Urinary toxicity after high dose intensity modulated radiotherapy as primary therapy for prostate cancer

Background and purpose

Urinary toxicity plays a major role in the quality of life (QOL) of patients treated with external beam radiotherapy as primary therapy for prostate cancer.In this study we report on:(1) Incidence of acute and late GU toxicity after intensity modulated radiotherapy (IMRT) for prostate cancer at Ghent University Hospital (GUH).(2) Time evolution of pre-IMRT and IMRT-induced acute and late GU toxicity.

Materials and methods

At GUH, 260 patients with a follow-up of ?12 months were treated with IMRT for prostate cancer. The incidence and evolution of GU toxicity were recorded.

Results

Acute grades 3, 2 and 1 GU toxicity occurred in 8%, 42% and 42% of the patients, respectively. Late grades 3, 2 and 1 GU toxicity occurred in 3%, 19% and 40% of the patients, respectively.During therapy baseline grade 1 symptoms increased into grade 2 acute GU toxicity in 48%. After 1 and 2 years, 60% and 70% of the patients, respectively, had less GU symptoms when compared to the pre-treatment status.

Conclusion

IMRT induces mild GU toxicity. There is an improvement in pre-IMRT obstructive miction disorders.     

Predictors of acute bowel toxicity in patients treated with IMRT whole pelvis irradiation after prostatectomy

Purpose/objective

Whole pelvis irradiation with IMRT (WPRT-IMRT) after prostatectomy is efficient in reducing acute toxicity: however, a number of patients still experience moderate acute bowel toxicity.

Materials and methods

Ninety-six patients treated with WPRT-IMRT after prostatectomy with adjuvant or salvage intent were analysed. A number of parameters were individually recovered, including the DVHs of the intestinal cavity outside PTV and of the loops referred to both the WPRT phase and the whole treatment. Correlation between clinical-dosimetric parameters and acute bowel toxicity was investigated by logistic analyses. Best predictive cut-off values for continuous variables were assessed by ROC curves.

Results

15/96 (15.6%) Patients experienced grade 2 toxicity (no grade 3). Best dose-volume predictors were the fraction of loops receiving more than 45, 50 and 55 Gy (respectively, V45TL ? 50 cc, V50TL ? 13 cc, V55TL ? 3 cc; p-values ranging from 0.005 to 0.027). Age, GU acute toxicity, rectal acute toxicity and time between prostatectomy and IMRT were also predictors of acute bowel toxicity. Multivariate analysis showed that the most predictive independent parameters were age (OR: 1.13; 95%CI: 1.02-1.25; p = 0.021) and V50TL (?13 cc, OR: 8.2; 95%CI: 1.7-40; p = 0.009).

Conclusions

The risk of moderate acute uGI toxicity during WPRT-IMRT for post-operatively treated patients increases with age; the risk is substantially reduced in patients with small overlap between PTV and loops.     

Radical prostatectomy vs. intensity-modulated radiation therapy in the management of localized prostate adenocarcinoma

Background and purpose

To determine whether radical prostatectomy (RP) or intensity-modulated radiation therapy (IMRT) to ?72 Gy, plus hormonal therapy if indicated, results in improved biochemical disease-free survival (BDFS) in localized prostate adenocarcinoma.

Materials and methods

Between 1997 and 2005, a consecutive sample of 556 patients who underwent RP (n = 204) or IMRT (n = 352) at two referral centers was analyzed. The patients were stratified into prognostic groups based on clinical stage, Gleason score, and pretreatment prostate-specific antigen (PSA). The outcome measure was BDFS.

Results

IMRT patients had more advanced disease at baseline (p < .001). There was no difference in five-year BDFS rates between RP and IMRT in the favorable (92.8% vs. 85.3%, p = .20) or intermediate prognosis (86.7% vs. 82.2%, p = .46) subsets. A difference favoring IMRT plus hormonal therapy was seen in the poor prognosis (38.4% vs. 62.2%, p < .001) subset. Within the entire cohort, after adjustment for confounding variables, Gleason score (p < .001) and clinical stage (p < .001) predicted BDFS, but treatment modality (p = .06) did not. Within the poor prognosis subset, treatment modality (p = .006) predicted BDFS.

Conclusions

BDFS is similar between RP and IMRT for patients with a favorable or intermediate prognosis. Patients with a poor prognosis display higher BDFS when treated with IMRT to ?72 Gy plus hormonal therapy.     

