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.     

The Cancer of the Prostate Risk Assessment (CAPRA) in patients treated with external beam radiation therapy: Evaluation and optimization in patients at higher risk of relapse

Background

The Cancer of the Prostate Risk Assessment (CAPRA) was developed to predict freedom from biochemical failure (FFBF) following radical prostatectomy (RP). Its utility following external beam radiation therapy (EBRT) has not been externally evaluated.

Methods

A retrospective study of 612 patients treated with dose-escalated EBRT at the University of Michigan Medical Center.

Results

Compared to the derivation cohort, EBRT treated patients had higher-risk disease (28% with CAPRA of 6-10 vs. 5%, respectively). A total of 114 patients (19%) had BF with 5-year BF ranging from 7% with CAPRA 0-3 to 35% with CAPRA 7-10. For RT patients the risk of BF at 5-year was similar to 4 surgical cohorts for CAPRA scores 0-2 but lower for all CAPRA scores ? 3. The difference favoring RT increased with increasing CAPRA score reaching a 27-50% absolute improved at 5-years for CAPRA scores of 6-10. On multivariate analysis each CAPRA point increased the risk of BF (p < 0.0001) while Gleason pattern 5 in the biopsy also increased BF (p = 0.01) and long-term androgen deprivation therapy (ADT) significantly reduced the risk of BF (p = 0.015).

Conclusions

Compared to surgical series the risk of BF was lower with dose-escalated EBRT with the greatest difference at the highest CAPRA scores.     

Development and validation of a nomogram for prediction of survival and local control in laryngeal carcinoma patients treated with radiotherapy alone: A cohort study based on 994 patients

Introduction

To advise laryngeal carcinoma patients on the most appropriate form of treatment, a tool to predict survival and local control is needed.

Materials and methods

We performed a population-based cohort study on 994 laryngeal carcinoma patients, treated with RT from 1977 until 2008. Two nomograms were developed and validated. Performance of the models is expressed as the Area Under the Curve (AUC).

Results

Unfavorable prognostic factors for overall survival were low hemoglobin level, male sex, high T-status, nodal involvement, older age, lower EQD_2T (total radiation dose corrected for fraction dose and overall treatment time), and non-glottic tumor. All factors except tumor location were prognostic for local control. The AUCs were 0.73 for overall survival and 0.67 for local control. External validation of the survival model yielded AUCs of 0.68, 0.74, 0.76 and 0.71 for the Leuven (n = 109), the VU Amsterdam (n = 178), the Manchester (n = 403) and the NKI cohort (n = 205), respectively, while the validation procedure for the local control model resulted in AUCs of 0.70, 0.71, 0.72 and 0.62. The resulting nomograms were made available on the website www.predictcancer.org.

Conclusions

For patients with a laryngeal carcinoma treated with RT alone, we have developed visual, easy-to-use nomograms for the prediction of overall survival and primary local control. These models have been successfully validated in four external centers.     

Parotid gland as a risk organ in whole brain radiotherapy

Background and purpose

Since the introduction of CT-based simulation for use in whole brain radiotherapy (WBRT), we have observed that a large volume of the parotid glands is included in the radiation fields. The purpose of this study is to analyze the dose-volume statistics of the parotid glands in patients undergoing WBRT.

Materials and methods

Thirty-two patients received WBRT using CT-based simulation with bilateral two-field arrangement. Daily fraction was 3 Gy with total dose of 30 Gy in 2 weeks. We analyzed the radiation dose from WBRT to the parotid glands.

Results

Average of the mean parotid dose was 17.5 Gy (range, 10.5-26.2) for both glands. Mean parotid doses ?20 and ?25 Gy were observed in 22 (34.4%) and 4 (6.3%) of 64 individual glands. The numbers of patients with a mean parotid dose of both glands ?20 Gy and ?25 Gy were 12 (37.5%) and 1 (3.1%), respectively.

