Elective nodal irradiation (ENI) vs. involved field radiotherapy (IFRT) for locally advanced non-small cell lung cancer (NSCLC): A comparative analysis of toxicities and clinical outcomes

Background

Elective nodal irradiation (ENI) and involved field radiotherapy (IFRT) are definitive radiotherapeutic approaches used to treat patients with locally advanced non-small cell lung cancer (NSCLC). ENI delivers prophylactic radiation to clinically uninvolved lymph nodes, while IFRT only targets identifiable gross nodal disease. Because clinically uninvolved nodal stations may harbor microscopic disease, IFRT raises concerns for increased nodal failures. This retrospective cohort analysis evaluates failure rates and treatment-related toxicities in patients treated at a single institution with ENI and IFRT.

Methods

We assessed all patients with stage III locally advanced or stage IV oligometastatic NSCLC treated with definitive radiotherapy from 2003 to 2008. Each physician consistently treated with either ENI or IFRT, based on their treatment philosophy.

Results

Of the 108 consecutive patients assessed (60 ENI vs. 48 IFRT), 10 patients had stage IV disease and 95 patients received chemotherapy. The median follow-up time for survivors was 18.9 months. On multivariable logistic regression analysis, patients treated with IFRT demonstrated a significantly lower risk of high grade esophagitis (Odds ratio: 0.31, p = 0.036). The differences in 2-year local control (39.2% vs. 59.6%), elective nodal control (84.3% vs. 84.3%), distant control (47.7% vs. 52.7%) and overall survival (40.1% vs. 43.7%) rates were not statistically significant between ENI vs. IFRT.

Conclusions

Nodal failure rates in clinically uninvolved nodal stations were not increased with IFRT when compared to ENI. IFRT also resulted in significantly decreased esophageal toxicity, suggesting that IFRT may allow for integration of concurrent systemic chemotherapy in a greater proportion of patients.     

Tubulin, BRCA1, ERCC1, Abraxas, RAP80 mRNA expression, p53/p21 immunohistochemistry and clinical outcome in patients with advanced non small-cell lung cancer receiving first-line platinum-gemcitabine chemotherapy

Background

The aim of this study was to assess the predictive value of tumor expression of nine genes on clinical outcome in patients with advanced NSCLC receiving platinum-gemcitabine chemotherapy.

Methods

Quantitative PCR or immunohistochemistry were used to analyze the expression of β-tubuline IIA (TUBB2A), β-tubuline III (TUBB3), BRCA1, ERCC1, Abraxas (ABRX) and RAP80 in mRNA isolated from paraffin-embedded tumor biopsies of 45 NSCLC patients treated as part of a larger observational trial. All patients received first-line platinum-gemcitabine chemotherapy for stage IIIB or IV NSCLC.

Results

Median progression-free survival (PFS) was 7 months, overall survival (OS) 12 months. A partial treatment response was found in 14 patients (33%). Patients with low ERCC1 or ABRX expression had a significantly better response to chemotherapy (R = −0.45, p < 0.01 for ERCC1; R = −0.40, p = 0.016 for ABRX). A significant correlation was found between the individual time for PFS and the expression of both ERCC1 (R = −0.36, p = 0.015) and ABRX (R = −0.46, p = 0.001). Patients with low ERCC1 expression had a longer OS as compared to patients with high ERCC1 expression (HR = 0.26, log-rank p = 0.02).

Conclusions

The study confirms tumor expression of ERCC1 as a predictor for clinical outcome in patients with advanced NSCLC receiving platinum-based chemotherapy, and found ABRX expression to be similarly predictive of clinical outcome. Prospective validation is warranted and - if confirmed - non platinum-containing chemotherapy should be explored as the preferred treatment in patients with high ERCC1 or ABRX expression and no activating mutations of EGFR.     

A phase II trial of induction chemotherapy followed by continuous hyperfractionated accelerated radiotherapy in locally advanced non-small-cell lung cancer

Background and purpose

We conducted a phase II study combining induction chemotherapy with continuous hyperfractionated accelerated radiotherapy (CHART) in locally advanced non-small-cell lung cancer (NSCLC).

