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.     

Preoperative chemoradiation in adenocarcinoma of the pancreas. A single centre experience advocating a new treatment strategy

Aims

To evaluate a single centre's experience with pancreatic carcinoma focused on preoperative chemoradiation therapy (CRT) for treatment of locally advanced pancreatic carcinoma. The aim of the present analysis was to evaluate the median overall survival time (OS) after preoperative CRT and to compare it with OS after primary resection of pancreatic carcinoma. In conclusion a new treatment strategy was developed using multimodality treatment for pancreatic carcinoma deemed to be resectable by CT-scan.

Patients and methods

Between 1995 and 2003, 302 patients with ductal adenocarcinoma of the pancreatic head and body were recorded prospectively and OS was analysed with regard to therapy.

Results

Fifty-eight patients were resected without any pretreatment and had an OS of 21 months. Twenty-one patients with initially unresectable tumours underwent CRT followed by resection and had an OS of 54 months, which was not significantly different from primary resection (p = 0.315). Lymph node metastasis was significantly reduced after CRT (p = 0.0029). OS for patients whose tumours could not be resected was 3–10 months, depending on tumour stage and consecutive therapy.

Conclusion

CRT pretreatment was effective in locally advanced pancreatic carcinoma and resulted in resection of tumours otherwise staged as non-resectable. This experience led to a randomized trial for patients who by CT are staged to have resectable cancer of the pancreatic head with the intent to increase curative resectability and survival by neoadjuvant CRT (ISRCTN78805636/NCT00335543).     

Lymph node ratio is an independent prognostic factor in patients with rectal cancer treated with preoperative chemoradiotherapy and curative resection

Purpose

To evaluate the prognostic effect of lymph node ratio (LNR) in patients with locally advanced rectal cancer who were treated with curative resection after preoperative chemoradiotherapy (CRT).

Methods

Between October 2001 and December 2007, 519 patients who had undergone curative resection of primary rectal cancer after preoperative CRT were enrolled. Of these, 154 patients were positive for lymph node (LN) metastasis and were divided into three groups according to the LNR (≤0.15 [n = 80], 0.16–0.3 [n = 44], >0.3 [n = 30]) to evaluate the prognostic effect on overall survival (OS) and disease-free survival (DFS).

Results

LNR (≤0.15, 0.16–0.3, and >0.3) was significantly associated with 5-year OS (90.3%, 75.1%, and 45.1%; p < 0.001) and DFS (66.7%, 55.8%, and 21.9%; p < 0.001) rates. In a multivariate analysis, LNR (≤0.15, 0.16–0.3, and >0.3) was a significant independent prognostic factor for OS (hazard ratios [HRs], 1, 3.609, and 8.197; p < 0.001) and DFS (HRs, 1, 1.699, and 3.960; p < 0.001). LNR had a prognostic impact on OS and DFS in patients with <12 harvested LNs, as well as in those with ≥12 harvested LNs (p < 0.05).

Conclusion

LNR was a significant independent prognostic predictor for OS and DFS in patients with locally advanced rectal cancer who were treated with curative resection after preoperative CRT.     

Efficacy and safety of maintenance pemetrexed in patients with advanced nonsquamous non-small cell lung cancer following pemetrexed plus cisplatin induction treatment: A cross-trial comparison of two phase III trials

Objectives

Two phase III trials of advanced NSCLC patients were compared to examine relative efficacy and safety of differing treatment regimens. The JMDB trial investigated first-line pemetrexed–cisplatin (pemetrexed 500 mg/m² plus cisplatin 75 mg/m² every 21 days; maximum: 6 cycles). The PARAMOUNT phase III trial compared maintenance pemetrexed versus placebo after patients with nonsquamous NSCLC completed 4 cycles of first-line pemetrexed–cisplatin without disease progression.

Methods

Overall survival (OS) and progression-free survival (PFS), analyzed by Kaplan–Meier and Cox methods, and toxicity rates were compared between the PARAMOUNT arms and a selected homogeneous population from JMDB: 346 patients with disease and prior treatment characteristics matching the PARAMOUNT population.

