Breast-conserving therapy with partial or whole breast irradiation: Ten-year results of the Budapest randomized trial

Background and purpose

To report the long-term results of a single-institution randomized study comparing the results of breast-conserving treatment with partial breast irradiation (PBI) or conventional whole breast irradiation (WBI).

Patients and methods

Between 1998 and 2004, 258 selected women with pT1 pN0-1mi M0, grade 1–2, non-lobular breast cancer without the presence of extensive intraductal component and resected with negative margins were randomized after BCS to receive 50 Gy WBI (n = 130) or PBI (n = 128). The latter consisted of either 7 × 5.2 Gy high-dose-rate (HDR) multi-catheter brachytherapy (BT; n = 88) or 50 Gy electron beam (EB) irradiation (n = 40). Primary endpoint was local recurrence (LR) as a first event. Secondary endpoints were overall survival (OS), cancer-specific survival (CSS), disease-free survival (DFS), and cosmetic results.

Results

After a median follow up of 10.2 years, the ten-year actuarial rate of LR was 5.9% and 5.1% in PBI and WBI arms, respectively (p = 0.77). There was no significant difference in the ten-year probability of OS (80% vs 82%), CSS (94% vs 92%), and DFS (85% vs 84%), either. The rate of excellent-good cosmetic result was 81% in the PBI, and 63% in the control group (p < 0.01).

Conclusions

Partial breast irradiation delivered by interstitial HDR BT or EB for a selected group of early-stage breast cancer patients produces similar ten-year results to those achieved with conventional WBI. Significantly better cosmetic outcome can be achieved with HDR BT implants compared with the outcome after WBI.     

Radiotherapy boost dose-escalation for invasive breast cancer after breast-conserving surgery: 2093 Patients treated with a prospective margin-directed policy

Purpose

To investigate the outcome of invasive early breast cancer patients that underwent breast-conserving surgery and adjuvant radiotherapy (RT), treated with a prospective margin-directed institutional policy for RT boost dose, based on final margins status (FMS).

Methods and materials

A total of 2093 patients were treated between 2000 and 2008. 10 Gy boost was prescribed in case of FMS > 5 mm; 16 Gy boost with FMS between 2 and 5 mm; 20 Gy boost in case of FMS < 2 mm or positive.

Results

After a median follow up of 5.2 years, we recorded 41 local relapse (LR, 2%). Concerning LR free survival, age at diagnosis, nuclear grade, hormonal status, T-stage, adjuvant hormonal therapy and adjuvant chemotherapy emerged as significant parameters (p-values from log rank test <0.05). FMS, that directed the RT boost dose, did not have significant impact on LRFS (p = 0.46). LR rates were 2.3% for FMS < 2 mm, 2.6% for 2–5 mm FMS and 1.8% for FMS > 5 mm. At multivariate analysis, higher nuclear grade (p = 0.045), triple negative subtype (p = 0.036) and higher T-stage (p = 0.02) resulted as the independent predictors of LR occurrence.

Conclusions

Our experience showed that a margin-directed policy of RT boost dose-escalation seems to reduce the negative impact of FMS on LR, but it is not able to overcome the unfavorable effect of higher nuclear grade, higher T stage and triple negative subtype.     

Preoperative intensity-modulated and image-guided radiotherapy with a simultaneous integrated boost in locally advanced rectal cancer: Report on late toxicity and outcome

Background and purpose

The addition of chemotherapy to preoperative radiotherapy has been established as the standard of care for patients with cT3-4 rectal cancer. As an alternative strategy, we explored intensity-modulated and image-guided radiotherapy (IMRT–IGRT) with a simultaneous integrated boost (SIB) in a prospective phase II study. Here, we report outcome and late toxicity after a median follow-up of 54 months.

Methods and materials

A total of 108 patients were treated preoperatively with IMRT–IGRT, delivering a dose of 46 Gy in fractions of 2 Gy. Patients (n = 57) displaying an anticipated circumferential resection margin (CRM) of less than 2 mm based on magnetic resonance imaging received a SIB to the tumor up to a total dose of 55.2 Gy.

Results

The absolute incidence of grade ?3 late gastrointestinal and urinary toxicity was 9% and 4%, respectively, with a 13% rate of any grade ?3 late toxicity. The actuarial 5-year local control (LC), progression-free survival (PFS) and overall survival (OS) were 97%, 57%, and 68%. On multivariate analysis, R1 resection and pN2 disease were associated with significantly impaired OS.

