Preoperative radiotherapy and local excision of rectal cancer with immediate radical re-operation for poor responders

Background and purpose

To report an early analysis of prospective study exploring preoperative radiotherapy and local excision in rectal cancer.

Materials and methods

Mucosa at tumour edges was tattooed. Patients with cT1-3N0 tumour <3-4 cm were treated with either 5 × 5 Gy + 4 Gy boost (N = 31) or chemoradiation (50.4 Gy + 5.4 Gy boost, 1.8 Gy per fraction + 5-fluorouracyl and leucovorin; N = 13). Thirteen patients from the short-course group were unfit for chemotherapy. The interval from radiation to full-thickness local excision was 6 weeks. The protocol called for conversion to a transabdominal surgery in case of ypT2-3 disease or positive margin.

Results

The postoperative complications requiring hospitalization were recorded in 9% of patients. The rate of pathological complete response was 41%. The rate of patients requiring conversion was 34%; however, 18% actually underwent conversion and the remaining 16% refused or were unfit. During the 14 months of median follow-up, local recurrence was detected in 7% of patients and all underwent salvage surgery. Of 19 patients in whom initially anterior resection was likely, 16% had abdominoperineal resection performed for a conversion or as a rescue procedure.

Conclusion

Our study suggests that the short-course radiation prior to local excision is a treatment option for high-risk patients.     

Long-term results of concurrent radiotherapy and UFT in patients with locally advanced pancreatic cancer

Background

Definition and treatment options for locally advanced non-resectable pancreatic cancer (LAPC) vary. Treatment options range from palliative chemotherapy to chemoradiotherapy (CRT). Several studies have shown that a number of patients become resectable after complementary treatment prior to surgery.

Methods

From 2001 to 2005, 63 consecutive patients with unresectable LAPC received CRT. CRT was given at a dose of 50 Gy/27 fractions, combined with UFT (300 mg/m²/day) and folinic acid. Re-evaluation of resectability was planned 4-6 weeks after completion of CRT.

Results

Fifty-eight patients completed all 27 treatment fractions. Toxicity was generally mild, with 18 patients experiencing CTCAE grade 3 or worse acute reactions. One patient died following a treatment-related infection. Two patients developed grade 4 upper GI bleeding. Median survival was 10.6 (8-13) months. Eleven patients underwent resection, leading to a resection rate of 17%, and a median survival of 46 (23-nr) months. All 11 patients had a R0 resection. Median survival for the patients not resected was 8.8 (8-12) months.

Conclusion

CRT with 50 Gy combined with UFT, is a well-tolerated and effective treatment for patients with LAPC. R0 resection was possible in 17% leading to a long median survival of 46 months in resected patients.     

Significance of an exon 2 G4C14-to-A4T14 polymorphism in the p73 gene on survival in rectal cancer patients with or without preoperative radiotherapy

Background and purpose

An exon 2 G4C14 → A4T14 polymorphism in the p73 gene was shown to be related to survival in several types of cancers, including colorectal cancer. The purpose was to investigate if this polymorphism was related to survival in rectal cancer patients with or without preoperative radiotherapy.

Materials and methods

DNA extracted from tissue of 138 rectal cancer patients that received preoperative radiotherapy or had surgery alone was typed for the polymorphism by PCR using confronting two-pair primers.

Results

Among patients, 69% had GC/GC genotype, 27% had GC/AT and 4% had AT/AT. In the radiotherapy group, patients carrying the AT (GC/AT + AT/AT) allele had stronger expression of p53 (p = 0.001) and survivin protein (p = 0.03) than those carrying the GC/GC genotype. Further, among patients receiving preoperative radiotherapy the GC/GC genotype tended to be related to better survival (p = 0.20). Patients with GC/GC genotype, along with negative p53 and weak survivin expression showed better survival than the other patients (p = 0.03), even after adjusting for TNM stage and tumor differentiation (p = 0.01, RR, 7.63, 95% CI, 1.50-38.74). In the non-radiotherapy group, the polymorphism was not related to survival (p = 0.74).