Results

Outcomes for the PARAMOUNT placebo arm were similar to the JMDB homogeneous group (median PFS: 5.6 versus 6.2 months, p = 0.117, HR = 1.16; median OS: 14.0 versus 14.2 months, p = 0.979, HR = 1.00). The PARAMOUNT maintenance pemetrexed group had statistically superior efficacy compared with the JMDB homogeneous group (median PFS: 7.5 versus 6.2 months, p < 0.00001, HR = 0.66; median OS: 16.9 versus 14.2 months, p = 0.003, HR = 0.75). Patients who received pemetrexed maintenance (median 4 cycles, range 1–44) following 4 cycles of pemetrexed–cisplatin exhibited a higher incidence of drug-related serious adverse events compared with JMDB patients (median 6 cycles of pemetrexed–cisplatin) (10.6% versus 2.9%); grade 3/4 fatigue and renal toxicity were also higher in the pemetrexed arm of PARAMOUNT.

Conclusions

The across-trial comparison of a relevant JMDB study population with the two arms of the PARAMOUNT study supported the efficacy of the pemetrexed continuation maintenance strategy and suggested the results are not influenced by limiting the pemetrexed–cisplatin induction treatment to four cycles. Although longer exposure to pemetrexed–cisplatin or maintenance pemetrexed increased some toxicities, the overall incidence remained low, underscoring the relative safety of these treatment regimens.     

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.     

Predictors of PEG dependence after IMRT ± chemotherapy for oropharyngeal cancer

Purpose

To prospectively assess predictors of PEG dependence after IMRT with/without concomitant chemotherapy (CHT).

Methods and materials

One-hundred-seventy-one patients were considered (exclusive RT: 58, RT+CHT: 113; 159/171 treated at a median dose of 70 Gy, 2 Gy/fr). Patients treated with RT+CHT underwent prophylactic PEG insertion; PEG was as needed for the others. A number of clinical factors and dose–volume information concerning oral mucosa (OM), constrictors, masticatory muscles, larynx, esophagus and parotids were available. The 25th/10th percentiles of the duration of PEG dependence were our end-points (respectively 3.3 and 7 months, PEG3/PEG7). Logistic uni and multi-variate (MVA) analyses were performed.

Results

Concerning PEG3, the independent predictors at MVA were: CHT/PEG policy (OR: 6.8, p = 0.001), V9.5G_OM Gy/week (OR: 1.017, p = 0.01), larynx V50 (OR: 1.018, p = 0.01) and superior constrictor (SC) D_mean (OR: 1.002, p = 0.005); the predictive value of the model (AUC) was 0.818 (95% CI: 0.751–0.873). The independent predictors of PEG7 were: larynx V50 (OR: 1.042, p = 0.0005) and SC D_mean (OR: 1.003, p = 0.02), symptoms at diagnosis (yes vs no, OR: 3.6, p = 0.08) and sex (male vs female, OR: 0.25, p = 0.07); AUC was 0.897 (95% CI: 0.841–0.939).

Conclusions

OM V9.5 Gy/week and CHT/PEG_policy modulate the risk of early PEG dependence. For longer PEG dependence, larynx V50 (or D_mean) and SC D_mean are highly predictive, suggesting that the fibrosis of constrictors and larynx is the main cause.     

Results of single-probe microwave ablation of metastatic liver cancer

Aims

Microwave ablation (MWA) is the most recent development in the field of local ablative therapies. The aim of this study was to evaluate the variability and reproducibility of single-probe MWA vs. radiofrequency ablation (RFA) of liver metastases smaller than 3 cm in patients without underlying liver disease.

Methods

Sixteen liver metastases were treated using MWA, and matched for size and localisation with 13 metastases treated by RFA. Tumour diameters and postoperative ablation diameters were recorded (D1 transverse; D2 antero-posterior; D3 cranio-caudal; mm) on computed tomography scans.

Results

Median D1, D2, and D3 ablation diameters after MWA vs. RFA were 18.5 (12–64) vs. 34 (16–41) mm (p = 0.003), 26 (14–60) vs. 35 (28–40) mm (p = 0.046), and 20 (10–73) vs. 32 (20–45) mm (p = 0.025), respectively. As compared to RFA, the variability between the lesions after MWA was significantly higher for D2 (p < 0.0001) and D3 (p = 0.002) but not for D1 (p = 0.15). The ablation diameters were less uniform after MWA than after RFA (p < 0.001).

