Radiotherapy & Oncology

Editorial Board

2012-05-01

Radiation-induced cardiac damage in early left breast cancer patients: Risk factors, biological mechanisms, radiobiology, and dosimetric constraints

2012-03-05

Abstract: Today there is general awareness of the potential damage to the heart in left-sided (more than in right-sided) breast cancer radiotherapy (RT). Historical changes in tumor and heart doses are presented here along with the impact of different RT techniques and volumes. Individual and pharmacological risk factors are also examined with respect to radiation damage. The biological mechanisms of harm are only partially understood, such as the radiobiology of heart damage due to the presence of various radiosensitive structures and their topographic heterogeneity. Furthermore, individual variability may expose patients to higher or lower risks of late cardiac damage or death. Damage mechanisms and radiobiological characteristics in heart irradiation are presented in relation to dosimetric and biological parameters.

Irradiation induced modest changes in murine cardiac function despite progressive structural damage to the myocardium and microvasculature

2011-11-23

Abstract: Background: Radiotherapy of thoracic and chest wall tumors increases the long-term risk of cardiotoxicity, but the underlying mechanisms are unclear.Methods: Single doses of 2, 8, or 16Gy were delivered to the hearts of mice and damage was evaluated at 20, 40, and 60weeks, relative to age matched controls. Single photon emission computed tomography (SPECT/CT) and ultrasound were used to measure cardiac geometry and function, which was related to histo-morphology and microvascular damage.Results: Gated SPECT/CT and ultrasound demonstrated decreases in end diastolic and systolic volumes, while the ejection fraction was increased at 20 and 40weeks after 2, 8, and 16Gy. Cardiac blood volume was decreased at 20 and 60weeks after irradiation. Histological examination revealed inflammatory changes at 20 and 40weeks after 8 and 16Gy. Microvascular density in the left ventricle was decreased at 40 and 60weeks after 8 and 16Gy, with functional damage to remaining microvasculature manifest as decreased alkaline phosphatase (2, 8, and 16Gy), increased von Willebrand Factor and albumin leakage from vessels (8 and 16Gy), and amyloidosis (16Gy). 16Gy lead to sudden death between 30 and 40weeks in 38% of mice.Conclusions: Irradiation with 2 and 8Gy induced modest changes in murine cardiac function within 20weeks but this did not deteriorate further, despite progressive structural and microvascular damage. This indicates that heart function can compensate for significant structural damage, although higher doses, eventually lead to sudden death.

Effect of preoperative rescue concomitant FUN/XUN-based chemo-radiotherapy for neoadjuvant chemotherapy-refractory breast cancer

2012-03-09

Abstract: Even though tumor progression under neoadjuvant chemotherapy is uncommon, its locoregional management remains absolutely unclear. What is the best time for radical surgery or radiotherapy? “Rescue” chemo-radiotherapy could be a suitable radiosensitizing strategy to further reduce tumor progression and allow curative surgery while maintaining systemic therapy.

Long-term symptoms after radiotherapy of supraclavicular lymph nodes in breast cancer patients

2012-02-10

Abstract: Background and purpose: Irradiation of the supraclavicular lymph nodes has historically increased the risk of brachial plexopathy. We report long-term symptoms after modern radiotherapy (based on 3D dose planning) in breast cancer patients with or without irradiation of the supraclavicular lymph nodes.Material and methods: We collected information from 814 women consecutively treated with adjuvant radiotherapy for breast cancer. The women had breast surgery with axillary dissection (AD) or sentinel node biopsy (SNB). The breast area was treated to 50Gy in 2.0Gy fractions. Women with >three lymph node metastases had regional radiotherapy (RRT) to the supraclavicular lymph nodes. Three to eight years after radiotherapy, they received a questionnaire asking about paraesthesia, oedema, pain, and strength in the upper limb.Results: Paraesthesia was reported by 38/192 (20%) after AD with RRT compared to 68/505 (13%) after AD without RRT (relative risk [RR] 1.47; 95% confidence interval [CI] 1.02–2.11) and by 9/112 (8%) after SNB without RRT (RR 2.46; 95% CI 1.24–4.90). Corresponding risks adjusted for oedema (RR 1.28; 95% CI 0.93–1.76) and (RR 1.75; 95% CI 0.90–3.39). In women ⩽49years with AD and RRT, 27% reported paraesthesia. No significant pain or decreased strength was reported after RRT.Conclusion: Radiotherapy to the supraclavicular lymph nodes after axillary dissection increases the occurrence of paraesthesia, mainly among younger women. When adjusted for oedema the contribution from radiotherapy is no longer formally statistically significant indicating that there is also an indirect effect mediated by the oedema.