Late toxicity after postprostatectomy salvage radiation therapy

Purpose

To evaluate late toxicity in patients who received salvage external beam radiotherapy (EBRT) for a detectable prostate-specific antigen (PSA) level after radical prostatectomy (RP).

Methods

A cohort of 308 consecutive patients underwent salvage EBRT from July 1987 through June 2003 for a detectable PSA level after RP. All were treated with high-energy photons (6-20 MV) to a median dose of 64.8 Gy (range: 54.0-72.4 Gy) in 1.8- to 2.0-Gy fractions.

Results

Median follow-up from the completion of EBRT was 60 months (range: 1 day-174 months). Late toxicity occurring more than 90 days after EBRT completion was identified in 41 patients (13%). Twelve patients (3.9%) had grade 2 urethral strictures and were treated with urethral dilation, 3 patients had grade 3 cystitis, and 1 had a grade 4 rectal complication. These numbers correspond to an estimated 0.7% (95% confidence interval, 0.0-1.6%) of patients experiencing a grade 3 or 4 complication by 5 years after the start of EBRT.

Conclusions

Salvage EBRT for a detectable PSA level after RP is the only curative treatment in this setting. This treatment can be administered in a manner that results in a low likelihood of late complications.     

Volumetric modulated arc therapy versus conventional intensity modulated radiation therapy for stereotactic spine radiotherapy: A planning study and early clinical data

Background and purpose

Outcomes for selected patients with spinal metastases may be improved by dose escalation using stereotactic body radiation therapy (SBRT). As target geometry is complex, we compared SBRT plans using volumetric modulated arc radiotherapy (RapidArc®, RA) and conventional intensity-modulated radiotherapy (IMRT).

Materials and methods

RA and IMRT plans to deliver a fraction of 16 Gy to at least 90% of planning target volume (PTV) were compared for PTV coverage, normal organ sparing and estimated delivery times. Group 1 consisted of PTVs to only vertebral body (n = 3), while group 2 had PTVs encompassing the entire vertebra (n = 4). Finally, RA delivery parameters in four patients were assessed.

Results

Both techniques delivered 16 Gy to a mean of 95% and 85% of the PTV in groups 1 and 2, respectively. Spinal cord sparing was comparable; mean V_{10-partial cord} for RA and IMRT in group 1 was 3.6%, and was 9.4% versus 11.5%, respectively, in group 2. Estimated mean treatment times for RA with 2-3 arcs and IMRT were comparable. Clinical RA beam-on times ranged from 11 to 15.4 min.

Conclusions

Both RA and conventional IMRT plans deliver high quality vertebral SBRT, but plan quality was poorer when the PTV consisted of the entire vertebra.     

A significant decrease in rectal volume and diameter during prostate IMRT

Purpose

To record changes in rectal volume (RV) and diameter (RD) of patients with prostate adenocarcinoma prior to and at an interim period during radiotherapy, which could potentially affect treatment toxicity and tumor control.

Methods

Three hundred and fifteen patients treated with intensity modulated radiotherapy (IMRT) underwent planning CT scans before radiation and after 45 Gy. For each scan, RV and RD were recorded and compared using a two-tailed paired t-test. Robust linear regression analysis assessed correlation between initial RV and percent RV change.

Results

The mean change in RV was −8.62 cm³ and in RD was −0.19 cm³, (p < 0.05). A decrease ?10% in RV and RD was seen in 159 patients (50.5%) and 117 patients (37.1%), respectively. Patients with ?10% volume change had larger initial RVs than those with <10% decrease, (78.1 vs. 50.8 cm³, p < 0.0001).

Conclusions

A significant decrease in RV and RD occurs during prostate IMRT delivery. More than half of patients had decreased RV and over a third had decreased RD. This observation is pertinent to prostate localization, planning margins, and implies that dose-volume histogram (DVH) analysis of rectal irradiation based on pre-treatment CT scanning may inaccurately estimate the risk of rectal toxicity when the initial RV is larger than 70 cm³.     

Concomitant intensity modulated boost during whole breast hypofractionated radiotherapy - A feasibility and toxicity study

Background

Breast cancer sensitivity to large fraction size may be enhanced using hypofractionated concomitant boost radiotherapy (CBRT), thereby shortening overall treatment time. This ethics approved, prospective single cohort feasibility study was designed to evaluate the dosimetry and toxicity of CBRT using an intensity-modulated radiotherapy (IMRT) technique, compared with a standard sequential boost technique (SBT).