Conclusion

Ablation diameters after single-probe MWA of metastatic liver tumours are highly variable and suboptimal. Improvements are needed before MWA can be implemented routinely.     

Atherosclerotic lesions in lymphoma survivors treated with radiotherapy

Background and purpose

Radiotherapy causes premature atherosclerosis in Hodgkin’s lymphoma survivors (HLSs). We determined whether atherosclerosis within the radiation field was predicted by traditional risk factors independent of radiation and compared the extent of atherosclerosis in HLSs treated with mantle field radiotherapy with non-irradiated patients.

Material and methods

Forty-three HLSs (median age 50 years, range 38–63) treated with mantle field radiotherapy were included. Cardiovascular risk factors were registered at first follow-up (FU-1) 5–13 years after treatment. A second follow-up (FU-2) occurred 18–27 years after treatment. At FU-2, in-field atherosclerosis was assessed by computed tomography with calculation of coronary artery calcium volume score (CACS) and pre-cranial artery atherosclerosis score (PAS). Peripheral endothelial dysfunction was assessed by ante-brachial strain-gauge plethysmography. CT angiography of pre-cranial vessels was also performed in 43 non-irradiated patients.

Results

Multiple linear regression analyses showed that cholesterol at FU-1 was a predictor of CACS (β 308 (95% CI 213–403), p < 0.001), PAS (β 3.67 (95% CI 2.29–5.04), p < 0.001) and peripheral endothelial dysfunction (β 2.74 (95% CI 0.47–5.01), p = 0.02). There were more atherosclerotic lesions in HLSs (n = 141) than in non-irradiated patients (n = 73, p = 0.001).

Conclusion

Irradiated arteries are characterized by widespread atherosclerotic lesions aggravated by elevated levels of cholesterol.     

Blood biomarkers are helpful in the prediction of response to chemoradiation in rectal cancer: A prospective,hypothesis driven study on patients with locally advanced rectal cancer

Purpose/objective

Chemoradiation (CRT) has been shown to lead to downsizing of an important portion of rectal cancers. In order to tailor treatment at an earlier stage during treatment, predictive models are being developed. Adding blood biomarkers may be attractive for prediction, as they can be collected very easily and determined with excellent reproducibility in clinical practice. The hypothesis of this study was that blood biomarkers related to tumor load, hypoxia and inflammation can help to predict response to CRT in rectal cancer.

Material/methods

295 patients with locally advanced rectal cancer who were planned to undergo CRT were prospectively entered into a biobank protocol (NCT01067872). Blood samples were drawn before start of CRT. Nine biomarkers were selected, based on a previously defined hypothesis, and measured in a standardized way by a certified lab: CEA, CA19-9, LDH, CRP, IL-6, IL-8, CA IX, osteopontin and 25-OH-vitamin D. Outcome was analyzed in two ways: pCR vs. non-pCR and responders (defined as ypT0-2N0) vs. non-responders (all other ypTN stages).

Results

276 patients could be analyzed. 20.7% developed a pCR and 47.1% were classified as responders. In univariate analysis CEA (p = 0.001) and osteopontin (p = 0.012) were significant predictors for pCR. Taking response as outcome CEA (p < 0.001), IL-8 (p < 0.001) and osteopontin (p = 0.004) were significant predictors. In multivariate analysis CEA was the strongest predictor for pCR (OR 0.92, p = 0.019) and CEA and IL-8 predicted for response (OR 0.97, p = 0.029 and OR 0.94, p = 0.036). The model based on biomarkers only had an AUC of 0.65 for pCR and 0.68 for response; the strongest model included clinical data, PET-data and biomarkers and had an AUC of 0.81 for pCR and 0.78 for response.

Conclusion

CEA and IL-8 were identified as predictive biomarkers for tumor response and PCR after CRT in rectal cancer. Incorporation of these blood biomarkers leads to an additional accuracy of earlier developed prediction models using clinical variables and PET-information. The new model could help to an early adaptation of treatment in rectal cancer patients.     

