pairs (1232) of anterior and lateral radiographs from 30 patients (628 end-expiration and 604 end-inspiration phases) were analyzed using fiducial markers adjacent to the tumors. By using the co-ordinates of the marker centroid of mass related to the isocenter, intrafractional variation was compared in end-expiration and end-inspiration, and a feasible PTV margin was generated using the measured motion.

Results

The average internal motion in end-expiration was 1.1 mm, which was significantly smaller than that in end-inspiration. The mean deviation from the plan was −0.1, 0.3, and 0.1 mm in the left-right (LR), cranio-cepharal (CC), and anterior-posterior (AP) directions, respectively. The estimated PTV margins were 3.2, 3.5, and 4.6 mm, in the LR, CC, and AP directions, respectively.

Conclusions

It was indicated that localization of the targets was more reproducibility in end-expiration than that in end-inspiration. Also, feasible and practical margin values were obtained. These should contribute accuracy of respiration synchronized proton radiotherapy for liver tumors.     

Health-related quality of life after permanent I-125 brachytherapy and conformal external beam radiotherapy for prostate cancer - a matched-pair comparison

Background and purpose

The aim of the study was to compare quality of life after permanent I-125 brachytherapy (BT) and external beam radiotherapy (EBRT) for prostate cancer.

Materials and methods

A group of 104 patients (52 in each group) have been surveyed prospectively before EBRT/BT (time A), at the last day of EBRT (70.2-72.0 Gy) or one month after BT (time B), and a median time of 16 months after EBRT/BT (time C) using a validated questionnaire (Expanded Prostate Cancer Index Composite). Pairs were matched according to the following criteria: age ±5years, prostate volume ±10 cc, use of antiandrogens, and erectile function.

Results

Urinary function/bother scores decreased significantly more after BT both at time B and time C. Bowel function/bother scores tended to be higher after BT, with a lower percentage of patients with painful bowel movements (BT: 12%/27%/15%; EBRT: 19%/52%/35% at time A/B/C; p < 0.05 for differences at times B/C) and rectal bleeding (BT: 12%/12%/12%; EBRT: 8%/14%/17%). No difference concerning erectile dysfunction was found (67% vs. 61% with preserved erections firm enough for intercourse after BT vs. EBRT at time C).

Conclusions

BT was associated with higher urinary, but lower rectal toxicity. The risk of treatment-associated erectile dysfunction did not differ between these methods.     

High-dose radiotherapy or concurrent chemo-radiation in lung cancer patients only induces a temporary, reversible decline in QoL

Background and purpose

Aggressive radiotherapy or concurrent chemo-radiation therapy for lung cancer leads to a high incidence of severe, mostly esophageal, toxicity. The purpose of this study was to investigate the evolution of quality of life (QoL) in patients with lung cancer, selected for curative radiotherapy (RT) or chemo-RT.

Methods

Seventy-five lung cancer patients completed a longitudinal the EORTC QLQ-C30 and LC13. Linear mixed regression models were fitted to investigate the impact of different factors on overall QoL.

Results

Overall QoL decreased shortly after the end of RT (4 points, p = 0.19), but increased back to baseline within 3 months. Mean scores of role functioning (p = 0.018), cognitive functioning (p = 0.002), dyspnoea (EORTC QLQ-LC13; p = 0.043), dysphagia (p = 0.005) and hoarseness (p = 0.029), showed a significant worsening over time. Emotional functioning (p = 0.033) improved significantly over time.Severe esophagitis (?grade 2) was reported in only 12% of the patients. Next to maximal esophageal toxicity ?grade 2 (p = .0.010), also tumor stage IIIA (p < 0.001), tumor stage IIIB (p = 0.003), gender (p = 0.042) and fatigue (p < 0.001) appeared to be significant predictors of QoL.

Conclusion

High-dose radiotherapy or concurrent chemo-radiation in the treatment of lung cancer seems to be a well-tolerated treatment option with preservation of QoL.     

Change of aesthetic and functional outcome over time and their relationship to quality of life after breast conserving therapy

Purpose

We analyzed changes in aesthetic and functional outcome over time after breast conserving therapy. Our special interest resides in the question of whether these aspects gain or loose their influence on quality of life (QoL) with temporal progress.

Patients and methods

This prospective single centre cohort study included 138 patients, treated with breast conserving surgery and consecutive radiotherapy. Patients completed two questionnaires one week and one year after surgery: the BCTOS (Breast Cancer Treatment Outcome Scale) to measure Functional, Aesthetic, and Breast Sensitivity Status and the EORTC (European Organisation for Research and Treatment of Cancer) C30-BR23 to assess QoL. We applied correlation and multiple regression analysis as statistical methods.