Materials and methods

A total of 40 patients with stage III NSCLC were enrolled. All patients received 3 cycles of chemotherapy followed by CHART (56 Gy in 36 fractions over 12 days). The primary outcome measure was radiation toxicity. Secondary endpoints were response rate, overall survival, disease-free survival and loco-regional progression-free survival.

Results

Acute radiation toxicity was minimal and there were no significant late toxicities. The response rate after completion of chemoradiation was 65%. The median and 2-year overall survival, progression-free survival and loco-regional progression-free survivals were 15.7 months, 28%; 12.1 months, 23%; and 26.4 months, 51%, respectively.

Conclusions

Induction chemotherapy can be safely combined with CHART. The survival results are consistent with previous studies of chemotherapy followed by accelerated radiotherapy. This approach should be compared with synchronous chemoradiation to determine if it represents a less toxic alternative.     

Concurrent and adjuvant docetaxel with three-dimensional conformal radiation therapy plus androgen deprivation for high-risk prostate cancer: Preliminary results of a multicentre phase II trial

Background and purpose

We evaluate the feasibility of concomitant and adjuvant docetaxel combined with three-dimensional conformal radiotherapy (3D-CRT) and androgen deprivation in high-risk prostate carcinomas.

Methods

Fifty men with high-risk localized prostate cancer (16), locally advanced (28) or very high-risk prostate cancer (6) were included. Seventy Gy were delivered on prostate and seminal vesicles in 35 fractions, concurrently with weekly docetaxel (20 mg/m²). Three weeks after the completion of 3D-CRT, docetaxel was given for 3 cycles (60 mg/m²), every 3 weeks. Patients had to receive LHRH agonist during 3 years.

Results

The intent to treat analysis shows that four patients out of 15 stopped prematurely the chemotherapy due to grade 3-4 acute toxicity. In the per protocol analysis, 46 patients completed a full-dose chemoradiation regimen representing 413 cycles: five patients experienced a grade 3 toxicity, and 15 patients experienced a grade 2 toxicity. With a median follow-up of 54 months, the 5-year clinical disease-free survival was 66.72% and the 5-year survival was 92.15%.

Conclusions

3D-CRT with androgen deprivation and concurrent weekly docetaxel, followed by three cycles of adjuvant docetaxel may be considered as feasible in high-risk prostate cancer and deserved to be evaluated in a phase III randomized trial.     

Dose escalation in the radiotherapy of non-small-cell lung cancer with aperture-based intensity modulation and photon beam energy optimization for non-preselected patients

Purpose

To verify the potential of aperture-based intensity-modulated radiotherapy (AB-IMRT) to realize dose escalation plans for non-preselected non-small-cell lung cancer (NSCLC) patients, using photon beam energy optimization.

Methods and materials

Seven cases of NSCLC were retrospectively studied. Clinical reference plans were made at 60 Gy by an experienced dosimetrist. Dose escalation was applied to PTV2, a subvolume within the main PTV1. Escalation plans were optimized by considering beam angles (table and gantry), energy (6 and 23 MV) and weights, for an increasing dose to the PTV2, starting from 66 Gy and keeping 30 fractions.

Results

In five cases, doses over 78 Gy could be achieved before exceeding organs at risk (OARs) standard tolerance. Peripheral overdosages, as well as lung and spinal cord tolerance doses, limited escalation. Means ± SD V_95% parameters were (97.3 ± 0.9)% for PTV1s and (96.7 ± 2.2)% for PTV2s. Doses to OARs were also maintained at acceptable levels. Optimized plans made use of both low- and high-energy beams and had a similar number of monitor units compared to the 60 Gy clinical plans.

Conclusions

The AB-IMRT system can successfully realize dose escalation for a sizeable number of cases. Plans produced contained few large segments, and are applicable to a wide range of tumor volumes and locations.     