Fat necrosis in women with early-stage breast cancer treated with accelerated partial breast irradiation (APBI) using interstitial brachytherapy

2012-01-27

Abstract: Purpose: To report the incidence of clinical, pathological and radiological fat necrosis (FN) in women treated with accelerated partial breast irradiation (APBI) using interstitial brachytherapy (BRT) for early-stage breast cancer and to study certain variables associated with it.Methods and materials: Between May 2000 and August 2008, 171 women were treated with APBI using high dose rate (HDR) BRT. Patients were treated to a dose of 34Gy/10 fractions/1week with two fractions/day after intraoperative/postoperative placement of catheters.Results: At a median follow up of 48months (SD: 28) 20 women developed FN with median time to detection being 24months (range: 4–62months, SD: 20). Actuarial 5 and 7year FN rate was 18% and 23%, respectively. Grade 1 FN was seen in 4, grade 2 in 8 and grade 4 in 8 women. Additional investigations such as aspiration/biopsy were done in 9 patients. Volume of excision was the only significant factor affecting FN (p=0.04).Conclusions: Actuarial FN rate of 18% at 5years in our study was comparable to other reported series of FN. Median time of detection of FN was 24months. Higher volume of excision resulted in an increased incidence of fat necrosis.

How does imaging frequency and soft tissue motion affect the PTV margin size in partial breast and boost radiotherapy?

2012-04-23

Abstract: Purpose: This study investigates (i) the effect of verification protocols on treatment accuracy and PTV margins for partial breast and boost breast radiotherapy with short fractionation schema (15 fractions), (ii) the effect of deformation of the excision cavity (EC) on PTV margin size, (iii) the imaging dose required to achieve specific PTV margins.Methods and materials: Verification images using implanted EC markers were studied in 36 patients. Target motion was estimated for a 15 fraction partial breast regimen using imaging protocols based on on-line and off-line motion correction strategies (No Action Level (NAL) and the extended NAL (eNAL) protocols). Target motion was used to estimate a PTV margin for each protocol. To evaluate treatment errors due to deformation of the excision cavity, individual marker positions were obtained from 11 patients. The mean clip displacement and daily variation in clip position during radiotherapy were determined and the contribution of these errors to PTV margin calculated. Published imaging dose data were used to estimate total dose for each protocol. Finally the number of images required to obtain a specific PTV margin was evaluated and hence, the relationship between PTV margins and imaging dose was investigated.Results: The PTV margin required to account for excision cavity motion, varied between 10.2 and 2.4mm depending on the correction strategy used. Average clip movement was 0.8mm and average variation in clip position during treatment was 0.4mm. The contribution to PTV margin from deformation was estimated to be small, less than 0.2mm for both off-line and on-line correction protocols.Conclusion: A boost or partial breast PTV margin of ∼10mm, is possible with zero imaging dose and workload, however, patients receiving boost radiotherapy may benefit from a margin reduction of ∼4mm with imaging doses from 0.4cGy to 25cGy using an eNAL protocol. PTV margin contributions from deformation errors are likely to be small in comparison to other sources of error, i.e., set up or delineation.

Comparison of 3D conformal breast radiation treatment plans using the anisotropic analytical algorithm and pencil beam convolution algorithm

Sua Yoo, Qiuwen Wu, Jennifer O’Daniel, Janet Horton, Fang-Fang Yin — 2012-02-20

Abstract: Purpose: To investigate (1) dosimetric differences between plans calculated using the anisotropic analytical algorithm (AAA) and pencil beam convolution (PBC) algorithm, (2) the plan quality achieved using AAA compared to PBC based on dosimetric parameters and (3) discrepancies with an independent MU verification calculation for breast treatment planning.Materials and methods: This study included 10 lumpectomy (Group I) and 10 mastectomy (Group II) cases. Target volumes were defined as breast for Group I and chest-wall for Group II based on the isodose distribution of PBC plans in order to evaluate plans. All plans were initially calculated with PBC. For study aim (1), plans were re-calculated using AAA with the same monitor units (MUs). For study aim (2), plans were calculated using AAA with modifications of wedges, subfields and beam weightings from the original plans to achieve optimal coverage. For study aim (3), independent MU verification was performed. A 3% difference between primary MUs and verification MUs was considered an action level.Results: (1) Plans using PBC overestimate the dose to the target volume compared to plans using AAA (Group I V95%=90.4%:84.4%; Group II V95%=83.0%:74.5%; PBC:AAA). (2) The new plans using AAA achieved similar target coverage to the original PBC plans based on dose–volume histograms (DVHs). Yet, the high-dose volume (V105%) was significantly larger in AAA plans than PBC plans for Group II (V105%=19.5%:24.0%). For both groups, there was a significant increase in the ipsilateral lung volume receiving low dose with AAA plans (Group I V5Gy=23.6%:39.9%; Group II V5Gy=21.2%:33.6%). Isodose distributions of AAA plans displayed insufficient coverage in the superior area. (3) In Group I, all PBC cases passed MU verification versus 30% of AAA cases. In Group II, 80% of PBC plans versus 65% of AAA plans were within the action level.Conclusions: Plans using AAA calculation can achieve a similar level of target coverage based on DVH as PBC calculation. Nevertheless, the dose distribution shows insufficient coverage in the superior area with AAA plans compared to PBC plans. The lung volume receiving the low-dose (i.e. 5Gy) is larger and the dose to the skin is greater in AAA plans than PBC plans. Compared with PBC calculation, a larger tolerance in discrepancy between AAA and independent MU verification should be allowed to account for the inadequate heterogeneity corrections in the latter.