Evaluation and impact of residual disease in locally advanced cervical cancer after concurrent chemoradiation therapy: Results of a multicenter study

Background

The aim of this study was to evaluate the diagnosis and impact of residual disease (RD) after concurrent chemoradiation therapy (CRT) in locally advanced cervical cancer (FIGO IB2-IVA).

Methods

This retrospective multicenter study included 159 patients who were treated with completion surgery after CRT between 2006 and 2012. Magnetic resonance imaging (MRI) was performed 4–6 weeks after CRT and compared to pathological evidence of residual disease. Kaplan–Meier survival curves were plotted and univariate/multivariate analyses were performed to assess the association between RD and the outcome.

Results

Residual disease was present in 45.3% of the patients and detected by MRI in 57.1%. The MRI had a 29.2% false positive rate and an 11.1% false negative rate. The overall survival (OS) rates at 3 and 5 years were 78.6% (CI 95% [71%–86.9%]) and 76.5% (CI 95% [68.2%–85.7%]), respectively. The disease free survival (DFS) rates at 3 and 5 years were 73.4% (CI 95% [65.6%–82%]) and 71.1% (CI 95% [62.7%–80.1%]), respectively. RD greater than 10 mm decreased DFS (HR = 4.84, p = 0.03), whereas RD between 1 and 10 mm (HR = 0.31, p = 0.58) and less than 1 mm (HR = 0.37, p = 0.54) had no impact on DFS. The OS was not changed by RD.

Discussion

The MRI accuracy value is not sufficient to select patients who might benefit from completion surgery. Residual disease over 10 mm decreased DFS but did not impact OS.     

Population-based outcomes of boost versus salvage radiosurgery for brain metastases after whole brain radiotherapy

Purpose

We conducted a retrospective population-based study to examine the survival outcomes in patients with brain metastases treated with salvage stereotactic radiosurgery (SRS), compared to boost SRS, after previous whole brain radiotherapy (WBRT).

Methods and materials

From January 2000 to June 2011, 191 patients treated with WBRT and SRS for brain metastases in British Columbia were studied. Patients were divided into a boost cohort and a salvage cohort. The criteria used to determine eligibility for SRS were: 1–3 metastases, ?4 cm size, Karnofsky performance status ?70, and control of extracranial disease.

Results

Diagnosis by primary site was 84 lung, 47 breast, 15 melanoma, 12 renal, 9 colorectal, and 24 other. There were 113 patients (59%) in the boost cohort and 78 patients (41%) in the salvage cohort. The median overall survival from WBRT for the whole population was 17.7 months: 12.1 months for the boost cohort and 22.7 months for the salvage cohort. There was no difference in median survival after SRS for the boost and salvage cohorts (11.2 vs. 11.2 months, p = 0.78).

Conclusions

In selected patients with brain metastases treated with WBRT, survival following salvage SRS is as good as survival after WBRT + boost SRS.     

Equivalent survival in patients with advanced stage IB–II and III–IVA cervical cancer treated by adjuvant surgery following chemoradiotherapy

Objectives

To evaluate survival in patients with advanced cervical cancer who underwent surgery after concurrent chemoradiotherapy.

Methods

One hundred and forty-four patients with biopsy-proven stage IB–IVA cervical cancer underwent adjuvant surgery after concurrent chemoradiotherapy. Surgical resection was classified as curative (no evidence of remaining disease after surgery) or palliative (remaining disease after surgery). Endpoints were pelvic control, overall survival (OS) and disease-free survival (DFS) at 5 and 10 years. Analysis included tumour FIGO stage, type of surgery (curative versus palliative), pelvic control, response to chemoradiotherapy and lymphatic status.

Results

Tumour FIGO stages were IB–II in 91 cases and III–IVA in 53 cases. Surgery was curative in 127 cases. Pelvic control was achieved in 114 patients and was equivalent in stage IB–II and III–IVA patients. So far, 60 patients have died. The 5-year OS and DFS rates were, respectively, 57.6% [95% CI: 49.1–67.5] and 65% [95% CI: 56.2–75]. OS was significantly affected by the type of surgery (p < 2.10⁻¹⁶), the presence of tumoural residue (p = 0.002) and the pelvic lymphatic status (p < 0.001). DFS was affected by the pelvic (p = 0.02) and para-aortic lymphatic status (p = 0.009). No significant difference was observed between OS and DFS in stage IB–II and III–IVA patients, whereas a macroscopic tumoural residue was observed in, respectively, 30.9 and 52.2% of cases (p = 0.022).