Volumetric modulated arc therapy (VMAT) vs. serial tomotherapy, step-and-shoot IMRT and 3D-conformal RT for treatment of prostate cancer

Introduction

Volumetric modulated arc therapy (VMAT), a complex treatment strategy for intensity-modulated radiation therapy, may increase treatment efficiency and has recently been established clinically. This analysis compares VMAT against established IMRT and 3D-conformal radiation therapy (3D-CRT) delivery techniques.

Methods

Based on CT datasets of 9 patients treated for prostate cancer step-and-shoot IMRT, serial tomotherapy (MIMiC), 3D-CRT and VMAT were compared with regard to plan quality and treatment efficiency. Two VMAT approaches (one rotation (VMAT1x) and one rotation plus a second 200° rotation (VMAT2x)) were calculated for the plan comparison. Plan quality was assessed by calculating homogeneity and conformity index (HI and CI), dose to normal tissue (non-target) and D_95% (dose encompassing 95% of the target volume). For plan efficiency evaluation, treatment time and number of monitor units (MU) were considered.

Results

For MIMiC/IMRT_MLC/VMAT2x/VMAT1x/3D-CRT, mean CI was 1.5/1.23/1.45/1.51/1.46 and HI was 1.19/1.1/1.09/1.11/1.04. For a prescribed dose of 76 Gy, mean doses to organs-at-risk (OAR) were 50.69 Gy/53.99 Gy/60.29 Gy/61.59 Gy/66.33 Gy for the anterior half of the rectum and 31.85 Gy/34.89 Gy/38.75 Gy/38.57 Gy/55.43 Gy for the posterior rectum. Volumes of non-target normal tissue receiving ?70% of prescribed dose (53 Gy) were 337 ml/284 ml/482 ml/505 ml/414 ml, for ? 50% (38 Gy) 869 ml/933 ml/1155 ml/1231 ml/1993 ml and for ? 30% (23 Gy) 2819 ml/3414 ml/3340 ml/3438 ml /3061 ml. D_95% was 69.79 Gy/70.51 Gy/71,7 Gy/71.59 Gy/73.42 Gy. Mean treatment time was 12 min/6 min/3.7 min/1.8 min/2.5 min.

Conclusion

All approaches yield treatment plans of improved quality when compared to 3D-conformal treatments, with serial tomotherapy providing best OAR sparing and VMAT being the most efficient treatment option in our comparison. Plans which were calculated with 3D-CRT provided good target coverage but resulted in higher dose to the rectum.     

Randomized phase II study of gefitinib versus erlotinib in patients with advanced non-small cell lung cancer who failed previous chemotherapy

Purpose

Gefitinib and erlotinib are potent EGFR TKIs, with antitumor activity. In this randomized, single-center, non-comparative phase II trial, the efficacy and safety of gefitinib and erlotinib was evaluated as the second-line therapy for advanced non-small cell lung cancer (NSCLC).

Patients and methods

Patients with locally advanced, metastatic stage IIIB/IV NSCLC who failed first-line chemotherapy and had either EGFR mutation or at least two out of three clinical factors associated with higher incidence of EGFR mutations (female, adenocarcinoma histology, and never-smoker) were eligible.

Results

A total of 96 (48 per arm) patients were randomly assigned to gefitinib- or erlotinib-arm, respectively. Baseline characteristics were well-balanced between the two arms. The response rates (RR) were 47.9% in the gefitinib arm and 39.6% in the erlotinib arm. Median PFS was 4.9 months (95% CI, 1.3-8.5) in the gefitinib arm and 3.1 months (95% CI, 0.0-6.4) in the erlotinib arm. The most common grade 3/4 toxicity was skin rash. Exploratory analyses showed that there was no significant difference in RR and PFS in the gefitinib arm compared to the erlotinib arm (RR (%) 47.9 vs. 39.6, p = 0.269; median survival (months) 4.9 vs. 3.1, p = 0.336). There was no significant difference in QOL between the two arms.