Conclusions

Results suggest that the p73 G4C14 → A4T14 polymorphism could be one factor influencing outcome of preoperative radiotherapy in rectal cancer patients.     

Target volume shape variation during hypo-fractionated preoperative irradiation of rectal cancer patients

Purpose

To quantify the day-to-day target volume shape variation in rectal-cancer patients treated with preoperative 5 × 5 Gy radiotherapy.

Materials and methods

For 27 patients a prone position plan-CT (pCT) and five daily pre-treatment cone-beam-CT (CBCT) scans were acquired. A sub-region of the CTV (MesoRect, anus up to the cranial end of the mesorectal-fascia) was delineated on all scans. The MesoRect deformation was quantified by the distance between pCT- and CBCT-delineations and was stored in surface-maps. Finally, the influence of bladder and rectum filling on MesoRect deformation was evaluated. Data were analyzed for male and female patients separately.

Results

A large range of systematic and random deformations, 1-7 mm (1SD), on different areas of the MesoRect were found. The maximum deformations were located at the upper-anterior-side of the MesoRect. For females the errors were up to 3 mm larger than for males. Small correlations, r² ? 0.4, were found with changes in bladder volume. Larger correlations, r² ? 0.7, were found for rectal volume in a distinctive area in the upper-half of the MesoRect.

Conclusions

Substantial and heterogeneous deformations of the MesoRect were found. Therefore different PTV margins in positions along the cranio-caudal axis, in the anterior-posterior direction. Margins should also be larger for female patients compared to male patients.     

Phase 2 trial of linifanib (ABT-869) in patients with advanced renal cell cancer after sunitinib failure

Purpose

This study assessed the efficacy and safety of linifanib in patients with advanced renal cell carcinoma (RCC) who were previously treated with sunitinib.

Materials and methods

This open-label, multicentre, phase 2 trial of oral linifanib 0.25 mg/kg/day enrolled patients who had prior nephrectomy and adequate organ function. The primary end-point was objective response rate (ORR) per response evaluation criteria in solid tumors (RECIST) by central imaging. Secondary end-points were progression-free survival (PFS), overall survival (OS) and time to progression (TTP). Safety was also assessed.

Results

Fifty-three patients, median age 61 years (range 40-80) were enrolled (August 2007 to October 2008) across 12 North-American centres. Median number of prior therapies was 2 (range 1-4); 43 patients (81%) had clear-cell histology. ORR was 13.2%, median PFS was 5.4 months (95% Confidence Interval (CI): 3.6, 6.0) and TTP was the same; median OS was 14.5 months (95% CI: 10.8, 24.1). The most common treatment-related adverse events (AEs) were diarrhoea (74%), fatigue (74%) and hypertension (66%), and the most common treatment-related Grade 3/4 AE was hypertension (40%).

Conclusions

Linifanib demonstrated clinically meaningful activity in patients with advanced RCC after sunitinib failure. At 0.25 mg/kg/day, significant dose modifications were required. An alternative, fixed-dosing strategy is being evaluated in other trials.     

Dosimetry audit for a multi-centre IMRT head and neck trial

Background and purpose

PARSPORT was a multi-centre randomised trial in the UK which compared Intensity-Modulated Radiotherapy (IMRT) and conventional radiotherapy (CRT) for patients with head and neck cancer. The dosimetry audit goals were to verify the plan delivery in participating centres, ascertain what tolerances were suitable for head and neck IMRT trials and develop an IMRT credentialing program.

Materials and methods

Centres enrolling patients underwent rigorous quality assurance before joining the trial. Following this each centre was visited for a dosimetry audit, which consisted of treatment planning system tests, fluence verification films, combined field films and dose point measurements.