Reducing interobserver variation of boost-CTV delineation in breast conserving radiation therapy using a pre-operative CT and delineation guidelines

2012-01-24

Abstract: Aims: To investigate whether using a pre-operative CT scan (Preop-CT) (1) decreases interobserver variation of boost-CTV delineation in breast conserving therapy (BCT), and (2) influences the size of the delineated volumes.Patients and methods: Thirty cT1-2N0-1 breast cancer patients underwent a CT-scan in radiation treatment position, prior to and after lumpectomy. Five observers delineated a boost-CTV, both with and without access to the Preop-CT. For each patient and for each observer pair, the conformity index (CI) and the distance between the centres of mass (COMd) for both boost volumes were calculated. In addition, all delineated volumes including the standard deviation (SD) with respect to the median delineation were calculated.Results: Using a Preop-CT reduced the mean COMd of the boost-CTV from 1.1cm to 1.0cm (p<0.001). No effect was seen on the CI, but the boost-CTV volume reduced from 42cc to 36cc (p=0.005), implying a reduction of interobserver variation. We saw no significant change in the SD.Conclusion: Use of a Preop-CT in BCT results in a modest but statistically significant reduction in interobserver variation of the boost-CTV delineations and in a significant reduction in the boost-CTV volume.

Adaptive radiation therapy for breast IMRT-simultaneously integrated boost: Three-year clinical experience

2012-01-27

Abstract: Purpose: It has been shown that seroma volumes decrease during breast conserving radiotherapy in a significant percentage of patients. We report on our experience with an adaptive radiation therapy (ART) strategy involving rescanning and replanning patients to take this reduction into account during a course of intensity-modulated radiation therapy with simultaneously integrated boost (IMRT-SIB).Materials: From April 2007 till December 2009, 1274 patients eligible for SIB treatment were enrolled into this protocol. Patients for which the time between the initial planning CT (CT1) and lumpectomy was less than 30days and who had an initial seroma volume >30cm3 were rescanned at day 10 of treatment (CT2) and replanned when significant changes were observed by the radiation oncologist. Patients received 28 fractions of 1.81Gy to the breast and 2.30Gy to the boost volume.Results: Nine percent (n=113) of the 1274 patients enrolled met the criteria and were rescanned. Of this group, 77% (n=87) of treatment plans were adapted. Time between surgery and CT1 (20days versus 20days for adapted and non-adapted plans, p=0.89) and time between CT1 and CT2 (21days versus 22days for adapted and non-adapted plans, p=0.43) revealed no procedural differences which might have biased our results. In the adapted plans, seroma decreased significantly from 60 to 27cm3 (p<0.001), TBV from 70 to 45cm3 (p<0.001) and PTVboost from 277 to 220cm3 (p<0.001). The volume receiving more than 95% of the boost dose (V95%(total-dose)) could be reduced by 19% (linear fit, R2=0.73) from on average 360 to 292cm3 (p<0.001). Delay in treatment and the use of a prolonged treatment schedule with different fractionation for patients with seroma could thus be prevented.Conclusion: The adaptive radiation therapy IMRT-SIB procedure has proven to be efficient and effective, leading to a clinically significant reduction of the high dose volume. Seroma present in a subgroup of patients referred for breast radiation therapy does not hamper the introduction of highly conformal IMRT-SIB techniques.

On-line optimization of intraoperative electron beam radiotherapy of the breast

2012-02-20

Abstract: Purpose: To optimize the dose delivery to the breast lumpectomy target treated with intraoperative electron beam radiotherapy (IOERT).Materials and methods: Two tools have been developed in our MU calculation software NEMO X to improve the dose homogeneity and the in-vivo dosimetry effectiveness for IOERT treatments. Given the target (tumor bed) thickness measured by the surgeon, NEMO X can provide auto dose normalization to cover 95% of the target volume with 95% of the prescription dose (PD) and a “best guess” of the expected dosimeter dose (EDD) for a deep seated in-vivo dosimeter. The tools have been validated with the data of 91 patients treated with IOERT on a LIAC mobile accelerator. In-vivo dosimetry has been performed with microMOSFETs positioned on the shielding disk inserted between the tumor bed and the chest wall.Results: On average the auto normalization showed to provide better results if compared to conventional normalization rules in terms of mean target dose (|MTD–PD|/PD⩽5% in 95% vs. 53% of pts) and V107 percentage (〈V107〉=19% vs. 32%). In-vivo dosimetry MOSFET dose (MD) showed a better correlation with the EDD guessed by our tool than just by assuming that EDD=PD (|MD–EDD|/EDD⩽5% in 57 vs. 26% of pts).Conclusions: NEMO X provides two useful tools for the on-line optimization of the dose delivery in IOERT. This optimization can help to reduce unnecessary large over-dosage regions and allows introducing reliable action levels for in-vivo dosimetry.