Conclusion

Survival rates were equivalent between patients with IB–II and III–IVA cervical cancer, suggesting that adjuvant surgery following chemoradiotherapy may improve local control.     

Is concurrent radiation therapy required in patients receiving preoperative chemotherapy for adenocarcinoma of the oesophagus? A randomised phase II trial

Introduction

Preoperative chemotherapy (CT) and preoperative chemoradiation therapy (CRT) for resectable oesophageal cancer have been shown to improve overall survival in meta-analyses. There are limited data comparing these preoperative therapies. We report the outcomes of a randomised phase II trial comparing preoperative CT and CRT for resectable adenocarcinoma of the oesophagus and gastro-oesophageal junction.

Methods

Patients were randomised to receive preoperative CT with cisplatin (80 mg/m²) and infusional 5 fluorouracil (1000 mg/m²/d) on days 1 and 21, or preoperative CRT with the same drugs accompanied by concurrent radiation therapy commencing on day 21 of chemotherapy and the 5 fluorouracil reduced to 800 mg/m²/d. The radiation dose was 35 Gy in 15 fractions over 3 weeks. The endpoints were toxicity, response rates, resection (R) status, progression-free survival (PFS), overall survival (OS) and quality of life.

Results

Seventy-five patients were enroled on the study: 36 received preoperative CT and 39 preoperative CRT. Toxicity was similar for CT and CRT. Eight patients (11%) did not proceed to resection. The histopathological response rate (CRT 31% versus CT 8%, p = 0.01) and R1 resection rate (CRT 0% versus CT 11%, p = 0.04) favoured those receiving CRT. The median PFS was 14 and 26 months for CT and CRT respectively (p = 0.37). The median OS was 29 months for CT compared with 32 months for CRT (p = 0.83).

Conclusions

Despite no difference in survival, the improvement from preoperative CRT with respect to margin involvement makes this treatment a reasonable option for bulky, locally advanced resectable adenocarcinoma of the oesophagus.     

IORT with electrons as boost strategy during breast conserving therapy in limited stage breast cancer: Long term results of an ISIORT pooled analysis

Purpose

Linac-based intraoperative radiotherapy with electrons (IOERT) was implemented to prevent local recurrences after breast conserving therapy (BCT) and was delivered as an intraoperative boost to the tumor bed prior to whole breast radiotherapy (WBI). A collaborative analysis has been performed by European ISIORT member institutions for long term evaluation of this strategy.

Material and methods

Until 10/2005, 1109 unselected patients of any risk group have been identified among seven centers using identical methods, sequencing and dosage for intra- and postoperative radiotherapy. A median IOERT dose of 10 Gy was applied (90% reference isodose), preceding WBI with 50–54 Gy (single doses 1.7–2 Gy).

Results

At a median follow up of 72.4 months (0.8–239), only 16 in-breast recurrences were observed, yielding a local tumor control rate of 99.2%. Relapses occurred 12.5–151 months after primary treatment. In multivariate analysis only grade 3 reached significance (p = 0.031) to be predictive for local recurrence development. Taking into account patient age, annual in-breast recurrence rates amounted 0.64%, 0.34%, 0.21% and 0.16% in patients <40 years; 40–49 years; 50–59 years and ?60 years, respectively.

Conclusion

In all risk subgroups, a 10 Gy IOERT boost prior to WBI provided outstanding local control rates, comparing favourably to all trials with similar length of follow up.     

A phase II trial evaluating the clinical and immunologic response of HLA-A2 non-small cell lung cancer patients vaccinated with an hTERT cryptic peptide

Objectives

The immunological and clinical responses of patients with NSCLC treated, in the context of an expanded action program, with the cryptic hTERT-targeting Vx-001 vaccine are presented.