Conclusions

The use of preoperative IMRT–IGRT with a SIB resulted in a high 5-year LC rate and non-negligible late toxicity.     

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.     

Hyperfractionated Accelerated Radiotherapy (HART) with maintenance chemotherapy for metastatic (M1–3) Medulloblastoma – A safety/feasibility study

Background and purpose

To evaluate feasibility and toxicity of Hyperfractionated Accelerated Radiotherapy (HART) 1.24 Gy b.i.d. followed by chemotherapy for M1–3 Medulloblastoma (MB). The aim of HART was to use hyperfractionation to improve therapeutic ratio combined with acceleration to minimise tumour cell repopulation during radiotherapy (RT).

Materials and methods

Between February 2002 and May 2008, 34 eligible patients (22 male, 12 female) aged 3–15 years (median 7) with metastatic MB (M1–9; M2–3, M3–22) received HART with a craniospinal radiotherapy (CSRT) dose of 39.68 Gy followed by 22.32 Gy boost to the whole posterior fossa and 9.92 Gy metastatic boosts. The 8th and subsequent patients received vincristine (VCR) 1.5 mg/m² weekly × 8 doses over 8 weeks starting during the 1st week of RT. Maintenance chemotherapy comprised 8 six-weekly cycles of VCR 1.5 mg/m² weekly × 3, CCNU 75 mg/m² and cisplatin 70 mg/m².

Results

Median duration of HART was 34 days (range 31–38). Grade 3–4 toxicities included mucositis (8), nausea (10), anaemia (5), thrombocytopaenia (2), leucopaenia (24). With 4.5-year median follow-up, 3-year EFS and OS were 59% and 71%, respectively. Of 10 relapses, 1 was outside the central nervous system (CNS), 1 posterior fossa alone and 8 leptomeningeal with 3 also associated with posterior fossa.

Conclusion

HART with or without VCR was well tolerated and may have a place in the multi-modality management of high-risk MB.     

Re-irradiation and hyperthermia after surgery for recurrent breast cancer

Purpose

Evaluation of efficacy and side effects of combined re-irradiation and hyperthermia electively or for subclinical disease in the management of locoregional recurrent breast cancer.

Methods and materials

Records of 198 patients with recurrent breast cancer treated with re-irradiation and hyperthermia from 1993 to 2010 were reviewed. Prior treatments included surgery (100%), radiotherapy (100%), chemotherapy (42%), and hormonal therapy (57%). Ninety-one patients were treated for microscopic residual disease following resection or systemic therapy and 107 patients were treated electively for areas at high risk for local recurrences. All patients were re-irradiated to 28–36 Gy (median 32) and treated with 3–8 hyperthermia treatments (mean 4.36). Forty percent of the patients received concurrent hormonal therapy. Patient and tumor characteristics predictive for actuarial local control (LC) and toxicity were studied in univariate and multivariate analysis.

Results

The median follow-up was 42 months. Three and 5 year LC-rates were 83% and 78%. Mean of T90 (tenth percentile of temperature distribution), maximum and average temperatures were 39.8 °C, 43.6 °C, and 41.2 °C, respectively. Mean of the cumulative equivalent minutes (CEM43) at T90 was 4.58 min. Number of previous chemotherapy and surgical procedures were most predictive for LC. Cumulative incidence of grade 3 and 4 late toxicity at 5 years was 11.9%. The number of thermometry sensors and depth of treatment volume were associated with acute hyperthermia toxicity.

Conclusions

The combination of re-irradiation and hyperthermia results in a high LC-rate with acceptable toxicity.     

Whole breast radiotherapy in the lateral decubitus position: A dosimetric and clinical solution to decrease the doses to the organs at risk (OAR)

Purpose

To evaluate whole breast 3D-conformal radiotherapy (RT) delivered in the lateral decubitus position (isocentric lateral decubitus [ILD]) and to report the acute toxicity of a series of consecutive patients treated with ILD.

Materials and methods

From January to December 2010, 56 consecutive patients with large breasts and early-stage breast cancer treated by breast conserving surgery underwent 3D-conformal whole breast RT in the lateral decubitus position. A dose of 50 Gy in 25 fractions via two opposed isocentric beams was prescribed to whole breast, with or without a 16 Gy photon tumor bed boost. Dosimetry of all patients was reviewed, and the acute toxicity of treatment, evaluated weekly using the NCI CTC v3.0 scale, was analyzed.