Phase II trial of 3D-conformal accelerated partial breast irradiation: Lessons learned from patients and physicians’ evaluation

2012-04-23

Abstract: Introduction: The present study prospectively reported both physicians’ and patients’ assessment for toxicities, cosmetic assessment and patients’ satisfaction after 3D-conformal accelerated partial breast irradiation (APBI).Materials and Methods: From October 2007 to September 2009, 30 early breast cancer patients were enrolled in a 3D-conformal APBI Phase II trial (40Gy/10 fractions/5days). Treatment related toxicities and cosmetic results were assessed by both patients and physicians at each visit (at 1, 2, 6months, and then every 6months). Patient satisfaction was also scored.Results: After a median follow-up of 27.7months, all patients were satisfied with APBI treatment, regardless of cosmetic results or late adverse events. Good/excellent cosmetic results were noticed by 80% of patients versus 92% of cases by radiation oncologists. Breast pain was systematically underestimated by physicians (8–20% vs. 16.6–26.2%; Kappa coefficient KC=0.16–0.44). Grade 1 and 2 fibrosis and/or breast retraction occurred in 7–12% of patients and were overestimated by patients (KC=0.14–0.27).Conclusions: Present results have shown discrepancies between patient and physician assessments. In addition to the assessment of efficacy and toxicity after 3D-conformal APBI, patients’ cosmetic results consideration and satisfaction should be also evaluated.

Common variants of eNOS and XRCC1 genes may predict acute skin toxicity in breast cancer patients receiving radiotherapy after breast conserving surgery

2012-01-16

Abstract: Purpose: To evaluate the impact of functional polymorphisms in genes related to DNA repair mechanisms (XRCC1, TP53, MSH2, MSH3, XPD), oxidative stress response (GSTP1, GSTA1, eNOS, SOD2) and fibroblast proliferation (TGFβ1) on the risk of acute skin toxicity in breast cancer patients receiving radiotherapy.Material and methods: Skin toxicity was scored according to the Radiation Therapy Oncology Group criteria in 286 breast cancer patients who received radiotherapy after breast conserving surgery. Genotyping was conducted by PCR-RFLP analysis and real-time PCR allelic discrimination assay on genomic DNA extracted from peripheral blood.Results: In the multivariate analysis, nominally significant associations, before multiple testing corrections, were found between XRCC1 T-77C (T carriers vs. CC, OR: 2.240, 95% CI: 1.015–4.941, P=0.046), eNOS G894T polymorphisms (TT vs. G carriers, OR: 2.473, 95% CI: 1.220–5.012, P=0.012), breast diameter (OR: 1.138, 95% CI: 1.001–1.293, P=0.048), boost dose-fractionation (3Gy vs. no boost, OR: 4.902, 95% CI: 1.458–16.483, P=0.010) and ⩾grade 2 acute radiation skin toxicity in breast cancer patients.Conclusions: As our exploratory study suggests that XRCC1 T-77C and eNOS G874T may confer an increased risk of acute skin reactions to radiotherapy in breast cancer patients, further confirmatory studies are warranted to determine the clinical significance.

TGFβ1 SNPs and radio-induced toxicity in prostate cancer patients

2012-03-02

Abstract: Background and purpose: We have performed a case-control study in 413 prostate cancer patients to test for association between TGFβ1 and the development of late normal-tissue toxicity among prostate cancer patients treated with three-dimensional conformational radiotherapy (3D-CRT)Materials and methods: Late gastrointestinal and genitourinary toxicities were assessed for at least two years after radiotherapy in 413 patients according to CTCAEvs3 scores. Codominant genotypic tests and haplotypic analyses were undertaken to evaluate the correlation between TGFβ1 SNPs rs1800469, rs1800470 and rs1800472 and radio-induced toxicity.Results: Neither the SNPs nor the haplotypes were found to be associated with the risk of late toxicity.Conclusions: We were able to exclude up to a 2-fold increase in the risk of developing late gastrointestinal and genitourinary radio-induced toxicity due to the TGFβ1 SNPs rs1800469 and rs1800470, as well as the two most frequent TGFβ1 haplotypes.

Phase II study of hypofractionated image-guided radiotherapy for localized prostate cancer: Outcomes of 55Gy in 16 fractions at 3.4Gy per fraction

2012-01-27

Abstract: Purpose: To estimate the late morbidity of a novel, hypofractionated external beam radiotherapy schedule of 55Gy in 16 fractions (4 fractions/week, 3.4Gy per fraction) for localized prostate cancer.Methods and materials: A multi-center phase 2 study enrolled seventy-three patients between September 2004 and June 2006. After insertion of fiducial gold markers, they were treated with image-guidance (IGRT) using conformal techniques with intensity-modulation, if necessary, and then followed every 6months for toxicity rating and PSA. Patient reported outcomes were collected yearly. Median follow up was 4.6years.Results: At 4years post-radiotherapy, the cumulative incidence of combined urinary and bowel grade 3 toxicity was 7% (95% CI 3–16%) and grade 2+ was 33% (95% CI 24–46%). All except two patients recovered from their grade 3 events. Patient-reported reduction of function was most pronounced at year two for urinary function (mean −7, SD 16), and at year one for bowel function (mean −7, SD 21). The cumulative incidence of biochemical (PSA nadir+2) or biopsy-proven relapse at 4years was 9% (95% CI 4–18%).Conclusions: Hypofractionated radiotherapy is clinically feasible and more convenient than conventional schedules for patients with localized prostate cancer. Phase 3 multicenter studies are on-going (NCT00126165).