Materials and methods

Forty-six HLA-A*0201-positive patients with advanced NSCLC and residual (n = 27) or progressive (n = 19) disease following front-line treatment received two subcutaneous injections of the optimized TERT_572Y peptide followed by four injections of the native TERT₅₇₂ peptide, every 3 weeks. Peptide-specific immune responses were monitored by enzyme-linked immunosorbent spot assay at baseline, and after the 2nd and the 6th vaccinations. Thirty-eight HLA-A*0201-positive matched patients were used as historical controls.

Results

Twenty-three patients (50%) completed the vaccination protocol and 87% received at least two administrations. Twelve patients (26%) without disease progression after the 6th vaccination received boost vaccinations. Three (7%) patients achieved a partial response and 13 (28%) disease stabilization. The disease control rate was significantly higher in patients with non-squamous histology compared to those with squamous-cell histology [n = 14 (45%) versus n = 2 (13%); p = 0.03]. The median progression-free survival (PFS) and overall survival (OS) was 3.8 (range, 0.7–99.4) and 19.8 months (range, 0.7–99.4), respectively. Patients who developed immune response had a numerically higher PFS compared to those who failed to mount any (6.7 versus 2.7 months; p = 0.090). However, the median OS for the immune-responders was significantly prolonged compared to non-responders (40.0 versus 9.2 months, respectively; p = 0.02). Toxicity was <grade 2.

Conclusion

Vx-001 vaccine is well tolerated and induced a TERT-specific immunological response, which was significantly correlated with improved clinical outcome.     

Prediction of response to radiotherapy in the treatment of esophageal cancer using stem cell markers

Background and purpose

In this study, we investigated whether cancer stem cell marker expressing cells can be identified that predict for the response of esophageal cancer (EC) to CRT.

Materials and methods

EC cell-lines OE-33 and OE-21 were used to assess in vitro, stem cell activity, proliferative capacity and radiation response. Xenograft tumors were generated using NOD/SCID mice to assess in vivo proliferative capacity and tumor hypoxia. Archival and fresh EC biopsy tissue was used to confirm our in vitro and in vivo results.

Results

We showed that the CD44+/CD24− subpopulation of EC cells exerts a higher proliferation rate and sphere forming potential and is more radioresistant in vitro, when compared to unselected or CD44+/CD24+ cells. Moreover, CD44+/CD24− cells formed xenograft tumors faster and were often located in hypoxic tumor areas.In a study of archival pre-neoadjuvant CRT biopsy material from EC adenocarcinoma patients (N = 27), this population could only be identified in 50% (9/18) of reduced-responders to neoadjuvant CRT, but never (0/9) in the complete responders (P = 0.009).

Conclusion

These results warrant further investigation into the possible clinical benefit of CD44+/CD24− as a predictive marker in EC patients for the response to chemoradiation.     

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.     

Trimodality therapy for stage IIIA non-small cell lung cancer: Benchmarking multi-disciplinary team decision-making and function

Objectives

Although the standard treatment for patients with stage IIIA non-small cell lung cancer (NSCLC) is chemoradiotherapy, some patients are considered for trimodality therapy [TT]. We analyzed outcomes for stage IIIA NSCLC, treated with TT and compared them with concurrent chemoradiotherapy [con-CRT].

Materials and methods

Patients treated between January 2007 and December 2011 were retrospectively analyzed. Not included were patients with sulcus superior tumors, unknown T/N-status, or recurrent disease after con-CRT followed by surgery. All patients were discussed at our multidisciplinary thoracic tumor board (MTB).

Results

Mean Charlson Comorbidity Index was 2 for TT and con-CRT patients. TT patients were younger (median TT = 56 years vs. con-CRT = 62 years; p = 0.001) and had less advanced cN-stage (TT cN2 = 41% vs. 83% for CRT; p < 0.001). 44% of TT patients had T4-stage vs. 12% of con-CRT patients. Median RT dose was lower for TT (50 Gy vs. 66 Gy; p = 0.001) and median RT planning target volume (PTV) in TT and con-CRT patients was 525 cm³ and 655 cm³ (p = 0.010), respectively. The majority of TT patients had a lobectomy (23/32). Median follow-up was 30.3 months (95% CI = 18.7–41.9) for TT and 51 months (95% CI = 24.9–77.4) for con-CRT. Median overall survival was not reached for TT and was 18.6 months (95% CI = 12.8–24.4) for con-CRT (p = 0.001). For PTV </≥ 500 cm³, median OS for TT was not reached/33.9 months and 29.1/17.1 months for con-CRT. TT patients with cN0/1 had better survival than those receiving con-CRT (p = 0.015), but those with cN2 did not (p = 0.158). The 90-day mortality from start of RT was 0% (0/32) for TT and 1.7% (1/58) for con-CRT. 90-day post-operative mortality for TT was 3.1% (1/32, event unrelated to TT).