Conclusion

Both gefitinib and erlotinib showed effective activity and tolerable toxicity profiles as second-line treatment for the selected population of NSCLC. We may consider conducting a phase III trial to directly compare the efficacy and toxicity between gefitinib and erlotinib in an enriched patient population.     

Dose painting by contours versus dose painting by numbers for stage II/III lung cancer: Practical implications of using a broad or sharp brush

Purpose

Local recurrence rates are high in patients with locally advanced NSCLC treated with 60 to 66 Gy in 2 Gy fractions. It is hypothesised that boosting volumes with high SUV on the pre-treatment FDG-PET scan potentially increases local control while maintaining acceptable toxicity levels. We compared two approaches: threshold-based dose painting by contours (DPBC) with voxel-based dose painting by numbers (DPBN).

Materials and methods

Two dose painted plans were generated for 10 stage II/III NSCLC patients with 66 Gy at 2-Gy fractions to the entire PTV and a boost dose to the high SUV areas within the primary GTV. DPBC aims for a uniform boost dose at the volume encompassing the SUV 50%-region (GTV_boost). DPBN aims for a linear relationship between the boost dose to a voxel and the underlying SUV. For both approaches the boost dose was escalated up to 130 Gy (in 33 fractions) or until the dose limiting constraint of an organ at risk was met.

Results

For three patients (with relatively small peripheral tumours) the dose within the GTV could be boosted to 130 Gy using both strategies. For the remaining patients the boost dose was confined by a critical structure (mediastinal structures in six patients, lungs in one patient). In general the amount of large brush DPBC boosting is limited whenever the GTV_boost is close to any serial risk organ. In contrast, small brush DPBN inherently boosts at a voxel-by-voxel basis allowing significant higher dose values to high SUV voxels more distant from the organs at risk. We found that the biological SUV gradients are reasonably congruent with the dose gradients that standard linear accelerators can deliver.

Conclusions

Both large brush DPBC and sharp brush DPBN techniques can be used to considerably boost the dose to the FDG avid regions. However, significantly higher boost levels can be obtained using sharp brush DPBN although sometimes at the cost of a less increased dose to the low SUV regions.     

Wnt3 gene expression promotes tumor progression in non-small cell lung cancer

Background

Recent studies have shown that human copper transporter 1 (hCtr1), the major copper influx transporter, is involved in the transport of platinum-based antitumor agents. We investigated the predictive and prognostic values of hCtr1, and copper efflux transporters ATP7A and ATP7B, in patients with locally advanced non-small cell lung cancer (NSCLC) receiving first-line platinum-based chemotherapy.

Methods

From 2004 to 2009, we identified 54 consecutive stage III NSCLC patients who underwent first-line platinum-based doublet chemotherapy. Immunohistochemical studies of hCtr1, ATP7A and ATP7B on the paraffin-embedded pre-treatment tumor samples were performed and correlated with chemotherapy response and survival.

Results

Overexpression of hCtr1, ATP7A and ATP7B were observed in 68%, 48% and 74% of the participants, respectively. hCtr1 overexpression was associated with better chemotherapy responses (P < 0.01); whereas ATP7A and ATP7B were not. Patients with hCtr1 overexpressing tumors had better progression-free survival (PFS) and overall survival (OS) (P = 0.01 and 0.047, respectively). In multivariate analyses for chemotherapy response and PFS, only hCtr1 overexpression emerged as a favorable independent predictive and prognostic factor (all P < 0.01).

Conclusion

This is the first report to state that hCtr1 is not only an independent predictor of platinum-based chemotherapy response but also a prognostic factor in stage III NSCLC.     

Durable palliation of breast cancer chest wall recurrence with radiation therapy, hyperthermia, and chemotherapy

Background and purpose

Chest wall recurrences of breast cancer are a therapeutic challenge and durable local control is difficult to achieve. Our objective was to determine the local progression free survival (LPFS) and toxicity of thermochemoradiotherapy (ThChRT) for chest wall recurrence.