Results

Median age was 57 years (range: 33–71). 85% of patients had a breast circumference of at least 95 cm and 80% had at least a C cup size. Average breast volume was 991 cm³ (range: 225–2791 cm³). Median dose to the breast was 50 Gy, while median dose to the tumor bed was 16 Gy. Grade 1, 2 and 3 dermatitis developed in 37.5%, 58.9% and 1.8% of patients, respectively. From a dosimetric point of view, doses to the ipsilateral lung were extremely low: average V_1Gy, V_2Gy and V_5Gy were 26.6%, 9.3% and 0.7%, respectively. Average mean lung dose was 0.96 Gy. For the 26 patients with left-sided tumors, heart doses were also extremely low: average V_1Gy, V_2Gy and V_5Gy were 58.8%, 14.2% and 0.7%, respectively. Average mean heart dose was 1.35 Gy.

Conclusion

Whole breast radiotherapy in the lateral decubitus position for patients with large breasts and early-stage breast cancer provides an excellent dosimetric profile, with low doses to the heart and ipsilateral lung. It is also very well tolerated, with a good acute toxicity profile.     

Adjuvant chemoradiotherapy with or without intraoperative radiotherapy for the treatment of resectable locally advanced gastric adenocarcinoma

Purpose

To document the long-term efficacy of intraoperative electron radiotherapy (IOERT) followed by concurrent chemotherapy and external-beam radiotherapy (EBRT) in the management of locally advanced gastric cancer.

Materials and methods

A total of 97 consecutive patients with T3/4 or N+ gastric adenocarcinoma were enrolled. Fifty-one patients received adjuvant chemoradiotherapy (EBRT group) and 46 received IOERT (dose range, 12-15 Gy) followed by chemoradiotherapy (EBRT + IOERT group).

Results

The 5-year locoregional control rates were 50% and 35% in the two groups with or without IOERT, respectively (p = 0.04). Two patients had recurrence within the IOERT field in the EBRT + IOERT group and 14 patients recurred in the same area in the EBRT group (p = 0.02). Multivariate analyses revealed that adjuvant IOERT was an independent prognosticator for both local-regional control (p = 0.02) and disease-free survival (p = 0.05). G3/4 late toxicity was observed in 5 patients in the EBRT + IOERT group, but none in the EBRT group (p = 0.02).

Conclusions

Higher radiation dose may contribute to the improvement of local control, especially in the field encompassed by IOERT. The addition of IOERT to surgery and adjuvant chemoradiation deserves further investigation in a randomized trial.     

Normal tissue complication probability (NTCP) parameters for breast fibrosis: Pooled results from two randomised trials

Introduction

The dose–volume effect of radiation therapy on breast tissue is poorly understood. We estimate NTCP parameters for breast fibrosis after external beam radiotherapy.

Materials and methods

We pooled individual patient data of 5856 patients from 2 trials including whole breast irradiation followed with or without a boost. A two-compartment dose volume histogram model was used with boost volume as the first compartment and the remaining breast volume as second compartment. Results from START-pilot trial (n = 1410) were used to test the predicted models.

Results

26.8% patients in the Cambridge trial (5 years) and 20.7% patients in the EORTC trial (10 years) developed moderate-severe breast fibrosis. The best fit NTCP parameters were BEUD₃(50) = 136.4 Gy, γ50 = 0.9 and n = 0.011 for the Niemierko model and BEUD₃(50) = 132 Gy, m = 0.35 and n = 0.012 for the Lyman Kutcher Burman model. The observed rates of fibrosis in the START-pilot trial agreed well with the predicted rates.

Conclusions

This large multi-centre pooled study suggests that the effect of volume parameter is small and the maximum RT dose is the most important parameter to influence breast fibrosis. A small value of volume parameter ‘n’ does not fit with the hypothesis that breast tissue is a parallel organ. However, this may reflect limitations in our current scoring system of fibrosis.     

Comparison of concomitant boost radiotherapy against concurrent chemoradiation in locally advanced oropharyngeal cancers: A phase III randomised trial

Purpose

To test the toxicity and efficacy of concomitant boost radiotherapy alone against concurrent chemoradiation (conventional fractionation) in locally advanced oropharyngeal cancer in our patient population.