Randomised trial of external beam radiotherapy alone or combined with high-dose-rate brachytherapy boost for localised prostate cancer

2012-02-20

Abstract: Background: A randomised phase-III trial compared external beam radiotherapy (EBRT) alone with EBRT combined with high-dose-rate brachytherapy boost (HDR-BTb) in localised prostate adenocarcinoma.Methods: From December 1997 to August 2005, 218 patients were assigned to EBRT alone (n=108) or EBRT followed by a temporary high-dose-rate implant (n=110). Patients were stratified according to tumour stage, PSA, Gleason score and androgen deprivation therapy (ADT). Biochemical/clinical relapse-free survival (RFS) was the primary endpoint. Secondary endpoints were overall survival (OS), urinary and bowel toxicity.Results: RFS was significantly higher in patients treated with EBRT+HDR-BTb (log rank p=0.04). In multivariate analysis treatment arm, risk category and ADT were significant covariates for risk of relapse. Differences in OS were not significant. Incidence of severe late urinary and bowel morbidity was similar.Conclusions: EBRT+HDR-BTb resulted in a significant improvement in RFS compared to EBRT alone with a 31% reduction in the risk of recurrence (p=0.01) and similar incidence of severe late urinary and rectal morbidity.

Comparison between external beam radiotherapy (70Gy/74Gy) and permanent interstitial brachytherapy in 890 intermediate risk prostate cancer patients

2012-03-07

Abstract: Purpose: Aim of this analysis was to compare biochemical no evidence of disease (bNED) rates in intermediate-risk prostate-cancer patients treated at two centres of excellence using different approaches: permanent interstitial brachytherapy (BT) and external beam radiotherapy (EBRT).Materials and methods: A total of 890 intermediate-risk prostate-cancer patients, who were treated from 1998 to 2008, were identified in the two local databases. In Utrecht 601 patients received I-125 BT applying a dose of 144Gy. In Vienna 289 patients were treated by EBRT, applying a local dose of 70Gy in 105 patients and 74Gy in 184 patients. bNED-rates (Phoenix-definition) were assessed.Results: Median follow-up was 48months (1–150). 5-Year actuarial bNED-rates were 81% for BT-patients and 75% for EBRT-patients (67% for 70Gy and 82% for 74Gy), respectively. In univariate analysis no difference between BT and EBRT could be detected. In multivariate analysis including tumour-stage, GleasonScore, initial PSA, hormonal therapy and treatment-centre (BT vs. EBRT) only T-stage, GleasonScore and PSA were found to be significant. Additional analysis including radiation dose showed the same outcome.Conclusions: Intermediate-risk prostate cancer patients treated by permanent interstitial brachytherapy show biochemical tumour-control-rates which are comparable to EBRT of 74Gy.

Outcomes following iodine-125 brachytherapy in patients with Gleason 7, intermediate risk prostate cancer: A population-based cohort study

2012-02-13

Abstract: Background and purpose: To evaluate outcome in patients with Gleason 7 prostate cancer treated with iodine-125 brachytherapy at the British Columbia Cancer Agency.Materials and methods: Between 20th July 1998 and 7th February 2006, 1500 patients underwent I-125 prostate brachytherapy without supplemental external beam radiation therapy. Of these, 439 had Gleason 7 disease; 362 had Gleason 3+4 and 77 had 4+3 disease. Generally, patients received 6months of androgen suppression. We compared biochemical no evidence of disease (bNED) between patients with Gleason ⩽6 and Gleason 7 and between Gleason 3+4 and 4+3 using the Phoenix definition of biochemical recurrence.Results: Median follow-up was 60months. Estimated 5year bNED was 97% for patients with Gleason score ⩽6 and 94% for patients with Gleason 7 disease (p=0.037). Estimated bNED was 95% and 94% for 3+4 and 4+3, respectively (p=0.791). There was no difference in bNED between implants achieving D90⩾versus

The effect of hormonal treatment on conspicuity of prostate cancer: Implications for focal boosting radiotherapy

2012-01-24

Abstract: Background and purpose: For focal boosting of prostate tumors, three questions are important regarding the use of hormonal therapy. Does prolonged hormonal treatment affect the conspicuity of tumor tissue on diffusion weighted imaging (DWI) and dynamic contrast-enhanced (DCE-MRI) images? Is tumor delineation possible in patients using hormonal treatment? Can we identify specific imaging thresholds for tumor delineation in patients after prolonged androgen deprivation?Materials and methods: Ninety-six patients were included. Using multivariate linear regression analyses, we investigated if DWI and DCE-MRI parameter maps are different in patients receiving hormonal treatment for 0–3 or >3months. Furthermore, logistic regression was performed to obtain specific imaging thresholds for tumor tissue for the two patient groups.Results: We found a significantly higher diffusion and lower perfusion of tumor tissue in the >3months hormonal treatment group compared to the 0–3 group. This resulted in lower tumor conspicuity. Nevertheless, in 18/21 of the patients in the >3months treatment group, a suspicious lesion could be defined based on the MR images. Based on logistic regression, different imaging thresholds should be set for tumor detection in the two treatment groups.Conclusions: Prolonged androgen deprivation decreases tumor conspicuity. Different imaging thresholds need to be set to delineate tumor in patients who have had prolonged hormonal treatment.

Salvage radiotherapy after prostatectomy – What is the best time to treat?