Conclusions

Mean parotid dose was variable in patients with WBRT. According to the parotid dose and combined potential risk factors, parotid glands can be regarded as a risk organ in WBRT for improvement of patient quality of life.     

Outcomes following iodine-125 prostate brachytherapy with or without neoadjuvant androgen deprivation

Purpose

To report the biochemical failure-free survival (BFFS), cause-specific survival (CSS), and overall survival (OS) outcomes of patients treated with iodine-125 (I-125) brachytherapy for clinically localized prostate cancer.

Methods and materials

Between 2003 and 2009, I-125 permanent prostate brachytherapy without supplemental external-beam radiotherapy was performed for 663 patients with low-risk and low-tier intermediate-risk (defined as organ-confined disease, PSA <10 ng/mL, and Gleason score 3 + 4 with biopsy positive core rate <33%) prostate cancer. Early in the study period, the preplanning method was used in the first 104 patients, and later the real-time planning method was used. Biochemical failure was determined using the American Society for Therapeutic Radiology Oncology (ASTRO) and Phoenix definitions.

Results

The 7-year BFFS rates for the ASTRO and Phoenix definitions were 96.1% and 95.9%, respectively. The corresponding BFFS rates by risk group were 97.6% and 96.7% for low-risk, and 91.8% and 93.6% for low-tier intermediate-risk disease (p = 0.007 and 0.08, respectively). The median times to biochemical failure in those who failed were 29.5 and 43.9 months according to the ASTRO and Phoenix definitions, respectively. The 7-year CSS and OS were 99.1% and 96.4%. There was no significant difference in CSS or OS between the low-risk and low-tier intermediate-risk groups. In multivariate Cox regression analysis, risk group and prostate D90 were independent predictors of BFFS for the ASTRO definition, while only the prostate D90 was significant for the Phoenix definition.

Conclusion

I-125 prostate brachytherapy results in excellent 7-year BFFS, CSS, and OS for low-risk and low-tier intermediate-risk prostate cancer.     

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.     

Young age under 60 years is not a contraindication to treatment with definitive dose escalated radiotherapy for prostate cancer

Background

It is widely believed that younger prostate cancer patients are at greater risk of recurrence following radiotherapy (RT).

Methods

From 1992 to 2007, 2168 (395 age ?60) men received conformal RT alone for prostate cancer at our institution (median dose = 76 Gy, range: 72-80). Multivariable analysis (MVA) was used to identify significant predictors for BF and PCSM. Cumulative incidence was estimated using the competing risk method (Fine and Gray) for BF (Phoenix definition) and PCSM to account for the competing risk of death.

Results

With a median follow-up of 72.2 months (range: 24.0-205.1), 8-year BF was 27.1% for age ?60 vs. 23.7% for age >60 (p = 0.29). Eight-year PCSM was 3.0% for age ?60 vs. 2.0% for age >60 (p = 0.52). MVA for BF identified initial PSA [adjusted HR = 1.7 (PSA 10-20), 2.6 (PSA >20), p < 0.01], Gleason score [adjusted HR = 2.1 (G7), 1.9 (G8-10), p < 0.01], T-stage [adjusted HR = 1.7 (T2b-c), 2.6 (T3-4), p < 0.01], and initial androgen deprivation therapy (ADT) [adjusted HR = 0.38 (ADT >12 months), p < 0.01] as significant, but not age or ADT <12 months. MVA for PCSM identified Gleason score [adjusted HR = 3.0 (G8-10), p = 0.01] and T-stage [adjusted HR = 8.7 (T3-4), p < 0.01] as significant, but not age, PSA, or ADT.

Conclusion

This is the largest, most mature study of younger men treated with RT for prostate cancer that confirms young age is not prognostic for BF.     