Results

Mean dose point measurements were made at six centres. For the primary planning target volume (PTV) the differences with the planned values for the IMRT and CRT arms were −0.6% (1.8% to −2.4%) and 0.7% (2.0% to −0.9%), respectively. Ninety-four percent of the IMRT fluence films for individual fields passed gamma criterion of 3%/3 mm and 75% of the films for combined fields passed gamma criterion 4%/3 mm (no significant difference between dynamic delivery and step and shoot delivery).

Conclusions

This audit suggests that a 3% tolerance could be applied for PTV point doses. For dose distributions tolerances of 3%/3 mm on individual fields and 4%/3 mm for combined fields are proposed for multi-centre head and neck IMRT trials.     

A randomized phase II study of cisplatin/5-FU concurrent chemoradiotherapy for esophageal cancer: Short-term infusion versus protracted infusion chemotherapy (KROSG0101/JROSG021)

Purpose

A randomized phase II study was conducted to compare the toxicity and efficacy of combining short-term chemotherapy (CT) or protracted CT with radiotherapy (RT) for esophageal cancer.

Materials and methods

Eligible patients were <75 years and with performance status (PS) of 0-2, and had stages II-IVA esophageal cancer. Two cycles of cisplatin 70 mg/m² for 1 day and 5FU 700 mg/m² for 5 days (arm A) or cisplatin 7 mg/m² for 10 days and 5FU 250 mg/m² for 14 days (arm B) were given with RT of 60 Gy/30 fractions/7 weeks (1-week split).

Results

Of 91 patients enrolled, 46 were randomized to arm A and 45 to arm B. Two cycles of CT were given concurrently with RT for 89% in arm A and for 71% in arm B with significant difference (P = .031). The 2- and 5-year overall survival rates for arm A were 46% and 35%, while those for arm B were 44% and 24%, respectively, without significant difference. The 2- and 5-year progression-free survival rates for arm A were 30% and 30%, while those for arm B were 29% and 12%, respectively.

Conclusions

Protracted infusion CT with RT provides no advantage over standard short-term infusion CT with RT for esophageal cancer.     

End of life care in adolescents and young adults with cancer: experience of the adolescent unit of the Institut Gustave Roussy

Background

Cancer is the third leading cause of death in adolescents and young adults (AYA). Little is known, however, about how end-of-life unfolds for those who die of progressive disease. In order to better evaluate the specific needs of these patients, we performed this study providing baseline information about end-of-life care patterns for AYA in our department.

Patients

A standardised form was used to collect data concerning all 45 patients treated for a malignancy in the Paediatric and Adolescent Oncology Department at the Gustave Roussy Institute, and who had died of progressive disease above 13 years of age, over a two-year period.

Results

The main diagnoses were sarcomas and brain tumours. Previous cancer-directed treatment included a median of 3 different chemotherapy regimens, high-dose chemotherapy with haematopoietic stem cell support for 13% and radiotherapy for 40%. One in every four patients had been enrolled in a clinical trial at diagnosis. Median survival was 18 months after the diagnosis and 7 months after the first relapse/progression. During the last week of life, the median number of physical symptoms was 4, mostly pain and dyspnoea. Frequent psychological symptoms were sadness, anxiety, fear and guilt. End-of-life care included transfusions, artificial nutrition, corticosteroids, pain control, sedation but also palliative chemotherapy. The median time spent in hospital during the last month of life was 16 days. Most patients had died in hospital.

Conclusions

The terminally ill adolescent displays notable challenges to care providers and requires a holistic approach with the help of a multidisciplinary team.     

Gefitinib plus cisplatin and radiotherapy in previously untreated head and neck squamous cell carcinoma: A phase II, randomized, double-blind, placebo-controlled study

Background and purpose

To assess the efficacy and safety of gefitinib given concomitantly and/or as maintenance therapy to standard cisplatin/radiotherapy for previously untreated, unresected, stage III/IV non-metastatic SCCHN.