2011-11-28

Abstract: Purpose: Salvage radiotherapy (SRT) is applied routinely in patients with biochemical relapse after radical prostatectomy (RP). However, only ∼30% of these patients achieve a durable response after 10years. As a standard, 66Gy are given, ideally with a PSA below 0.5ng/ml. We tried to determine more precisely the optimal PSA for starting SRT.Material and methods: In 301 prostate cancer patients without hormonal treatment, we analysed the impact on the biochemical response (bNED) to SRT of two pre-SRT PSA levels, namely below or above the median of 0.28ng/ml.Results: The median follow-up time for the entire group was 30months. In 151 patients, SRT commenced at a PSA ⩽0.28ng/ml, in 150 at >0.28ng/ml. Eighty-two patients (27%) developed biochemical progression during follow up. The calculated two-year bNED was 74% for the entire group, 78% versus 61% for a PSA⩽or >0.28ng/ml, respectively. In multivariate analysis, pT3b, resection status, pre-SRT PSA dichotomized at median, PSA post-SRT undetectable, and PSA doubling time were statistically significant independent predictors of progression after SRT.Conclusions: Our findings suggest that a PSA of ⩽0.28ng/ml improves bNED compared with a PSA before SRT of >0.28ng/ml.

Clinical impact of margin reduction on late toxicity and short-term biochemical control for patients treated with daily on-line image guided IMRT for prostate cancer

2011-11-28

Abstract: To evaluate the impact of PTV reduction when delivering image-guided IMRT (IG-IMRT) for patients with prostate cancer. Between 2001 and 2007, 165 men were treated with daily IG-IMRT using a 3D ultrasound-based system. Median dose prescribed to the prostate was 78Gy [74Gy–78Gy]. Patients were stratified regarding the CTV to the PTV margin: group A (n=87)=5mm or group B (n=78)=10mm. Late toxicity was scored using the CTC v3.0 scale. Biochemical progression-free survival (bPFS) was calculated using the Phoenix definition. Grade 2 genitourinary toxicity was 7.0% for group A and 6.6% for group B (p=1.00). Grade 2 gastrointestinal toxicity was 1.2% and 2.6% (p=0.38). With a median follow-up of 38.3months [5.25–87.3], bPFS at 3years was 92.5% [82.4%–96.9%] in group A and 94.3% [85.5%–97.8%] in group B (p=0.84). IG-IMRT yielded very low rates of late toxicity. Margin had impact neither on short-term bPFS nor late toxicity.

Urinary morbidity after permanent prostate brachytherapy – Impact of dose to the urethra vs. sources placed in close vicinity to the urethra

2012-02-02

Abstract: Background and purpose: The impact of the dose to the urethra and sources placed close to the urethra on urinary morbidity after permanent prostate brachytherapy (PPB) is not well known.Materials and methods: Fifty-nine patients were surveyed prospectively before treatment (A), 1month after (B) and >1year after PPB (C) using a validated questionnaire (Expanded Prostate Cancer Index Composite). Computed tomography (CT) postimplant scans were performed at days 1 (Foley catheter in situ) and 30 after PPB and sources within 5mm of the urethra at day 1 were identified.Results: As opposed to the urethral dose–volume histogram, a larger number of sources within 5mm of the urethra at day 1 predicted significantly larger urinary bother score changes at times B and C – with an impact on incontinence and frequency (e.g. moderate/big problem with leaking urine in 25% vs. 3%, p=0.02; moderate/big problem with frequent urination in 33% vs. 7%, p<0.01, at time C with vs. without ⩾3 sources in a single strand placed close to the urethra).Conclusions: Placement of sources with a minimum distance of a few mm to the urethra should be a major aim to avoid urinary morbidity irrespective of the urethral dose–volume histogram.

Increasing the risk of late rectal bleeding after high-dose radiotherapy for prostate cancer: The case of previous abdominal surgery. Results from a prospective trial

2012-04-23

Abstract: Purpose: To evaluate and discuss the role of specific types of abdominal surgery (SURG) before radical radiation therapy as a risk factor for late rectal toxicity in prostate cancer patients.Methods: Results concerning questionnaire-based scored late bleeding and faecal incontinence in 718 patients with a complete follow-up of 36months were analysed, focusing on the impact of specific pre-radiotherapy abdominal/pelvic surgery procedures. Patients were accrued in the prospective study AIROPROS 0102. Different types of surgery (rectum-sigma resection, kidney resection, cholecystectomy or appendectomy) were considered as covariates together with a number of different parameters previously found to be predictive of late toxicity and including clinical as well as dosimetric parameters. Univariate (UVA) and multivariate (MVA) logistic analyses were carried out.Results: In total 69/718 patients were previously submitted to one or more surgical procedures, mostly cholecystectomy (n=21) and appendectomy (n=27). Actuarial incidences of G2–G3 and G3 bleeding were 52 (7.2%) and 24 (3.3%) respectively; 19 (2.6%) chronic incontinence events were registered.Cholecystectomy was found to be highly correlated with late rectal bleeding at UVA: OR=4.3 and p=0.006 for G2–G3 and OR=5.4 and p=0.01 for G3. Considering MVA (including dosimetric and clinical factors), G2–G3 bleeding was significantly correlated to cholecystectomy (OR=6.5, p=0.002), V75Gy (OR=1.074, p=0.003) and secondarily with appendectomy (OR=2.7, p=0.10), presence of acute radioinduced rectal bleeding (OR=1.70, p=0.21) and androgen deprivation (OR=0.67, p=0.25).Appendectomy (OR=5.9, p=0.004) and cholecystectomy (OR=5.5, p=0.016) were very strong predictors of G3 bleeding with V75Gy playing a less significant role (OR=1.037, p=0.26). Conversely, no specific surgery was correlated with actuarial or chronic incontinence.Conclusions: This analysis highlights previous SURG as the best predictor of late rectal bleeding. Among the different types of abdominal surgery, cholecystectomy and appendectomy play the major role, especially for severe late bleeding.