Outcomes from Gleason 7, intermediate risk, localized prostate cancer treated with Iodine-125 monotherapy over 10 years

Background and purpose

The effect of predominating Gleason grade (3 + 4 versus 4 + 3) in Gleason sum score (GS) 7 prostate cancer (PCa) on brachytherapy outcomes is unclear. The 10 year experience of permanent brachytherapy monotherapy at a single UK centre for GS 7, intermediate risk (Memorial Sloan-Kettering model), PSA ? 10 ng/ml, localised PCa is reported.

Materials and methods

Between 1995 and 2004, the outcomes of 187 patients with GS 7 PCa (PSA ? 10 ng/ml) were analysed from a cohort of 1298 men treated with permanent Iodine-125 prostate brachytherapy, including PSA relapse-free survival (PSA-RFS).

Results

Median follow-up was 5.0 years (range 2.0-10.1 years). One patient has died of PCa. At 10 years, PSA-RFS was 82.4%/78% (ASTRO consensus and nadir +2 definitions). For GS 3 + 4, 5 year PSA-RFS was 86.7%/87.9% and for GS 4 + 3: 85.2%/96.6% respectively, with no significant difference between groups. Five year PSA-RFS (ASTRO) of 92.6% was seen for D₉₀ ? 140 Gy (50% total), compared with 77.0% below 140 Gy (p = 0.08).

Conclusions

Iodine-125 brachytherapy monotherapy achieved good rates of medium term biochemical control in GS 7, intermediate risk localised PCa patients. There was a trend to improved outcomes in men with a D90 in excess of 140 Gy.     

Characterization and outcomes of infratentorial malignant glioma: A population-based study using the Surveillance Epidemiology and End-Results database

Purpose

Using a population-based database, we sought to characterize brainstem gliomas and to evaluate the prognosis of various subgroups.

Materials and methods

Using the Surveillance Epidemiology and End-Results (SEER) database we identified patients diagnosed with malignant infratentorial gliomas between 1988 and 2003 who underwent a surgical procedure and/or received radiation therapy (RT).

Results

A total of 455 patients were identified with a median age at diagnosis of 13 years (range 0-87). The overwhelming majority, 95.6%, received RT. Median survival (MS) was 11 months. Those not undergoing RT had a MS of 3 months. MS varied significantly by age, p < 0.001. MS for patients aged 0-18 years was 11 months; 19-29 years was 35 months; 30-49 years was 17 months; 50-69 years was 6 months; and 70 years or older was 3 months. The small group with grades I and II tumors had improved MS of 58 and 37 months, respectively. There was no difference in survival by the year of diagnosis (?1999 versus 2000 or later) with MS of 10 versus 11 months, respectively, p = 0.949.

Conclusion

Brainstem glioma is primarily a childhood malignancy with a generally poor prognosis. A minority of patients has favorable features and can achieve long-term survival.     

Stereotactic body radiation therapy for lung metastases

Introduction

Stereotactic body radiation therapy (SBRT) has an emerging role in patients affected with pulmonary metastases. Purpose of this study was to evaluate efficacy and tolerability of SBRT in a cohort of patients treated between 2003 and 2009 at our institution.

Methods

A total of 61 patients with oligometastatic lung tumors (single pulmonary nodules in 73.7%) were included in the study. SBRT was performed with a stereotactic body frame and a 3D-conformal technique. Fifty-one patients received 26 Gy in 1 fraction, 22 a dose of 45 Gy in 3 fractions and 3 a dose of 36 Gy in 4 fractions. Primary tumor was lung cancer in 45.7% of patients, colorectal cancer in 21.3% and a variety of other origins in 33%. The primary endpoint was local control, secondary endpoints were survival and toxicity.

Results

After a median follow-up interval of 20.4 months, local control rates at 2 and 3 years were 89% and 83.5%, overall survival 66.5% and 52.5%, cancer-specific survival 75.4% and 67%, progression-free survival 32.4% and 22.3%. Tumor volume was significantly associated to survival, with highest rates in patients with single small tumors. Median survival time was 42.8 months, while median progression-free survival time was 11.9 months. Toxicity profiles were good, with just one case of grade III toxicity (pneumonitis).