Methods and materials

In this open-label, randomised trial, 216 patients with histologically proven Stage III–IVA oropharyngeal cancer were randomly assigned between June 2006 and December 2010 to receive either chemoradiation (CRT) to a dose of 66 Gy in 33 fractions over 6.5 weeks with concurrent cisplatin (100 mg/m² on days 1, 22 and 43) or accelerated radiotherapy with concomitant boost (CBRT) to a dose of 67.5 Gy in 40 fractions over 5 weeks. The compliance, toxicity and quality of life were investigated. Disease-free survival (DFS) and overall survival (OS) curves were estimated with the Kaplan–Meier method and compared using log rank test.

Results

The compliance to radiotherapy was superior in concomitant boost with lesser treatment interruptions (p = 0.004). Expected acute toxicities were significantly higher in CRT, except for grade 3/4 mucositis which was seen more in CBRT arm (39% and 55% in CRT and CBRT, respectively; p = 0.02). Late toxicities like Grade 3 xerostomia were significantly high in CRT arm than CBRT arm (33% versus 18%; p < 0.0001). The quality of life was significantly poor in CRT arm at all follow up visits (p < 0.0001). The rates of 2 year disease-free survival were similar with 56% in the chemoradiotherapy group and 61% in CBRT group (p = 0.2; HR-0.81, 95%CI-0.53–1.2). Subgroup analysis revealed that patients with nodal size >2 cm had significantly better DFS with CRT (p = 0.05; HR-1.59, 95%CI-0.93–2.7).

Conclusion

In selected patients of locally advanced oropharyngeal cancer, concomitant boost offers a better compliance, toxicity profile and quality of life with similar disease control, than chemoradiation.     

Outcome of a phase II prospective study on partial breast irradiation with interstitial multi-catheter high-dose-rate brachytherapy

Background and purpose

Partial breast irradiation (PBI) is an alternative to whole-breast irradiation after breast-conserving surgery in selected patients. Until the results of randomized phase III studies are available, phase II studies inform about PBI. We report the 5 year results of a phase II prospective study with PBI using interstitial multi-catheter high-dose-rate brachytherapy (ClinicalTrials.gov Identifier: NCT00499057).

Methods

Hundred patients received PBI (4 Gy, twice a day for 4 days, until 32 Gy). Inclusion criteria were: age ?40 years, infiltrating carcinoma without lobular histology, ductal in situ carcinoma, tumor size ?2.5 cm, negative surgical margins and axillary lymph nodes.

Results

At a median follow-up of 60 months late toxicity occurred in 25 patients; the 5-year probability of freedom from late toxicity was 72.6% (95% CI: 63.7–81.7). Tamoxifen was the only significant risk factor for late toxicity. Cosmetic results, judged by physicians and patients, were good/excellent in 98 patients. Three local relapses (1 true, 2 elsewhere) and 1 regional relapse occurred. The 5-year probability of local or regional relapse-free survival was 97.7% (95% CI: 91.1–99.4) and 99.0% (95% CI: 92.9–99.8), respectively.

Conclusion

PBI with interstitial multi-catheter brachytherapy is associated with low relapse and late toxicity rates.     

Local dose–effect relations for lung perfusion post stereotactic body radiotherapy

Purpose

To model the local dose–effect relation for lung perfusion reduction in lung cancer patients treated with stereotactic body radiotherapy (SBRT).

Materials and methods

Forty-two patients having upper-lobe peripheral tumours <5 cm treated with SBRT (3 × 18 Gy) underwent single-photon emission computed-tomography (SPECT) scans to measure the lung perfusion 2 weeks pre-SBRT, 4-months post-SBRT, and for 8 patients 15-months post-SBRT. The relation between the calculated relative local perfusion reduction and the normalised total dose (α/β = 3 Gy) at 4-months post-SBRT was modeled by 3-parameter logistic model and 2-parameter linear-maximum model.

Results

The relation between local dose and perfusion reduction at 4-months post-SBRT showed a maximum effect of 42.6% at doses >100 Gy and was best described by the logistic model with parameters (95% CI): M = 42.6% (40.7–44.6), D₅₀ = 28.7 Gy (26.3–31.1) and k = 2.2 (1.8–2.5). A significant increase of this maximum effect to 65.2% was found at 15-months post-SBRT.