Urethra sparing – potential of combined Nickel–Titanium stent and intensity modulated radiation therapy in prostate cancer

Jakob Borup Thomsen, Dennis Tideman Arp, Jesper Carl — 2011-12-26

Abstract: Background and purpose: To investigate a novel method for sparing urethra in external beam radiotherapy of prostate cancer and to evaluate the efficacy of such a treatment in terms of tumour control using a mathematical model.Materials and methods: This theoretical study includes 20 patients previously treated for prostate cancer using external beam radiotherapy. All patients had a Nickel–Titanium (Ni–Ti) stent inserted into the prostate part of urethra. The stent has been used during the treatment course as an internal marker for patient positioning prior to treatment. In this study the stent is used for delineating urethra while intensity modulated radiotherapy was used for lowering dose to urethra. Evaluation of the dose plans were performed using a tumour control probability model based on the concept of uniform equivalent dose.Results: The feasibility of the urethra dose reduction method is validated and a reduction of about 17% is shown to be possible. Calculations suggest a nearly preserved tumour control probability.Conclusions: A new concept for urethra dose reduction is presented. The method relies on the use of a Ni–Ti stent as a fiducial marker combined with intensity modulated radiotherapy. Theoretical calculations suggest preserved tumour control.

Methods of verifying the output of the treatment planning system used for high dose rate (HDR) prostate brachytherapy

Aaron Huckle, Bashar Al-Qaisieh, Peter Bownes — 2011-11-18

Abstract: Objectives: To investigate the relationships between the planning target volume (PTV) and the total reference air kerma (TRAK) required to irradiate the prostate using the Nucletron microSelection 192Ir radioactive stepping source afterloader for the treatment of prostate cancer.Methods: Using 54 patient plans, the relationship between the treatment planning system (TPS) TRAK (TRAKTPS) and the estimate and planimetry prostate volumes was investigated. Linear regression analysis was used to predict the TRAK (TRAKpred) using the prostate gland height, width and length (HWL) measurements. The TRAK was corrected using a conformal index (COIN) of the plan to improve the accuracy of the model. A further 54 patient plans were then used to evaluate the outcome of the linear regression lines.Results: A formula was proposed (HxWxLxπ/5.19) to estimate the prostate volume, which showed a mean deviation from the planimetry volume of 0.0139±3.339cm3, where 69% was within ±10% of planimetry, and 96% within ±20%. Scatter graphs of TRAKTPS for 54 plans, showed a positive linear correlation, r=0.98, using the planimetry volume, and r=0.95 for the estimated volume. The further 54 treatment plans used for evaluation showed the TRAKpred was accurately predicted to ±10% for 100% of plans using the planimetry volume and 81% using the prostate volume estimate.Conclusions: The verification method proposed was found to be accurate and independent of TPS parameters, with suitable acceptance margins of ±10%.

Evaluation of the respiratory prostate motion with four-dimensional computed tomography scan acquisitions using three implanted markers

2012-04-23

Abstract: Background and purpose: During the irradiation of the prostate cancer, it is crucial to take into account the possible displacements in defining the planning target volume. The objective of this study was to specifically analyze the respiratory-induced prostate motion using a four-dimensional CT scan (4DCT).Materials and methods: Ten patients have been treated for prostate cancer in the supine position and with three implanted gold markers; they underwent a 4DCT using a GE LightSpeed16® CT scan (slice thickness 2.5mm). This acquisition was divided into 10 phases over the respiratory cycle using the Advantage4D software. For each phase, digitally-reconstructed radiographs (DRRs) were created at 0° and 90° with the view of the markers. The coordinates of each marker center were generated from the scan isocenter. The motion amplitude was: visually analyzed on the dynamic 4DCT sequences and then more precisely calculated by comparing the marker coordinates on the 10 scans.Results: There was not any difficulty in defining the coordinates of the markers on each series. No prostate motion was observed on a simple visual analysis of the dynamic 4DCT sequences. After a more specific analysis, using the coordinates of the fiducials on the 10 phases, the prostate motion remained below 1mm in all directions, except for the cranio-caudal, where it was undetectable (thereby below the slice thickness of 2.5mm).Conclusions: To our knowledge, this is the first study that evaluates the respiratory-induced prostate motion, using a 4DCT scan. Even if important prostate displacement can occur during the prostate treatment, because of the bladder or rectum filling, in the present study no respiratory-induced prostate motion was observed.