Conclusion

This study shows that SBRT is an effective and safe local treatment option for patients with lung metastases. Definitive results are strictly correlated to clinical selection of patients.     

Correlation between dose to the pharyngeal constrictors and patient quality of life and late dysphagia following chemo-IMRT for head and neck cancer

Purpose

Aim of this study was to correlate dose to pharyngeal constrictors (PC) with subjective and observer-based assessments of swallowing in patients with head and neck cancer undergoing concomitant chemo-IMRT.

Materials and methods

Dose-volume histograms (DVHs) for superior constrictor (SC), middle constrictor (MC) and inferior constrictor (IC) were generated for 37 patients. Mean doses to SC, MC and IC were correlated to objective dysphagia grade (1 year, RTOG scoring) and global, total physical (TP) and most relevant components of the physical section (P6, P8) of the MD Anderson dysphagia inventory (MDADI) which was evaluated post-treatment. Odds ratios of dysphagia (>grade 0), poor global (<3), TP (<32), P6 (<3) and P8 (<3) for patients with mean dose > 60 Gy to SC and IC were calculated.

Results

There was no significant correlation between mean dose to PC and any of the analysed MDADI parameters and observer-assessed dysphagia grade. Odds ratio of dysphagia (>grade 0), poor global (<3), TP (<32), P6 (<3) and P8 (<3) for patients with mean dose > 60 Gy to IC and SC were not significantly higher than those for patients receiving <60 Gy.

Conclusion

This study did not find a statistically significant correlation between radiation dose to the PC and observer-assessed dysphagia grade or patient-reported MDADI questionnaire at 1 year.     

Biochemical outcomes for patients with intermediate risk prostate cancer treated with I-125 interstitial brachytherapy monotherapy

Background and purpose

Routine use of I-125 interstitial brachytherapy (BT) alone in intermediate risk (IR) prostate cancer is controversial. It is often combined with external beam radiotherapy (EBRT). The biochemical outcome of a large cohort of only IR disease treated with BT monotherapy is reported.

Materials and methods

Between 2003 and 2007, 615 patients with Memorial Sloan-Kettering Cancer Centre (MSKCC) defined IR disease (one risk factor only-T2b, or Gleason score (GS) 7, or raised initial PSA (iPSA) 10.1–20 ng/ml) were treated with BT monotherapy. ASTRO (3 consecutive rises) and Phoenix (nadir plus 2) criteria defined biochemical failure. Potential prognostic factors (pre- and post-implant dosimetric indices, GS 3 + 4 versus 4 + 3, androgen deprivation therapy (ADT)) were analysed.

Results

Median follow-up was 5.0 years. Forty-three patients had stage T2b, 180 had raised iPSA, 392 had GS 7 disease. ADT was received by 108 patients. The 5-year biochemical no evidence of disease (bNED) rates are 87.3% (by ASTRO), 88.6% (by Phoenix). Stratification by risk factor (T2b, GS7, raised iPSA) demonstrated raised iPSA to have poorer outcome only by Phoenix criteria (p = 0.0002). Other potential prognostic variables were non-significant.

Conclusion

Good rates of biochemical control can be achieved in the medium term with BT monotherapy in IR disease. Raised iPSA correlated with a poorer outcome.     

Toxicity after reirradiation of pulmonary tumours with stereotactic body radiotherapy

Purpose

To assess toxicity and feasibility of reirradiation with stereotactic body radiotherapy (SBRT) after prior lung SBRT for primary lung cancer or lung metastases.

Patients and materials

Twenty-nine patients reirradiated with SBRT on 32 lung lesions (11 central, 21 peripheral) were retrospectively reviewed. Median follow-up time was 12 months (range 1-97). The primary endpoint was toxicity, secondary endpoints were local control and overall survival time. Toxicity was scored according to the NCI-CTCAE version 3.