Methods

Fifteen women (11 right-sided; 4 left-sided) received 42.4 Gy to the whole breast and an additional 10.08 Gy to the tumor bed in 16 daily fractions, using IMRT and standard dose constraints. Each patient was replanned with the SBT, using mixed photon-electrons. Clinical target volume (CTV), dose evaluation volume (DEV), and organs at risk (OAR) dose distributions were compared with the SBT. Toxicity and treatment times were prospectively recorded.

Results

All 15 CBRT plans achieved the desired CTV (V_49.9Gy ? 99%) and DEV (V_49.9Gy ? 95%), coverage of the boost, compared with only 10 (66.7%, p = 0.03), and 12 (80%, p = 0.125) SBT plans, respectively. Ipsilateral lung (p < 0.0001), and heart (right-sided, p = 0.001; left-sided, p = 0.13) doses were lower. Grade 3 acute toxicity occurred in 1 (6.7%) patient. At 1 year, two (13.3%) additional patients had overall grade 2 late toxicity, compared with baseline. No grade 3-4 late toxicity was observed.

Conclusions

CBRT using IMRT improved boost coverage and lowered OAR doses, compared with SBT. Toxicities were acceptable using a daily boost of 3.28 Gy. While resource utilization was greater, overall treatment time was reduced.     

Pulmonary toxicity following IMRT after extrapleural pneumonectomy for malignant pleural mesothelioma

Background and purpose

The combination of chemotherapy, surgery, and radiotherapy has improved the prognosis for patients with malignant pleural mesothelioma (MPM). Intensity-modulated radiotherapy (IMRT) has allowed for an increase in dose to the pleural cavity and a reduction in radiation doses to organs at risk. The present study reports and analyses the incidence of fatal pulmonary toxicity in patients treated at Rigshospitalet, Copenhagen.

Materials and methods

Twenty-six patients were treated with induction chemotherapy followed by extrapleural pneumonectomy and IMRT between April 2003 and April 2006. The entire preoperative pleural surface area was treated to 50 Gy and areas with residual disease or close surgical margins were treated to 60 Gy in 30 fractions.

Results

The main toxicities were nausea, vomiting, esophagitis, dyspnea, and thrombocytopenia. One patient died from an intracranial hemorrhage during severe thrombocytopenia. Four patients (15%) experienced grade 5 lung toxicity, i.e. pneumonitis 19-40 days after the completion of radiotherapy. Patients with pneumonitis had a significantly larger lung volume fraction receiving 10 Gy or more (V10) (median: 60.3%, range 56.4-83.2%) compared to patients without pneumonitis (median: 52.6%, range: 25.6-80.3%) (p = 0.02). Mean lung dose (MLD) was also significantly higher in patients who developed pneumonitis (median 13.9 Gy, range: 13.6-14.2 Gy) than in patients who did not (median = 12.4 Gy, range: 8.4-15.4 Gy) (p = 0.04).

Conclusions

Significant differences in MLD and V10 for patients with fatal pulmonary toxicity compared to patients without fatal lung toxicity have been demonstrated. Based on the presented data local lung dose constraints have been modified in order to avoid unacceptable toxicity.     

A randomised controlled trial of forward-planned radiotherapy (IMRT) for early breast cancer: Baseline characteristics and dosimetry results

Background and purpose

This large trial was designed to investigate whether correction of dose inhomogeneities using intensity-modulated radiotherapy (IMRT) reduces late toxicity and improves quality of life in patients with early breast cancer. This paper reports baseline characteristics of trial participants and dosimetry results.

Materials and methods

Standard tangential plans of 1145 trials were analysed. Patients with inhomogeneous plans, defined by ICRU recommendations, were randomised to forward-planned IMRT or standard radiotherapy.

Results

Twenty-nine percentage of patients had adequate dosimetry with standard 2D radiotherapy. In the randomised patients, the decreases in mean volumes receiving greater than 107% (Vol > 107) and less than 95% (Vol < 95) of the prescribed dose in the IMRT compared with the control group were 34.0 cm³ (95% CI 26.4-41.6; P < 0.0001) and 48.1 cm³ (95% CI 34.4-61.9; P < 0.0001), respectively. In this study, 90% of patients who had a breast separation greater ?21 cm had Vol > 107 > 2 cm³ on standard radiotherapy plans.

Conclusion

This large trial, in which patients with all breast sizes were eligible, confirmed that breast dosimetry can be significantly improved with a simple method of forward-planned IMRT and has little impact on radiotherapy resources. It is shown that patients with larger breasts are more likely to have dose inhomogeneities and breast separation gives some indication of this likelihood. Photographic assessment of patients at 2 years after radiotherapy, as the next part of this randomised controlled trial, will show whether these results for IMRT translate into improved cosmetic outcome in patients with early breast cancer. This would provide impetus for the widespread adoption of 3D planning and IMRT.     