Methods

Twenty-seven patients received ThChRT for chest wall failure from 2/1995 to 6/2007 and make up this retrospective series. All received concurrent superficial hyperthermia twice weekly (median 8 sessions), chemotherapy (capecitabine in 21, vinorelbine in 2, and paclitaxel in 4), and radiation (median 45 Gy). Patients were followed up every 1.5-3 months and responses were graded with RECIST criteria and toxicities with the NCI CTC v4.0.

Results

Twenty-three (85%) patients were previously irradiated (median 60.4 Gy) and 22 (81%) patients received prior chemotherapy. Median follow-up was 11 months. Complete response (CR) was achieved in 16/20 (80%) of patients with follow-up data, and 1 year LPFS was 76%. Overall survival was 23 months for patients with CR, and 5.4 months in patients achieving a partial response (PR) (p = 0.01). Twenty-two patients experienced acute grade 1/2 treatment related toxicities, primarily moist desquamation. Two patients experienced 3rd degree burns; all resolved with conservative measures.

Conclusions

ThChRT offers durable palliation and prolonged LPFS with tolerable acute toxicity, especially if CR is achieved.     

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.     

Under usage of zoledronic acid in non-small cell lung cancer patients with metastatic bone disease--a short communication

Background and aim

The use of zoledronic acid (ZA) is now recommended for patients with NSCLC and metastatic bone disease (MBD). We thus examined the rates of ZA administration in NSCLC looking specifically at the use of this drug with systemic chemotherapy (ZCt) and comparing overall survival between patients who had ZCt from diagnosis to those who had chemotherapy (Ct) alone.

Method

In this retrospective audit, we analysed the data of 114 consecutive patients with stage IV NSCLC and MBD at presentation. Forty-three of these patients had received zoledronic acid and chemotherapy (ZCt) and 71 had received chemotherapy alone (Ct).

Results

Forty-three (37.7%, 43/114) of NSCLC patients diagnosed with MBD received ZA with their first chemotherapy (ZCt). Patients on ZCt, after adjustment for the planned prognostic factors (sites of disease, histology and PS), had better overall survival (OS), with a median of 34 weeks, compared to those who received chemotherapy alone, who had a median of 19 weeks (p = 0.03), HR = 0.60 (95%CI: 0.38-0.96). After adjusting for prognostic factors (sex, age. single versus doublet chemotherapy), ZCt patients still maintained a trend to better OS (p = 0.06) HR 0.63 (95%CI: 0.39-1.02) 34 versus 21 weeks.

Conclusions

The percentage of patients with MBD treated with ZA at first chemotherapy (37.7%) is low. The addition of ZA increased OS in NSCLC patients with MBD in this audit. More formal policies and dedicated trials on the treatment of MBD in NSCLC patients need to be put in place.     

Concurrent cetuximab and radiotherapy after docetaxel-cisplatin induction chemotherapy in stage III NSCLC: Satellite—A phase II study from the Swedish Lung Cancer Study Group

Background

Several attempts to increase the locoregional control in locally advanced lung cancer including concurrent chemotherapy, accelerated fractionation and dose escalation have been made during the last years. As the EGFR directed antibody cetuximab has shown activity concurrent with radiotherapy in squamous cell carcinoma of the head and neck, as well as in stage IV NSCLC combined with chemotherapy, we wanted to investigate radiotherapy with concurrent cetuximab in locally advanced NSCLC, a tumour type often over expressing the EGF-receptor.

Methods

Between February 2006 and August 2007 75 patients in stage III NSCLC with good performance status (PS 0 or 1) and adequate lung function (FEV1 > 1.0) were enrolled in this phase II study at eight institutions. Treatment consisted of 2 cycles of induction chemotherapy, docetaxel 75 mg/m² and cisplatin 75 mg/m² with 3 weeks interval. An initial dose of cetuximab 400 mg/m² was given before start of 3D-CRT to 68 Gy with 2 Gy per fraction in 7 weeks concurrent with weekly cetuximab 250 mg/m². Toxicity was scored weekly during radiotherapy (CTC 3.0), and after treatment the patients were followed every third month with CT-scans, toxicity scoring and QLQ.