Results

Grade 3-4 toxicity was scored 14 times in eight patients. Three patients died because of massive bleeding (grade 5). Larger clinical target volumes (CTV) and central tumour localization were associated with more severe toxicity. There was no correlation between mean lung dose (MLD) and lung toxicity. Local control at 5 months after reirradiation was 52%, as assessed by CT-scan (n = 12) or X-thorax (n = 3). A larger CTV was associated with poorer local control. Kaplan-Meier estimated 1- and 2-year survival rates were 59% and 43%, respectively.

Conclusions

Reirradiation with SBRT is feasible although increased risk of toxicity was reported in centrally located tumours. Further research is warranted for more accurate selection of patients suitable for reirradiation with SBRT.     

Motion-weighted target volume and dose-volume histogram: A practical approximation of four-dimensional planning and evaluation

Background and purpose

In ITV-based 3D-planning, the information of volume occupancy versus respiratory phase is not utilized. We propose a motion-weighted CTV (mwCTV) delineation method, which carries some 4D-information into planning. This method allows plan optimization based on occupancy-weighting and generation of motion-weighted DVH (mwDVH) that approximate the DVHs of full 4D-dose accumulation.

Material and methods

Occupancy information from contours in 4D-CT is incorporated in the mwCTV generation. Higher-occupancy volumes receive higher dosimetric priority in planning. The temporally-weighted mwCTV is converted to a spatially-weighted mwCTV incorporating the temporal-weighting in mwDVH generation using the 3D-dose distribution. The mwDVHs were compared with DVHs of deformable-image-registration (DIR)-based 4D-dose accumulation and 3D-method for 10 cases.

Results

For all the cases, the mwDVH curves are closer to the 4D-calculated DVH than the 3D-DVHs are, indicating a better approximation of the 4D-DVH. The 70 Gy-covered percentage-CTV volume differed by −2.8% ± 0.8% between 3D and 4D, and 0.3% ± 0.7% between mwDVH and 4D-methods. The mean RMS values of the percentage-volume differences for the 4D-3D is 1.7 ± 1.1, while for the 4D-mwDVH is 0.4 ± 0.3.

Conclusion

The mwCTV and mwDVH method, which is simple in implementation and does not require DIR, is a practical approximation of DIR-based 4D-planning and evaluation.     

Meta-analysis of chemotherapy in head and neck cancer (MACH-NC): An update on 93 randomised trials and 17,346 patients

Background

Our previous individual patient data (IPD) meta-analysis showed that chemotherapy improved survival in patients curatively treated for non-metastatic head and neck squamous cell carcinoma (HNSCC), with a higher benefit with concomitant chemotherapy. However the heterogeneity of the results limited the conclusions and prompted us to confirm the results on a more complete database by adding the randomised trials conducted between 1994 and 2000.

Methods

The updated IPD meta-analysis included trials comparing loco-regional treatment to loco-regional treatment + chemotherapy in HNSCC patients and conducted between 1965 and 2000. The log-rank-test, stratified by trial, was used to compare treatments. The hazard ratios of death were calculated.

Results

Twenty-four new trials, most of them of concomitant chemotherapy, were included with a total of 87 trials and 16,485 patients. The hazard ratio of death was 0.88 (p < 0.0001) with an absolute benefit for chemotherapy of 4.5% at 5 years, and a significant interaction (p < 0.0001) between chemotherapy timing (adjuvant, induction or concomitant) and treatment. Both direct (6 trials) and indirect comparisons showed a more pronounced benefit of the concomitant chemotherapy as compared to induction chemotherapy. For the 50 concomitant trials, the hazard ratio was 0.81 (p < 0.0001) and the absolute benefit 6.5% at 5 years. There was a decreasing effect of chemotherapy with age (p = 0.003, test for trend).