Hypofractionated intensity-modulated arc therapy for lymph node metastasized prostate cancer: Early late toxicity and 3-year clinical outcome

Background and purpose

For patients with N1 prostate cancer (PCa) aggressive local therapies can be advocated. We evaluated clinical outcome, gastro-intestinal (GI) and genito-urinary (GU) toxicity after intensity modulated arc radiotherapy (IMAT) + androgen deprivation (AD) for N1 PCa.

Material and methods

Eighty patients with T1-4N1M0 PCa were treated with IMAT and 2–3 years of AD. A median dose of 69.3 Gy (normalized isoeffective dose at 2 Gy per fraction: 80 Gy [α/β = 3]) was prescribed in 25 fractions to the prostate. The pelvic lymph nodes received a minimal dose of 45 Gy. A simultaneous integrated boost to 72 Gy and 65 Gy was delivered to the intraprostatic lesion and/or pathologically enlarged lymph nodes, respectively.GI and GU toxicity was scored using the RTOG/RILIT and RTOG-SOMA/LENT-CTC toxicity scoring system respectively. Three-year actuarial risk of grade 2 and 3/4 GI–GU toxicity and biochemical and clinical relapse free survival (bRFS and cRFS) were calculated with Kaplan–Meier statistics.

Results

Median follow-up was 36 months. Three-year actuarial risk for late grade 3 and 2 GI toxicity is 8% and 20%, respectively. Three-year actuarial risk for late grade 3–4 and 2 GU toxicity was 6% and 34%, respectively. Actuarial 3-year bRFS and cRFS was 81% and 89%, respectively. Actuarial 3-year bRFS and cRFS was, respectively 26% and 32% lower for patients with cN1 disease when compared to patients with cN0 disease.

Conclusion

IMAT for N1 PCa offers good clinical outcome with moderate toxicity. Patients with cN1 disease have poorer outcome.     

Urethral stricture following high dose rate brachytherapy for prostate cancer

Purpose

To evaluate the incidence, timing, nature and outcome of urethral strictures following high dose rate brachytherapy (HDRB) for prostate carcinoma.

Methods and materials

Data from 474 patients with clinically localised prostate cancer treated with HDRB were analysed. Ninety percent received HDRB as a boost to external beam radiotherapy (HDRBB) and the remainder as monotherapy (HDRBM). Urethral strictures were graded according to the Common Terminology Criteria for Adverse Events v3.0.

Results

At a median follow-up of 41 months, 38 patients (8%) were diagnosed with a urethral stricture (6-year actuarial risk 12%). Stricture location was bulbo-membranous (BM) urethra in 92.1%. The overall actuarial rate of grade 2 or more BM urethral stricture was estimated at 10.8% (95% CI 7.0-14.9%), with a median time to diagnosis of 22 months (range 10-68 months). All strictures were initially managed with either dilatation (n = 15) or optical urethrotomy (n = 20). Second line therapy was required in 17 cases (49%), third line in three cases (9%) and 1 patient open urethroplasty (grade 3 toxicity). Predictive factors on multivariate analysis were prior trans-urethral resection of prostate (hazard ratio (HR) 2.81, 95% CI 1.15-6.85, p = 0.023); hypertension (HR 2.83, 95% CI 1.37-5.85, p = 0.005); and dose per fraction used in HDR (HR for 1 Gy increase per fraction 1.33, 95% CI 1.08-1.64, p = 0.008).

Conclusions

BM urethral strictures are the most common late grade 2 or more urinary toxicity following HDR brachytherapy for prostate cancer. Most are manageable with minimally invasive procedures. Both clinical and dosimetric factors appear to influence the risk of stricture formation.     

Stereotactic radiotherapy with real-time tumor tracking for non-small cell lung cancer: Clinical outcome

Purpose

To report the clinical outcome of treatment using real-time tumor tracking for 70 patients with inoperable stage I non-small cell lung cancer (NSCLC).

Materials and methods

Seventy inoperable patients with peripherally located early-stage NSCLC were treated with 45 or 60 Gy in three fractions using CyberKnife. Pathology was available in 51% of patients. Thirty-nine patients had a T1-tumor and 31 had a T2-tumor. Markers were placed using the vascular, percutaneous intra-, or extra-pulmonary approach, depending on the risk of pneumothorax.