Results

Seventy-one patients were eligible for analysis as four were incorrectly enrolled. Histology: adenocarcinoma 49%, squamous cell carcinoma 39% and other NSCLC 12%. The majority had PS 0 (62.5%), median age 62.2 (42-81), 50% were women and 37% had a pre-treatment weight loss > 5%. Toxicity: esophagitis grade 1-2: 72%; grade 3: 1.4%. Hypersensitivity reactions grade 3-4: 5.6%. Febrile neutropenia grade 3-4: 15.4%. Skin reactions grade 1-2: 74%; grade 3: 4.2%. Diarrhoea grade 1-2: 38%; grade 3: 11.3%. Pneumonitis grade 1-2: 26.8%; grade 3: 4.2%; grade 5: 1.4%. The median follow-up was 39 months for patients alive and the median survival was 17 months with a 1-, 2- and 3-year OS of 66%, 37% and 29% respectively. Until now local or regional failure has occurred in 20 patients and 22 patients have developed distant metastases. Weight loss, PS and stage were predictive for survival in univariate as well as in multivariate analysis.

Conclusion

Induction chemotherapy followed by concurrent cetuximab and RT to 68 Gy is clearly feasible with promising survival. Toxicity, e.g. pneumonitis and esophagitis is low compared to most schedules with concurrent chemotherapy. This treatment strategy should be evaluated in a randomised manner vs. concurrent chemoradiotherapy to find out if it is a valid treatment option.     

DNA methylation changes in cells regrowing after fractioned ionizing radiation

Background and purpose

Repeated exposure to ionizing radiation (IR) can result in adaptive reactions. While DNA methylation changes in adaption to repeated stress exposure are established for a variety of drugs, their role in fractioned ionizing radiation is largely unknown.

Material and methods

MCF7 breast cancer cells were treated 5 times a week with IR in fractions of 2 Gy, resulting in total doses of 10 and 20 Gy. Cells were harvested 48 and 72 h after the last irradiation, as well as after a recovery period of at least 14 d. To identify genes differentially methylated in irradiated versus non-irradiated cells, we used methyl-CpG immunoprecipitation (MCIp) followed by global methylation profiling on CpG island microarrays.

Results

MCIp profiling revealed methylation changes in several CpG islands 48 h after FIR with 10 and 20 Gy. Cells receiving a total dose of 10 Gy started regrowing after 14 d and exhibited similar radioresistance as mock-treated cells. Differential methylation of the CpG units associated with FOXC1 (p < 0.001) and TRAPPC9 (p < 0.001) could be confirmed by time-of-flight mass spectrometry (Sequenom).

Conclusions

In summary, these data indicate that regrowth of MCF7 cells after 10 Gy FIR is associated with locus-specific alterations in DNA methylation.     

Predictive factors of gastroduodenal toxicity in cirrhotic patients after three-dimensional conformal radiotherapy for hepatocellular carcinoma

Background and purpose

To identify predictive factors for the development of gastroduodenal toxicity (GDT) in cirrhotic patients treated with three-dimensional conformal radiotherapy (3D-CRT) for hepatocellular carcinoma (HCC).

Materials and methods

We retrospectively analyzed dose-volume histograms (DVHs) and clinical records of 73 cirrhotic patients treated with 3D-CRT for HCC. The median radiation dose was 36 Gy (range, 30-54 Gy) with a daily dose of 3 Gy. The grade of GDT was defined by the Common Toxicity Criteria Version 2. The predictive factors of grade 3 GDT were identified.

Results

Grade 3 GDT was found in 9 patients. Patient’s age and the percentage of gastroduodenal volume receiving more than 35 Gy (V₃₅) significantly affected the development of grade 3 GDT. Patients over 50 years of age developed grade 3 GDT more frequently than patients under 50 years of age. The risk of grade 3 GDT grew exponentially as V₃₅ increased. The 1-year actuarial rate of grade 3 GDT in patients with V₃₅ < 5% is significantly lower than that in patients with a V₃₅ ?5% (4% vs. 48%, p < .01).