Conclusion

The benefit of concomitant chemotherapy was confirmed and was greater than the benefit of induction chemotherapy.     

Dosimetric evolution of the breast electron boost target using 3D ultrasound imaging

Purpose

To investigate the effect of treatment planning, patient setup, and interfraction motion errors on the delivered dose for external beam electron boosts for postoperative early stage breast cancer patients.

Methods and materials

For 5 patients, 10-15 Gy was prescribed and administered via a conventionally defined electron boost treatment field - no dose distribution was calculated. Two computed tomography (CT) data sets were acquired on an average of 47 days apart. Using Monte Carlo techniques the clinically defined electron beams were reconstructed on CT1 and CT2, and a dosimetric comparison between the two data sets was made. Additionally, 3D ultrasound (US) imaging was performed to monitor interfraction motion. 3D US images were acquired concurrently with the CT images, as well as prior to each boost fraction in the treatment room. Taking into account interfraction motion, the dose to the clinical target volume (CTV) was calculated.

Results

Based on conventionally determined treatment fields the CT1-based CTV D95 averaged 49% (range 12-89%) of the prescribed dose. Representing setup errors, the CT2-based CTV D95 averaged 47% (range 16-91%) of the prescribed dose. Considering interfraction motion, the average radial displacement was 11 mm, and the resulting CTV D95 was further reduced in 2/5 patients.

Conclusions

Poor initial coverage at the time of planning is exacerbated by breast mobility and interfraction tumour bed motion, increasing the uncertainty in the delivered dose.     

Three-dimensional conformal radiation therapy for squamous cell carcinoma of the esophagus: A prospective phase I/II study

Purpose

A prospective phase I-II study was conducted to determine the tolerance and local control rate of three-dimensional conformal radiotherapy (3-DCRT) for esophageal squamous cell carcinoma (SCC).

Methods and materials

Thirty patients underwent 3-DCRT for thoracic esophageal SCC. PTV1 composed of a 1.2-1.5 cm margin lateral around GTV and 3.0 cm margin superior/inferior of GTV. PTV2 encompassed GTV with a margin of 0.5-0.7 cm. The dose for PTV1 was 50 Gy in 2 Gy daily fractions; PTV2 received a boost of 16 Gy in 2 Gy daily fractions to a total dose of 66 Gy.

Results

Median follow-up time was 18 months. The most common acute toxicity was esophagitis in 63% of patients with RTOG grades 1-2, and in 3% with grade 3. RTOG grades 1-2 radiation pneumonitis developed in 27% of patients. One patient developed pulmonary fibrosis RTOG grade 2 and another patient experienced grade 3 pulmonary fibrosis. Two patients developed mild esophageal stricture requiring dilatation. Two-year overall survival, local disease progression-free rate, and distant metastasis-free rate were 69%, 36% and 56%, respectively.

Conclusions

Although 3-DCRT to 66 Gy for esophageal SCC was well tolerated, the local control was disappointing. The result supports the use of chemoradiation as the standard care for esophageal SCC.     

3D CT-based high-dose-rate brachytherapy for cervical cancer: Clinical impact on late rectal bleeding and local control

Background and purpose

To identify the impact of 3D CT-based high-dose-rate intracavitary radiotherapy (ICR) on late rectal bleeding (LRB) and local control (LC) in patients with cervical cancer.

Material and methods

The outcomes of 97 consecutive patients treated with 3D CT-based ICR (3D-ICR) were compared with those of 133 consecutive historical patients with conventional 2D brachytherapy planning (2D-ICR). The median follow-up periods were 41 and 56 months for the 3D and 2D groups, respectively.