Results

The actuarial 2-year local control rate for patients treated with 60 Gy was 96%, compared to 78% for patients treated with a total dose of 45 Gy (p = 0.197). All local recurrences (n = 4) occurred in patients with T2-tumors. Overall survival for the whole group at two years was 62% and the cause specific survival was 85%. The median follow-up was 15 months. Grade 3 toxicity occurred in two patients (3%) after marker placement. Treatment-related late grade 3 toxicity occurred in 7 patients (10%). No grade ?4 toxicity occurred.

Conclusion

Excellent local control of 96% at 1- and 2-years was achieved using 60 Gy in three fractions for NSCLC patients treated with the real-time tumor tracking. Toxicity was low.     

Early pulmonary toxicity following lung stereotactic body radiation therapy delivered in consecutive daily fractions

Background and purpose

Identify the incidence of early pulmonary toxicity in a cohort of patients treated with lung stereotactic body radiation therapy (SBRT) on consecutive treatment days.

Material and methods

A total of 88 lesions in 84 patients were treated with SBRT in consecutive daily fractions (Fx) for medically inoperable non-small cell lung cancer or metastasis. The incidence of pneumonitis was evaluated and graded according to the NCI CTCAE v3.0.

Results

With a median follow-up of 15.8 months (range 2.5-28.6), the median age at SBRT was 71.8 years (range 23.8-87.8). 47 lesions were centrally located and 41 were peripheral. Most central lesions were treated with 48 Gy in 4 Fx, and most peripheral lesions with 54 Gy in 3 Fx. The incidence of grade ?2 pneumonitis was 12.5% in all patients treated, and 14.3% among the subset of patients treated with 54 Gy in 3 Fx. A total of two grade 3 toxicities were seen as one grade 5 toxicity in a patient treated for recurrence after pneumonectomy.

Conclusions

Treating both central and peripheral lung lesions with SBRT in consecutive daily fractions in this cohort was well tolerated and did not cause excessive early pulmonary toxicity.     

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.     

Second re-irradiation: Efficacy, dose and toxicity in patients who received three courses of radiotherapy with overlapping fields

Purpose

To explore the outcome, cumulative dose and toxicity in 23 patients after a third radiation treatment, with a partial or complete overlap of the previous two irradiated regions.

Methods and material

The dose summation of the three radiation plans was made by the planning system. For patients treated with cyberknife or brachytherapy dose summation was done by dose point calculations. Efficacy and toxicity was scored by looking at the reduction of tumor, pain and bleeding.

Results

Symptomatic response was observed in 81% and 73% of the patients after, respectively, the third and second radiation. The median cumulative maximum dose to the tumor and its regions was 133 Gy₃ (range: 82-496 Gy₃). The median corrected cumulative dose for the rectum, bowel and bladder resulted in 91 Gy₃, 73 Gy₃ and 79 Gy₃, respectively. Grade 3 acute skin toxicity was only seen in the third radiation course.

Conclusion

The constraints of 100 Gy₃ for rectum, 90 Gy₃ for bowel and 110 Gy₃ for bladder are safe and can be used as guidelines in the decision for re-irradiation. Symptomatic relieve was seen in 81% of the patients with low grade 3 and no grade 4 acute and late toxicity.     

Comparison of intensity-modulated radiotherapy, adaptive radiotherapy, proton radiotherapy, and adaptive proton radiotherapy for treatment of locally advanced head and neck cancer

Background and purpose

Various radiotherapy planning methods for locally advanced squamous cell carcinoma of the head and neck (SCCHN) have been proposed to decrease normal tissue toxicity. We compare IMRT, adaptive IMRT, proton therapy (IMPT), and adaptive IMPT for SCCHN.

Materials and methods

Initial and re-simulation CT images from 10 consecutive patients with SCCHN were used to quantify dosimetric differences between photon and proton therapy. Contouring was performed on both CTs, and plans (n = 40 plans) and dose-volume histograms were generated.

Results

The mean GTV volume decreased 53.4% with re-simulation. All plans provided comparable PTV coverage. Compared with IMRT, adaptive IMRT significantly reduced the maximum dose to the mandible (p = 0.020) and mean doses to the contralateral parotid gland (p = 0.049) and larynx (p = 0.049). Compared with IMRT and adaptive IMRT, IMPT significantly lowered the maximum doses to the spinal cord (p < 0.002 for both) and brainstem (p < 0.002 for both) and mean doses to the larynx (p < 0.002 for both) and ipsilateral (p = 0.004 IMRT, p = 0.050 adaptive) and contralateral (p < 0.002 IMRT, p = 0.010 adaptive) parotid glands. Adaptive IMPT significantly reduced doses to all critical structures compared with IMRT and adaptive IMRT and several critical structures compared with non-adaptive IMPT.