Conclusions

Patient’s age and V₃₅ were the most predictive factors for the development of grade 3 GDT in patients treated with RT.     

Bowel exposure in rectal cancer IMRT using prone, supine, or a belly board

Purpose

To investigate bowel exposure using prone, supine, or two different belly boards for rectal cancer intensity modulated RT plans using a full bladder protocol.

Methods and materials

For 11 volunteers four MR scans were acquired, on a flat table in prone, supine, and on two different belly boards (IT-V Medizintechnik GmbH® (BB1) and CIVCO® (BB2)), using a full bladder protocol. On each scan a 25 × 2 Gy IMRT plan was calculated.

Results

BB2 led to an average bowel area volume reduction of 20-30% at any dose level compared to prone. BB1 showed a smaller dose reduction effect, while no differences between prone and supine were found. Differences between BB2 and prone, supine or BB1 were significant up to a level of respectively, 45, 35, and 30 Gy. The reducing effect varied among individuals, except for the 50 Gy region, where no effect was found. An increase in bladder volume of 100 cc led to a significant bowel area V15 reduction of 16% independent of scan type.

Conclusions

In the low and intermediate dose region a belly board still attributes to a significant bowel dose reduction when using IMRT and a full bladder protocol. A larger bladder volume resulted in a significant decreased bowel area dose.     

Positive urinary cytology in patients with lung cancer in the absence of obvious urine tract metastases

Purpose

To study the phenomenon of positive urine cytology in patients with lung cancer in the absence of obvious urothelial metastases.

Patients and methods

150 patients with small (SCLC) and non-small cell lung cancer (NSCLC) of all stages and 3 control groups were prospectively studied. Immunocytochemical study (cytokeratins 7-20, TTF1) in all positive urine specimens and chemokine profile (CXCR4, CCL21) study of the primary tumor in selected positive patients was performed. In experimental study, C57Bl/6 BALB/C mice injected with LLC lung and 4T1 mammary cancer cells were used for the detection of positive urine cytology.

Results

11% of patients with NSCLC, 7% of patients with SCLC and none of the control group had positive urine cytology. In NSCLC, metastatic disease and high tumor burden positively correlated (p = 0.01 and 0.03 respectively) with the phenomenon. In SCLC, correlation with extensive disease and multiple metastatic sites (p = 0.02 and 0.04 respectively) was found. No correlation was found in either group with: age, gender, histology, performance status, line of chemotherapy, previous platinum-based chemotherapy, adrenal metastases, renal function, abnormal urinary sediment, response to chemotherapy and overall survival (p = 0.9). Distinctive chemokine expression was identified in positive patients studied and was not observed in negative patients (×2 p = 0.008). In the experimental study, only the LLC lung cancer cells were detected in the urine cytology of mice.

Conclusion

This phenomenon, carrying undefined pathophysiological mechanisms, seems to characterize only patients with metastatic/extensive disease and high tumor burden. Further studies are needed to validate our preliminary chemokine expression results.     

Details of recurrence sites after elective nodal irradiation (ENI) using 3D-conformal radiotherapy (3D-CRT) combined with chemotherapy for thoracic esophageal squamous cell carcinoma - A retrospective analysis

Purpose

To describe patterns of recurrence of elective nodal irradiation (ENI) in definitive chemoradiotherapy (CRT) for thoracic esophageal squamous cell carcinoma (SqCC) using 3D-conformal radiotherapy.

Methods and materials

One hundred and twenty-six consecutive patients with stages I-IVB thoracic esophageal SqCC newly diagnosed between June 2000 and July 2009 and treated with 3D-CRT in our institution were recruited from our database. Definitive CRT consisted of two cycles of nedaplatin/5FU repeated every 4 weeks, with concurrent radiation therapy of 50-50.4 Gy in 25-28 fractions. Until completion, radiotherapy was delivered to the N1 and M1a lymph nodes as ENI in addition to gross tumor volume.