Results

Aesthetic and Functional Status did not change significantly over one year, whereas Breast Sensitivity Status and several QoL subscales showed significant improvement (p < 0.0001). Correlations between BCTOS scales and EORTC subscales remain similar over time. Functional and Aesthetic Status kept a strong impact on global health (Spearman’s Rho = −0.28 to −0.45 depending on time of assessment). Increasing age and poorer Functional Status shortly after surgery are predictors of a decline in global health over one year (p < 0.001).

Conclusion

Functional and aesthetic outcome after breast conserving surgery maintain their impact on QoL over a one year follow-up period and are valuable predictors of QoL.     

Association between single nucleotide polymorphisms in the gene for XRCC1 and radiation-induced late toxicity in prostate cancer patients

Background and purpose

Polymorphisms in genes responsible for DNA damage signaling and repair might modulate DNA repair capacity and, therefore, affect cell and tissue response to radiation and influence individual radiosensitivity. The purpose of the present prospective investigation was to evaluate the association of single nucleotide polymorphisms in XRCC1 with radiation-induced late side effects in prostate cancer patients treated with radiotherapy.

Material and methods

To analyze the role of XRCC1 polymorphisms for late toxicity 603 participants from the Austrian PROCAGENE study treated with three-dimensional conformal radiotherapy were included in the present investigation. Three non-synonymous candidate polymorphisms in the X-ray repair cross-complementing group 1 (XRCC1) gene (Arg194Trp; Arg280His; Arg399Gln) were selected and determined by 5´-nuclease (TaqMan) assays.

Results

Within a median follow-up time of 35 months, 91 patients (15.7%) developed high-grade late toxicities (defined as late bladder and/or rectal toxicity RTOG ? 2). In a Kaplan-Meier analysis, carriers of the XRCC1 Arg280His polymorphism were at decreased risk of high-grade late toxicity (p = 0.022), in multivariate analysis including clinical and dosimetric parameters as potential confounders the XRCC1 Arg280His polymorphism remained a significant predictor for high-grade late toxicity (HR = 0.221, 95% CI 0.051-0.956; p = 0.043). No significant associations were found for the remaining polymorphisms.

Conclusions

We conclude that the XRCC1 Arg280His polymorphism may be protective against the development of high-grade late toxicity after radiotherapy in prostate cancer patients.     

Dose-volume thresholds and smoking status for the risk of treatment-related pneumonitis in inoperable non-small cell lung cancer treated with definitive radiotherapy

Purpose

To identify clinical risk factors and dose-volume thresholds for treatment-related pneumonitis (TRP) in patients with non-small cell lung cancer (NSCLC).

Methods and materials

Data were retrospectively collected from patients with inoperable NSCLC treated with radiotherapy with or without chemotherapy. TRP was graded according to Common Terminology Criteria for Adverse Events, version 3.0, with time to grade ?3 TRP calculated from start of radiotherapy. Clinical factors and dose-volume parameters were analyzed for their association with risk of TRP.

Results

Data from 576 patients (75% with stage III NSCLC) were included in this study. The Kaplan-Meier estimate of the incidence of grade ?3 TRP at 12 months was 22%. An analysis of dose-volume parameters identified a threshold dose-volume histogram (DVH) curve defined by V₂₀ ?25%, V₂₅ ?20%, V₃₅ ?15%, and V₅₀ ?10%. Patients with lung DVHs satisfying these constraints had only 2% incidence of grade ?3 TRP. Smoking status was the only clinical factor that affected the risk of TRP independent of dosimetric factors.

Conclusions

The risk of TRP varied significantly, depending on radiation dose-volume parameters and patient smoking status. Further studies are needed to identify biological basis of smoking effect and methods to reduce the incidence of TRP.     

Is a single arc sufficient in volumetric-modulated arc therapy (VMAT) for complex-shaped target volumes?

Purpose

To compare step-and-shoot intensity-modulated radiotherapy (ss-IMRT) with volumetric-modulated arc therapy (VMAT) for complex-shaped target volumes with a simultaneous integrated boost (SIB).

Materials and methods

This retrospective planning study was based on 20 patients composed of prostate cancer (n = 5), postoperative (n = 5) or primary (n = 5) radiotherapy for pharyngeal cancer and for cancer of the paranasal sinuses (n = 5); a SIB with two or three dose levels was planned in all patients. For each patient, one ss-IMRT plan with direct-machine-parameter optimization (DMPO) and VMAT plans with one to three arcs (SmartArc technique) were generated in the Pinnacle planning system.