Conclusions

Although adaptive IMRT reduced dose to several normal structures compared with standard IMRT, non-adaptive proton therapy had a more favorable dosimetric profile than IMRT or adaptive IMRT and may obviate the need for adaptive planning. Protons allowed significant sparing of the spinal cord, parotid glands, larynx, and brainstem and should be considered for SCCHN to decrease normal tissue toxicity while still providing optimal tumor coverage.     

Anatomical and clinical predictors of acute bowel toxicity in whole pelvis irradiation for prostate cancer with Tomotherapy

Purpose

Assessing predictors of acute bowel toxicity after whole-pelvis irradiation (WPRT) Image-guided Tomotherapy with simultaneous integrated boost on prostate/prostate bed.

Methods and materials

In the period March 2005-April 2009, 178 patients were treated with radical or adjuvant/salvage intent with WPRT Tomotherapy. Median dose to the pelvic nodes was 51.8 Gy/28 fractions while concomitantly delivering 65.5-74.2 Gy to prostate/prostatic bed. The impact of many anatomical and clinical parameters on ?Grade 2 acute bowel toxicity was investigated by logistic analyses.

Results

Only 15/178 patients (8.4%) experienced Grade 2 toxicity (none Grade 3). Main predictors at univariate analysis were nodal CTV (CTVN ? 380 cc; OR: 3.7, p = 0.017), treatment duration (<40 days; OR: 6.2, p = 0.006) and Grade 2 acute rectal toxicity (OR: 6.5, p = 0.015). A multivariate analysis including only pre-treatment variables revealed an independent role of CTVN and age; if including treatment-related factors the best predictors were age, treatment duration and Grade 2 rectal toxicity. This last was correlated with the overlap between PTVN and loops (OVPN ? 51 cc; OR: 14.4, p = 0.0003) that is representative of the volume of loops receiving the prescribed dose (51.8 Gy, 1.85 Gy/fr).

Conclusions

Acute bowel toxicity after WPRT Tomotherapy is mild, relatively rare and associated to larger CTVN and older age. While efforts to further reduce it do not appear to be relevant, the pre-treatment assessment of “high-risk” patients may help physicians in better managing symptoms. A prospective validation would be very important in confirming these results and in better refining dose-volume bowel effects including symptoms milder that the ones here investigated and retrospectively assessed.     

Impact of target volumes and radiation technique on loco-regional control and survival for patients with unilateral cervical lymph node metastases from an unknown primary

Purpose

To compare the impact of an unilateral post-operative irradiation or a bilateral irradiation in terms of loco-regional control and survival in patients with cervical lymph node of squamous cell carcinoma from an unknown primary (CUP).

Methods and materials

Ninety five patients with epidermoid carcinoma involving unilateral cervical lymph nodes from an unknown primary were treated in two institutions from 1990 to 2007. Post-operative radiation therapy was delivered to one side of the neck in 59 cases, to both sides of the neck in 36 cases. There were 11 women and 84 men ranging in age from 38 to 80 years (median 59 years). Neck dissection was performed in 79 patients while 16 patients underwent single lymph node sampling only.

Results

After a median follow-up of 3.3 years, the nodal relapse rate was 34% after unilateral neck irradiation and 25% after bilateral radiotherapy (p = 0.21). Six contralateral lymph node relapses occurred after unilateral irradiation (10%). The 5-year overall survival rate of the entire group was 24%. The 5-year OS rates were 22% after unilateral irradiation and 23%, after bilateral radiotherapy (p = 0.944). The occult primary occurred in 12% after unilateral irradiation and 6% after bilateral radiotherapy. The radiation technique (3D-CRT or IMRT vs. 2D: p = 0.026) was prognostic on loco-regional control. Independent prognostic determinants on overall survival were the WHO status (p = 0.013) and the radiation technique (2D vs. 3D-CRT or IMRT; p = 0.029). There was no difference in loco-regional control (p = 0.639) and no difference in survival (p = 0.493) when chemotherapy was associated.

Conclusions

Retrospective comparisons between bilateral and unilateral neck radiotherapies did not show differences in terms of loco-regional control and survival. However, patient’s local regional control and survival are significantly improved after 3D-CRT or IMRT.