Results

All 126 patients were included in this analysis, and their tumors were staged as follows: T1/T2/T3/T4, 28/18/54/26; N0/N1, 50/76; M0/M1a/M1b, 91/5/30. The mean follow-up period for the 63 surviving patients was 28.3 (±22.8) months. Eighty-seven patients (69%) achieved complete response (CR) without any residual tumor at least once after completion of CRT. After achieving CR, each of 40 patients experienced failures (local = 20 and distant = 20) and no patient experienced elective nodal failure without having any other site of recurrence. The upper thoracic esophageal carcinoma showed significantly more (34%) relapses at the local site than the middle (9%) or lower thoracic (11%) carcinomas. The 2-year and 3-year overall survival was 56% and 43%, respectively. The 1-year, 2-year and 3-year disease-free survival was 46%, 38% and 33%, respectively.

Conclusions

In CRT for esophageal SqCC, ENI was effective for preventing regional nodal failure. The upper thoracic esophageal carcinomas had significantly more local recurrences than the middle or lower thoracic sites.     

Concurrent doxorubicin and radiotherapy for anaplastic thyroid cancer: A critical re-evaluation including uniform pathologic review

Background and purpose

Anaplastic thyroid carcinoma (ATC) is a rare, aggressive malignancy. The potential for pathologic misclassification complicates interpretation of published data. One standard treatment option for locoregionally advanced disease is weekly low-dose doxorubicin with concurrent radiation therapy, and was previously developed at our institution. We evaluated our more recent experience with this approach, which included pathologic confirmation of all cases.

Materials and methods

A retrospective review was performed on patients identified through the Memorial Sloan-Kettering Cancer Center (MSKCC) Cancer Database. Inclusion criteria: pathologically confirmed ATC; locoregional disease encompassable within a radiation portal; treatment with curative intent at MSKCC with planned weekly doxorubicin (10 mg/m²) and concurrent radiation. Principle outcomes assessed were locoregional progression-free survival (LR-PFS) and overall survival (OS).

Results

Thirty-seven patients were included. Median radiotherapy dose was 57.6 Gy, and was ?50 Gy in 29 (78%), administered through hyperfractionated or once-daily schedules. One-year outcomes were LR-PFS, 45%; OS, 28%.

Conclusion

The prognosis of patients with ATC remains grim and our current results appear inferior to those reported previously by our institution. More accurate histologic diagnoses and patient selection in the present series compared to the prior one may be responsible in part. Better therapy is desperately needed for this aggressive disease.     

Stereotactic radiotherapy of histologically proven inoperable stage I non-small cell lung cancer: Patterns of failure

Background and purpose

To report patterns of failure of stereotactic body radiation therapy (SBRT) in inoperable patients with histologically confirmed stage I NSCLC.

Materials and methods

Ninety-two inoperable patients (median age: 75 years) with clinically staged, histologically proven T1 (n = 31) or T2 (n = 61), N0, M0 non-small cell lung cancer (NSCLC) were included in this study. Treatment consisted of 3-5 fractions with 7-15 Gy per fraction prescribed to the 60% isodose.

Results

Freedom from local recurrence at 1, 3 and 5 years was 89%, 83% and 83%, respectively. All 10 local failures were observed in patients with T2 tumors. Isolated regional recurrence was observed in 7.6%. The crude rate of distant progression was 20.7%. Overall survival at 1, 3, and 5 years was 79%, 38% and 17% with a median survival of 29 months. Disease specific survival at 1, 3, and 5 years was 93%, 64% and 48%. Karnofsky performance status, T stage, gross tumor volume and tumor location had no significant impact on overall and disease specific survival. SBRT was generally well tolerated and all patients completed therapy as planned.

Conclusion

SBRT for stage I lung cancer is very well tolerated in this patient cohort with significant cardiopulmonal comorbidity and results in excellent local control rates, although a considerable portion develops regional and distant metastases.