Conclusions

Selected patients with IIIA NSCLC treated with TT had favorable long-term survival with acceptable short-term mortality. These outcomes support the decision-making and function of our MTB/treatment team. The role of TT in cN2 disease and large tumors merits further evaluation.     

Hypofractionated conformal radiotherapy for pediatric diffuse intrinsic pontine glioma (DIPG): A randomized controlled trial

Background

The pediatric diffuse intrinsic pontine glioma (DIPG) outcome remains dismal despite multiple therapeutic attempts.

Purpose

To compare the results of treatment of pediatric diffuse intrinsic pontine glioma (DIPG) using hypofractionated versus conventional radiotherapy.

Patients and methods

Seventy-one newly diagnosed DIPG children were randomized into hypofractionated (HF) (39 Gy/13 fractions in 2.6 weeks) and conventional (CF) arm (54 Gy/30 fractions in 6 weeks).

Results

The median and one-year overall survival (OS) was 7.8 months and 36.4 ± 8.2% for the hypofractionated arm, and 9.5 and 26.2 ± 7.4% for the conventional arm respectively. The 18-month OS difference was 2.2%. The OS hazard ratio (HR) was 1.14 (95% CI: 0.70–1.89) (p = 0.59).The hypofractionated arm had a median and one-year progression-free survival (PFS) of 6.6 months and 22.5 ± 7.1%, compared to 7.3 and 17.9 ± 7.1% for the conventional arm. The PFS HR was 1.10 (95% CI: 0.67–1.90) (p = 0.71). The 18-month PFS difference was 1.1%. These differences exceed the non-inferiority margin.The immediate and delayed side effects were not different in the 2 arms.

Conclusions

Hypofractionated radiotherapy offers lesser burden on the patients, their families and the treating departments, with nearly comparable results to conventional fractionation, though not fulfilling the non-inferiority assumption.     

Recombinant human thyrotropin-aided versus thyroid hormone withdrawal-aided radioiodine treatment for differentiated thyroid cancer after total thyroidectomy: A meta-analysis

Background and purpose

We conducted a meta-analysis of randomized controlled trials (RCTs) to compare the effects of recombinant human thyrotropin (rhTSH) and thyroid hormone withdrawal (THW) on thyrotropin stimulation prior to remnant ablation of differentiated thyroid cancer (DTC).

Material and methods

A comprehensive search was conducted for articles discussing rhTSH and THW prior to December 2012. After applying the inclusion criteria, all the available data were summarized to analyze the efficacy of rhTSH and THW for stimulating TSH.

Results

Seven RCTs that involved a total of 1535 patients, were included in the analysis. The ablation rates of the rhTSH group and the THW group were not significantly different (RR = 0.97, 95% CI: 0.94–1.01, p = 0.1). Patients in the rhTSH group had a better quality of life (QoL) than those in the THW group on the day of ablation (RR = 3.92, 95% CI: 3.44–5.40, p < 0.00001). However, there was no difference in the QoL 3 months after ablation (RR = −0.9, 95% CI: −2.20–0.39, p = 0.17). Additionally, there were no significant differences in serum thyroglobulin (Tg) levels measured just before radioiodine remnant ablation (preablation thyroglobulin levels) (RR = −0.14, 95% CI: −0.73–0.45, p = 0.65), or in days of hospital isolation (RR = −10.51, 95% CI: −32.79–11.73, p = 0.35)

Conclusions

Our findings indicate that the administration of rhTSH had resulted in an ablation rate similar to that of THW for DTC patients, but rhTSH provided a better QoL at the time of ablation.