Conclusions

The relation between local dose and perfusion reduction in patients treated with SBRT can be modeled by a 3-parameter logistic model. This demonstrated relationship 4-months post-SBRT approaches a plateau for doses >100 Gy, where 90% of the maximum lung-perfusion reduction is observed at NTD = 78 Gy. A further perfusion reduction compared to 4-months post-SBRT was observed fifteen months post-SBRT.     

The role of radiotherapy in treating small early invasive breast cancer

Aim

The aim of the study was to identify if radiotherapy can be safely avoided in a selected subgroup of largely screening detected small invasive breast cancer.

Methods

One hundred and eighty-eight patients with node negative invasive early breast cancer ≤1 cm (≤T1b) treated in our centre between 1990 and 2004 were retrospectively followed for local, regional and distant recurrences. Treatment involved adequate local excision by breast conserving surgery (BCS). Axillary staging was performed by a four node axillary sampling until 2000, following which sentinel lymph node sampling was employed. All sections were assessed histologically by haematoxylin and eosin stained sections. The inked margins were reported as being involved, close and clear. Radiotherapy (RT) was employed only if the resected margins were inadequate, and in those with involved axillary nodes who refused further completion axillary clearance.

Results

Ninety-four patients (Group A) had BCS alone and 79 patients (Group B) had both BCS and RT. There was no ipsilateral breast tumour recurrence (IBTR) in 88 patients in Group A, corresponding to an actuarial freedom from IBTR of 96%, 91% and 88.1% at 5 years, 8 years and 9 years. In Group B, there was no IBTR in 75 patients corresponding to an actuarial freedom from IBTR of 97%, 94.9% and 90.6% at 5 years, 8 years and 10 years.

Conclusion

Our experience over 14 years has shown that it is possible to safely avoid radiotherapy in a selected subgroup of small invasive breast cancer.     

Risk of second primary lung cancer in women after radiotherapy for breast cancer

Background

Several epidemiological studies have reported increased risks of second lung cancers after breast cancer irradiation. In this study we assessed the effects of the delivered radiation dose to the lung and the risk of second primary lung cancer.

Methods

We conducted a nested case–control study of second lung cancer in a population based cohort of 23,627 early breast cancer patients treated with post-operative radiotherapy from 1982 to 2007. The cohort included 151 cases diagnosed with second primary lung cancer and 443 controls. Individual dose-reconstructions were performed and the delivered dose to the center of the second lung tumor and the comparable location for the controls were estimated, based on the patient specific radiotherapy charts.

Results

The median age at breast cancer diagnosis was 54 years (range 34–74). The median time from breast cancer treatment to second lung cancer diagnosis was 12 years (range 1–26 years). 91% of the cases were categorized as ever smokers vs. 40% among the controls. For patients diagnosed with a second primary lung cancer five or more years after breast cancer treatment the rate of lung cancer increased linearly with 8.5% per Gray (95% confidence interval = 3.1–23.3%; p < 0.001). This rate was enhanced for ever smokers with an excess rate of 17.3% per Gray (95% CI = 4.5–54%; p < 0.005).

Conclusions

Second lung cancer after radiotherapy for early breast cancer is associated with the delivered dose to the lung. Although the absolute risk is relative low, the growing number of long-time survivors after breast cancer treatment highlights the need for advances in normal tissue sparing radiation techniques.     

A prospective randomized trial comparing hypofractionation with conventional fractionation radiotherapy for T1–2 glottic squamous cell carcinomas: Results of a Korean Radiation Oncology Group (KROG-0201) study

Background and purpose

To prospectively investigate the effect of radiotherapy fraction size on clinical outcomes in early glottic carcinoma

Methods and materials

Patients with T1–2 glottic carcinoma were eligible for the protocol. Although 282 patients were required, the study was closed prematurely due to poor accrual with only 156 patients. Of these, 82 patients were allocated to conventional fractionation (CONV) arm (66 Gy/33 fractions for T1 and 70 Gy/35 fractions for T2), with 74 patients to hypofractionation (HYPO) arm (63 Gy/28 fractions for T1 and 67.5 Gy/30 fractions for T2). The primary objective was local progression-free survival (LPFS).

Results

With a median follow-up of 67 months (range, 2–122 months), the 5-year LPFS was 77.8% for CONV arm and 88.5% for HYPO arm (HR 1.55, p = 0.213). No significant difference was observed in the toxicity profile between the two arms. In a subgroup exploratory analysis for T1a disease, the 5-year LPFS trended positively in HYPO arm (76.7% vs. 93.0%, HR 3.65, p = 0.056).