Results

Single arc VMAT improved target coverage and dose homogeneity in radiotherapy for prostate cancer. Two and three VMAT arcs were required to achieve equivalent results compared to ss-IMRT in postoperative and primary radiotherapy for pharyngeal cancer, respectively. In radiotherapy for cancer of the paranasal sinuses, multiarc VMAT resulted in increased spread of low doses to the lenses and decreased target coverage in the region between the orbits.

Conclusions

The complexity of the target volume determined whether single arc VMAT was equivalent to ss-IMRT. Multiple arc VMAT improved results compared to single arc VMAT at cost of increased delivery times, increased monitor unites and increased spread of low doses.     

Focal salvage iodine-125 brachytherapy for prostate cancer recurrences after primary radiotherapy: A retrospective study regarding toxicity,biochemical outcome and quality of life

Purpose

Whole-gland salvage for recurrent prostate cancer (PCa) shows high failure and toxicity rates. Early and adequate localization of recurrences enables focal salvage, thereby potentially improving functional outcomes, while maintaining cancer control.

Materials and methods

Retrospective analysis yielded 20 focal salvage I125 brachytherapy patients for locally recurrent PCa after primary radiotherapy. Tumor was defined by multiparametric MRI and correspondence with transrectal biopsies. Dose data were obtained intra-operatively. The tumor was prescribed ?144 Gy. Toxicity was scored by the Common Terminology Criteria for Adverse Events version 4 (CTCAE-4). Biochemical failure (BF) was defined using the Phoenix criteria (PSA-nadir + 2.0 ng/ml). Quality of life (QoL) was measured by SF-36 Health Survey and European Organization of Research and Treatment of Cancer (EORTC) C30+3 and PR25 questionnaires.

Results

With a median follow-up of 36 months (range 10–45), six patients experienced BF, of which three had no initial response. Grade 3 genitourinary (GU) toxicity occurred in one patient (a urethral stricture). The five previously potent patients retained erectile function. QoL remained decreased with regard to urinary symptoms.

Conclusion

Focal salvage I125 brachytherapy showed one grade 3 GU toxicity in the 20 treated patients. Biochemical response and QoL were acceptable.     

Acute toxicity profile of radiotherapy in 690 children and adolescents: RiSK data

Background and purpose

The “Registry for the evaluation of side effects after radiation in childhood and adolescence” (risk) was introduced to characterize adverse effects of radiotherapy in childhood and adolescence prospectively. The aim of this analysis was to characterize the pattern of acute side effects.

Materials and methods

Since 2001, patients receiving radiotherapy in one of the German pediatric therapy trials have been registered in RiSK with detailed information regarding radiation doses to organs at risk and characterization of acute toxicities.

Results

From 2001 to May 2009, 690 patients have been characterized for acute toxicity in primary therapy. Acute toxicity ? grade 1 was observed in 506 patients. In patients irradiated in their lung and liver, patients with grade 1 or 2 acute toxicities showed higher organ volumes exposed to radiation doses <20 Gray (Gy) compared to patients without toxicities. For the salivary glands, there was a positive correlation between the acute toxicity grade and the maximum radiation dose to the organ; the lower GI tract showed a similar trend. The impact of different chemotherapy regimens on these acute side effects remains unclear. Age did not have any impact on side effects.

Conclusion

This analysis gives a comprehensive overview of the acute toxicities of radiotherapy in children and adolescents. With prolongation of follow-up, detailed analyses regarding late toxicities will be possible with the characterization of dose-volume-effect relationships.     

Treating intermediate-risk prostate cancer with hypofractionated external beam radiotherapy alone

Purpose

Intermediate-risk prostate cancer has been treated in many ways; the most effective treatment is uncertain. Hypofractionated external beam radiotherapy (HyRT) is a short and convenient alternative treatment. We report our results of HyRT in intermediate-risk patients.

Material and methods

Eighty two patients with intermediate-risk prostate cancer were treated with 3-dimensional conformal HyRT plans to the dose of 66 Gy/22 fractions prescribed at the isocenter without hormones. Intermediate-risk was defined as clinical stage T2b-T2c, or pre-treatment PSA between 10 and 20 ng/mL, or Gleason Score equal 7. The planning target volume consisted of the prostate plus a uniform 7 mm margin. Toxicity was prospectively graded by the Common Terminology Criteria version3. Biochemical relapse was defined as post-radiotherapy nadir PSA + 2 ng/mL.