Results

The overall rectal bleeding rate was similar between the groups (42% for 3D-ICR vs. 44% for 2D-ICR); however, the incidence of severe LRB was higher in the 2D-ICR group than in the 3D-ICR group (13% vs. 2%, respectively; p = 0.02). In multivariate analysis, the factors associated with severe LRB were tumor >4 cm (12% vs. 3%) and 2D-ICR (10% vs. 2%). The LC rates were 97% and 91% for 3D-ICR and 2D-ICR, respectively (p = 0.14); the progression-free survival rate was 80% for both groups. A significant difference in the LC rates between the two groups was observed in patients with larger tumor sizes with the tumor diameter of over 4 cm (98% vs. 81% by 3D-ICR vs. 2D-ICR, respectively; p = 0.02).

Conclusions

The implementation of 3D-ICR in radiotherapy for cervical cancer can reduce the incidence of severe LRB and may improve the LC rate.     

Evaluation of early metabolic responses in rectal cancer during combined radiochemotherapy or radiotherapy alone: Sequential FDG-PET-CT findings

Background and purpose

The purpose of this study was to prospectively investigate metabolic changes of rectal tumors after 1 week of treatment of either radiochemotherapy (28 × 1.8 Gy + Capecitabine) (RCT) or hypofractionated radiotherapy (5 × 5 Gy) alone (RT).

Materials and methods

Fourty-six rectal cancer patients, 25 RCT- and 21 RT-patients, were included in this study. Sequential FDG-PET-CT scans were performed for each of the included patients both prior to treatment and after the first week of treatment. Consecutively, the metabolic treatment response of the tumor was evaluated.

Results

For the patients referred for pre-operative RCT, significant reductions of SUV_mean (p < 0.001) and SUV_max (p < 0.001) within the tumor were found already after the first week of treatment (8 Gy biological equivalent dose (BED). In contrast, 1 week of treatment with RT alone did not result in significant changes in the metabolic activity of the tumor (p = 0.767, p = 0.434), despite the higher applied RT dose of 38.7 Gy BED.

Conclusions

Radiochemotherapy of rectal cancer leads to significant early changes in the metabolic activity of the tumor, which was not the case early after hypofractionated radiotherapy alone, despite the higher radiotherapy dose given. Thus, the chemotherapeutic agent Capecitabine might be responsible for the early metabolic treatment responses during radiochemotherapy in rectal cancer.     

A randomised phase II study of docetaxel/oxaliplatin and docetaxel in patients with previously treated non-small cell lung cancer: an Alpe-Adria Thoracic Oncology Multidisciplinary group trial (ATOM 019)

Introduction

To date, no combination regimen has proven superior to single agent chemotherapy as a second-line treatment for non-small cell lung cancer (NSCLC).

Methods

This multicenter, non-comparative randomised phase II trial evaluated the activity of docetaxel (75 mg/m² on day 1) with oxaliplatin (70 mg/m² on day 2) every 3 weeks in previously treated NSCLC patients; the reference arm was single-agent docetaxel (75 mg/m² on day 1 every 3 weeks). It was designed as a one-stage, three-outcome phase II trial; 21 evaluable patients were required in each arm. The primary end-point was response rate; secondary end-points were toxicity, progression free survival (PFS) and overall survival.

Results

Fifty patients were enrolled. Patient characteristics included male/female, 76/24%; median age 62 years; ECOG PS 0/1, 36/64%; previous platinum-based chemotherapy, 98%. Partial response was seen in 20% and 8%, stable disease in 52% and 32%, of patients treated with docetaxel/oxaliplatin and docetaxel, respectively. Main grade 3-4 toxicities were neutropenia 56% and 64%; febrile neutropenia 4% and 8%; diarrhoea 12% and 4% for docetaxel/oxaliplatin and docetaxel, respectively. Median PFS was 5.0 and 1.7 months, median survival 11.0 and 7.1 months, and 1-year survival 44% and 32% for docetaxel/oxaliplatin and docetaxel, respectively.

Conclusions

The study met its pre-defined study end-point; docetaxel/oxaliplatin and more generally platinum-containing doublets warrant further evaluation as second-line therapy for patients with NSCLC.