Conclusions

Given that HYPO is at least not inferior to CONV with a similar toxicity profile, the hypofractionation scheme used in this study can be offered to patients with T1–2 glottic carcinoma with potential advantages in terms of local control and a shortened overall treatment time.     

External beam radiotherapy plus single-fraction high dose rate brachytherapy in the treatment of locally advanced prostate cancer

Purpose

To evaluate the efficacy and toxicity of external beam radiation therapy (EBRT) plus high-dose-rate brachytherapy (HDRB) as a boost in patients (pts) with intermediate or high-risk prostate cancer.

Methods and materials

From 2002 to July 2012, 377 pts with a diagnosis of intermediate or high-risk prostate cancer were treated with EBRT plus HDRB. Median patient age was 66 years (range, 41–86). Most patients (347 pts; 92%) were classified as high-risk (stage T2c–T3, or PSA > 20 ng/mL, or GS ? 8), with 30 patients (8%) considered intermediate risk. All patients underwent EBRT at a prescribed dose of 60.0 Gy (range, 45–70 Gy) to the prostate and seminal vesicles. A total of 120 pts (31%) received a dose of 46 Gy (45–50 Gy) to the true pelvis. All pts received a single-fraction 9 Gy (9–15 Gy) HDR boost. Most patients (353; 94%) were prescribed complete androgen deprivation therapy (ADT). Overall survival (OS), cause-specific survival (CSS), and biochemical relapse-free survival (BRFS) rates were calculated. In the case of BRFS, patients with <26 months of follow-up (n = 106) were excluded to minimize the impact of ADT.

Results

The median follow-up for the entire sample was 50 months (range, 12–126), with 5-year actuarial OS and CSS, respectively, of 88% (95% confidence interval [CI]: 84–92) and 98% (95% CI: 97–99). The 5-year BRFS was 91% (95% CI: 87–95) in the 271 pts with ?26 months (median, 60 months) of follow-up. Late toxicity included grade 2 and 3 gastrointestinal toxicity in 17 (4.6%) and 6 pts (1.6%), respectively, as well as grades 2 and 3 genitourinary toxicity in 46 (12.2%) and 3 pts (0.8%), respectively.

Conclusion

These long-term outcomes confirm that EBRT plus a single-fraction HDRB boost provides good results in treatment-related toxicity and biochemical control. In addition to the excellent clinical results, this fractionation schedule reduces physician workload, treatment-related expenses, patient discomfort and risks associated with anaesthesia. We believe these findings support the use of single-fractionation boost techniques.     

Locoregional recurrence in breast carcinoma patients

Aims

To assess the risk of locoregional recurrence (LRR) after mastectomy and to identify predictive and treatment factors that affect the risk of LRR.

Methods

The primary endpoint was local recurrence. Univariate and multivariate Cox regression analyses were carried out in the data from 1217 patients.

Results

The median follow-up was 74 months, and 63 (5.2%) patients experienced a LRR in their follow-up period. In the multivariate analysis, age group (≤35 years vs. >35 years, p < 0.0001; Hazard Ratio [HR], 5.0; 95% Confidence Interval [95% CI], 3.0–8.3), tumour size (>2 cm vs. ≤2 cm, p = 0.03; HR, 2.2; 95% CI, 1.2–4.7) and LVI (yes vs. no, p < 0.0001; HR, 3.2; 95% CI,1.9–5.2) were the independent prognostic factors for LRR. This analysis, in the final model, indicated that adjuvant radiotherapy and adjuvant tamoxifen were associated with a reduced risk of LRR by 90% and 75%, respectively, across the follow-up period, whereas age group remained as an important risk factor (p = 0.002; HR, 3.0; 95% CI, 1.5–6.2).

Conclusions

Although adjuvant therapies reduce the risk of LRR, young age is an independent risk factor for LRR.     

Retrograde superselective intra-arterial chemotherapy and daily concurrent radiotherapy for stage III and IV oral cancer: Analysis of therapeutic results in 112 cases

Purpose

To evaluate the therapeutic results and rate of organ preservation in patients with stage III or IV oral cancer treated with retrograde superselective intra-arterial chemotherapy and daily concurrent radiotherapy.