Results

With a median follow-up of 51 months, 5-year actuarial biochemical recurrence free survival is 95.4%. At the last follow-up visit, grade ?2 late gastro-intestinal and genito-urinary toxicity rates were 2% and 7%, respectively. No patient ever developed grade 4 or 5 toxicity.

Conclusion

HyRT to a dose of 66 Gy in 22 fractions as a single treatment modality is convenient for patients and for the health care system and appears to provide similar results to other treatment choices.     

Quality of life among prostate cancer patients: A prospective longitudinal population-based study

Purpose

To investigate the course of quality of life (QoL) among prostate cancer patients treated with external beam radiotherapy and to compare the results with QoL of a normal age-matched reference population.

Patients and methods

The study population was composed of 227 prostate cancer patients, treated with radiotherapy. The EORTC QLQ-C30 was used to assess QoL before radiotherapy and six months, one year, two years and three years after completion of radiotherapy. Mixed model analyses were used to investigate longitudinal changes in QoL. QoL of prostate cancer patients was compared to that of a normative cohort using a multivariate analysis of covariance.

Results

A significant decline in QoL was observed after radiotherapy (p < 0.001). The addition of hormonal therapy to radiotherapy was associated with a lower level of role functioning. Patients with coronary heart disease and or chronic obstructive pulmonary disease or asthma had a significantly worse course in QoL. Although statistically significant, all differences were classified as small or trivial.

Conclusion

Prostate cancer patients experience a small worsening of QoL as compared with baseline and as compared with a normal reference population. As co-morbidity modulates patients’ post-treatment QoL, a proper assessment of co-morbidity should be included in future longitudinal analyses on QoL.     

DCEMRI of spontaneous canine tumors during fractionated radiotherapy: A pharmacokinetic analysis

Purpose

To estimate pharmacokinetic parameters from dynamic contrast-enhanced magnetic resonance (DCEMR) images of spontaneous canine tumors taken during the course of fractionated radiotherapy, and to quantify treatment-induced changes in these parameters.

Materials and methods

Six dogs with tumors in the oral or nasal cavity received fractionated conformal radiotherapy with 54 Gy given in 18 fractions. T₁-weighted DCEMR imaging was performed prior to each treatment fraction. Time-intensity curves in the tumor were extracted voxel-by-voxel, and were fitted to the Brix pharmacokinetic model. The dependence of the pharmacokinetic parameters on the accumulated radiation dose was calculated.

Results

The Brix model reproduced the time-intensity curves well. A reduction in the k_ep parameter with accumulated radiation dose was found for five (three significant) out of six cases, while the results for the A parameter were less consistent. Both pre-treatment k_ep and the change in k_ep with accumulated dose correlated significantly with tumor regression.

Conclusions

Pharmacokinetic parameters derived from DCEMR images taken during fractionated radiotherapy may predict response to radiotherapy. This may potentially impact on patient stratification and monitoring of treatment response for image-guided treatment strategies.     

Concurrent and adjuvant docetaxel with three-dimensional conformal radiation therapy plus androgen deprivation for high-risk prostate cancer: Preliminary results of a multicentre phase II trial

Background and purpose

We evaluate the feasibility of concomitant and adjuvant docetaxel combined with three-dimensional conformal radiotherapy (3D-CRT) and androgen deprivation in high-risk prostate carcinomas.

Methods

Fifty men with high-risk localized prostate cancer (16), locally advanced (28) or very high-risk prostate cancer (6) were included. Seventy Gy were delivered on prostate and seminal vesicles in 35 fractions, concurrently with weekly docetaxel (20 mg/m²). Three weeks after the completion of 3D-CRT, docetaxel was given for 3 cycles (60 mg/m²), every 3 weeks. Patients had to receive LHRH agonist during 3 years.

Results

The intent to treat analysis shows that four patients out of 15 stopped prematurely the chemotherapy due to grade 3-4 acute toxicity. In the per protocol analysis, 46 patients completed a full-dose chemoradiation regimen representing 413 cycles: five patients experienced a grade 3 toxicity, and 15 patients experienced a grade 2 toxicity. With a median follow-up of 54 months, the 5-year clinical disease-free survival was 66.72% and the 5-year survival was 92.15%.

Conclusions

3D-CRT with androgen deprivation and concurrent weekly docetaxel, followed by three cycles of adjuvant docetaxel may be considered as feasible in high-risk prostate cancer and deserved to be evaluated in a phase III randomized trial.