Image-guided radiotherapy using surgical clips as fiducial markers after prostatectomy: A report of total setup error, required PTV expansion, and dosimetric implications

Suisui Song, Kamil M. Yenice, Malgorzata Kopec, Stanley L. Liauw — 2011-09-07

Abstract: Purpose: To determine the total setup error and the required planning target volume (PTV) margin for prostate bed without image guided radiotherapy (IGRT), and to demonstrate the feasibility and dosimetric benefit of IGRT post prostatectomy using surgical clips.Materials and methods: Seventeen patients were treated with intensity modulated radiotherapy (IMRT) to the prostate bed with a 1cm PTV margin. Three-dimensional shifts of the surgical clips inside the prostate bed were measured with respect to the isocenter from 364 orthogonal kV image pairs, and the total setup error was calculated to determine the required PTV margin. Alternative IMRT plans using 5mm or 1cm PTV expansion were generated and compared for rectal and bladder sparing.Results: Surgical clips were reproducibly and reliably identified. The mean (standard deviation) shifts in the left–right (LR), superior–inferior (SI), and anterior–posterior (AP), axes were: −0.1mm (1.7mm), 0.6mm (2.4mm), and −2.1mm (2.6mm), respectively. The required PTV margins were calculated to be 6, 8, and 9mm in the LR, AP, and SI axis, respectively. A PTV expansion of 5mm, compared to 1cm, significantly reduced V65Gy to the rectum by 10%.Conclusions: In the absence of IGRT, a non-uniform PTV margin of 6mm LR, 8mm AP, and 9mm SI should be considered. Use of clips as fiducial markers can decrease the total setup error, enable a smaller PTV margin, and improve rectal sparing.

Incidence of skin recurrence after breast cancer surgery

2012-01-24

In a study of interobserver variations in delineating the breast for treatment planning, Reed et al. reported that interobserver differences were smallest at the breast skin surface, owing to the use of an automatically generated external skin contour . Accordingly, the RTOG breast atlas extends the breast/chest wall CTV to the skin . However, including the skin into the breast CTV is in discrepancy with planning studies that reported cropping CTV or PTV to 5mm or 6mm under the skin surface . On one hand, including the skin can impact on the need to use a bolus or a skin flash technique , with consequently increased risk of skin toxicity. On the other hand, excluding the skin could cause an unwanted underdosage. There is a need to discuss whether the breast’s skin should be a treatment target or not.

Important ESTRO dates

2012-05-01

Radiotherapy & Oncology

Editorial Board

Contents

Radiation-induced cardiac damage in early left breast cancer patients: Risk factors, biological mechanisms, radiobiology, and dosimetric constraints

Irradiation induced modest changes in murine cardiac function despite progressive structural damage to the myocardium and microvasculature

Effect of preoperative rescue concomitant FUN/XUN-based chemo-radiotherapy for neoadjuvant chemotherapy-refractory breast cancer

Long-term symptoms after radiotherapy of supraclavicular lymph nodes in breast cancer patients

Fat necrosis in women with early-stage breast cancer treated with accelerated partial breast irradiation (APBI) using interstitial brachytherapy

How does imaging frequency and soft tissue motion affect the PTV margin size in partial breast and boost radiotherapy?

Comparison of 3D conformal breast radiation treatment plans using the anisotropic analytical algorithm and pencil beam convolution algorithm

Reducing interobserver variation of boost-CTV delineation in breast conserving radiation therapy using a pre-operative CT and delineation guidelines

Adaptive radiation therapy for breast IMRT-simultaneously integrated boost: Three-year clinical experience

On-line optimization of intraoperative electron beam radiotherapy of the breast

Phase II trial of 3D-conformal accelerated partial breast irradiation: Lessons learned from patients and physicians’ evaluation

Common variants of eNOS and XRCC1 genes may predict acute skin toxicity in breast cancer patients receiving radiotherapy after breast conserving surgery

TGFβ1 SNPs and radio-induced toxicity in prostate cancer patients

Phase II study of hypofractionated image-guided radiotherapy for localized prostate cancer: Outcomes of 55Gy in 16 fractions at 3.4Gy per fraction

Randomised trial of external beam radiotherapy alone or combined with high-dose-rate brachytherapy boost for localised prostate cancer

Comparison between external beam radiotherapy (70Gy/74Gy) and permanent interstitial brachytherapy in 890 intermediate risk prostate cancer patients

Outcomes following iodine-125 brachytherapy in patients with Gleason 7, intermediate risk prostate cancer: A population-based cohort study

The effect of hormonal treatment on conspicuity of prostate cancer: Implications for focal boosting radiotherapy

Salvage radiotherapy after prostatectomy – What is the best time to treat?

Clinical impact of margin reduction on late toxicity and short-term biochemical control for patients treated with daily on-line image guided IMRT for prostate cancer

Urinary morbidity after permanent prostate brachytherapy – Impact of dose to the urethra vs. sources placed in close vicinity to the urethra

Increasing the risk of late rectal bleeding after high-dose radiotherapy for prostate cancer: The case of previous abdominal surgery. Results from a prospective trial

Urethra sparing – potential of combined Nickel–Titanium stent and intensity modulated radiation therapy in prostate cancer

Methods of verifying the output of the treatment planning system used for high dose rate (HDR) prostate brachytherapy

Evaluation of the respiratory prostate motion with four-dimensional computed tomography scan acquisitions using three implanted markers

Image-guided radiotherapy using surgical clips as fiducial markers after prostatectomy: A report of total setup error, required PTV expansion, and dosimetric implications

Incidence of skin recurrence after breast cancer surgery

Important ESTRO dates