Materials and methods

One hundred and twelve patients with stage III and IV oral squamous cell carcinoma underwent intra-arterial chemoradiotherapy. Catheterization from the superficial temporal and occipital arteries was performed. Treatment consisted of superselective intra-arterial chemotherapy (docetaxel, total 60 mg/m², cisplatin, total 150 mg/m²) and daily concurrent radiotherapy (total of 60 Gy) for 6 weeks.

Results

The median follow-up for all patients was 46.2 months (range, 10–76 months). After intra-arterial chemoradiotherapy, primary site complete response was achieved in 98 (87.5%) of 112 cases. Five-year survival and local control rates were 71.3% and 79.3%, respectively. Grade 3 or 4 toxicities included mucositis in 92.0%, neutropenia in 30.4%, dermatitis in 28.6%, anemia in 26.8%, and thrombocytopenia in 7.1% of patients. Grade 3 toxicities included dysphagia in 72.3%, nausea/vomiting in 21.4%, fever in 8.0%, and renal failure in 0.9% of patients.

Conclusion

Retrograde superselective intra-arterial chemotherapy and daily concurrent radiotherapy for stage III and IV oral cancer provided good overall survival and local control.     

Applicability of the linear-quadratic formalism for modeling local tumor control probability in high dose per fraction stereotactic body radiotherapy for early stage non-small cell lung cancer

Background and purpose

To compare the linear-quadratic (LQ) and the LQ-L formalism (linear cell survival curve beyond a threshold dose d_T) for modeling local tumor control probability (TCP) in stereotactic body radiotherapy (SBRT) for stage I non-small cell lung cancer (NSCLC).

Materials and methods

This study is based on 395 patients from 13 German and Austrian centers treated with SBRT for stage I NSCLC. The median number of SBRT fractions was 3 (range 1–8) and median single fraction dose was 12.5 Gy (2.9–33 Gy); dose was prescribed to the median 65% PTV encompassing isodose (60–100%). Assuming an α/β-value of 10 Gy, we modeled TCP as a sigmoid-shaped function of the biologically effective dose (BED). Models were compared using maximum likelihood ratio tests as well as Bayes factors (BFs).

Results

There was strong evidence for a dose–response relationship in the total patient cohort (BFs > 20), which was lacking in single-fraction SBRT (BFs < 3). Using the PTV encompassing dose or maximum (isocentric) dose, our data indicated a LQ-L transition dose (d_T) at 11 Gy (68% CI 8–14 Gy) or 22 Gy (14–42 Gy), respectively. However, the fit of the LQ-L models was not significantly better than a fit without the d_T parameter (p = 0.07, BF = 2.1 and p = 0.86, BF = 0.8, respectively). Generally, isocentric doses resulted in much better dose–response relationships than PTV encompassing doses (BFs > 20).

Conclusion

Our data suggest accurate modeling of local tumor control in fractionated SBRT for stage I NSCLC with the traditional LQ formalism.     

Additional weekly Cetuximab to concurrent chemoradiotherapy in locally advanced non-small cell lung carcinoma: Efficacy and safety outcomes of a randomized,multi-center phase II study investigating

Background

Modest benefits from concurrent chemoradiotherapy in patients with locally advanced NSCLC warrant further clinical investigations to identify more effective treatment regimens. Cetuximab, a monoclonal antibody against the epidermal growth factor receptor has shown activity in NSCLC. We report on the safety and efficacy of the combination of daily dose Cisplatin and concurrent radiotherapy with or without weekly Cetuximab.

Patients and methods

Patients received high dose accelerated radiotherapy (66 Gy in 24 fractions) and concurrent daily Cisplatin (6 mg/m²) without (Arm A) or with (Arm B) weekly Cetuximab (400 mg/m² loading dose one week prior to radiotherapy followed by weekly 250 mg/m²). The primary endpoint of the trial was objective local control rate (OLCR) determined at 6–8 weeks after treatment. Toxicity was reported as well.

Results

Between February 2009 and May 2011, 102 patients were randomized. Median follow up was 29 months. The OLCR was 84% in Arm A and 92% in Arm B (p = 0.36). The one-year local progression free interval (LPFI) and overall survival (OS) were 69% and 82% for Arm A and 73% and 71% for Arm B, respectively (LPFI p = 0.39; OS p = 0.99). Toxicity compared equally between both groups.

Conclusion

The addition of Cetuximab to radiotherapy and concurrent Cisplatin did not improve disease control in patients with locally advanced NSCLC but increased treatment related toxicity.