Materials and methods

In this phase II, double-blind, study, 226 patients were randomized to gefitinib 250 mg/day, 500 mg/day or placebo in two phases: a concomitant phase (gefitinib or placebo with chemoradiotherapy), followed by a maintenance phase (gefitinib or placebo alone). Primary endpoint was local disease control rate (LDCR) at 2 years; secondary endpoints were LDCR at 1 year, objective response rate, progression-free survival, overall survival, and safety and tolerability.

Results

Gefitinib (250 and 500 mg/day) did not improve 2-year LDCR compared with placebo either when given concomitantly with chemoradiotherapy (32.7% vs. 33.6%, respectively; OR 0.921, 95% CI 0.508, 1.670 [1-sided p = 0.607]) or as maintenance therapy (28.8% vs. 37.4%, respectively; OR 0.684, 95% CI 0.377, 1.241 [1-sided p = 0.894]). Secondary efficacy outcomes were broadly consistent with the 2-year LDCR results. In both doses, gefitinib was well-tolerated and did not adversely affect the safety and tolerability of concomitant chemoradiotherapy.

Conclusion

Gefitinib was well-tolerated, but did not improve efficacy compared with placebo when given concomitantly with chemoradiotherapy, or as maintenance therapy alone.     

The impact of postmastectomy radiotherapy on local control in patients with invasive lobular breast cancer

Purpose

The aim of this population-based study was to examine the impact of postmastectomy radiotherapy on the risk of local recurrence in patients with invasive lobular breast cancer (ILC).

Methods

The population-based Eindhoven Cancer Registry was used to select all patients with ILC, who underwent mastectomy in five general hospitals in the southern part of the Netherlands between 1995 and 2002. Of the 499 patients 383 patients fulfilled the eligibility criteria. Of these patients, 170 (44.4%) had received postmastectomy radiotherapy. The median follow-up was 7.2 years. Fourteen patients (3.7%) were lost to follow-up.

Results

During follow-up 22 patients developed a local recurrence, of whom 4 had received postmastectomy radiotherapy. The 5-year actuarial risk of local recurrence was 2.1% for the patients with and 8.7% for the patients without postmastectomy radiotherapy. After adjustment for age at diagnosis, tumour stage and adjuvant systemic treatment, the patients who underwent postmastectomy radiotherapy were found to have a more than 3 times lower risk of local recurrence compared to the patients without (Hazard Ratio 0.30; 95% Confidence Interval: 0.10-0.89).

Conclusion

Local control is excellent for patients with ILC who undergo postmastectomy radiotherapy and significantly better than for patients not receiving radiotherapy.     

Higher serum C-reactive protein concentration and hypoalbuminemia are poor prognostic indicators in patients with esophageal cancer undergoing radiotherapy

Background and purpose

We evaluate if C-reactive protein (CRP) is an objective biomarker of esophageal cancer in patients undergoing radiotherapy.

Materials and methods

Between November 2002 and July 2007, 123 patients undergoing radiotherapy for newly diagnosed esophageal cancer were enrolled. Serum CRP concentration was measured before the initiation of treatment. The relationship between serum CRP levels and other relevant variables such as body mass index, white blood cell count, platelet count, bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), cholesterol, hemoglobin, and albumin levels was also analyzed.

Results

Eighty-one patients of the 123 patients enrolled (65.9%) had elevated CRP levels (?5 mg/L). The 2-year survival for patients with CRP ?5 mg/L was 7.8% compared to 78.4% for patients with CRP <5 mg/L. Hypoalbuminemia (albumin <3.5 g/dL) was also related to shorter survival using univariate analysis. Multivariate analysis demonstrated that only higher serum CRP concentration and hypoalbuminemia were independent prognostic indicators for survival of patients with esophageal cancer.

Conclusions

Pretreatment serum levels of CRP and albumin are objective, easily measurable biomarkers which can be used in combination with conventional staging to accurately predict survival in patients with esophageal cancer treated with radiotherapy.     

The influence of the use of CT-planning on the irradiated boost volume in breast conserving treatment

Background and purpose

The purpose of this study was to investigate the effect of CT-based delineation and planning on the irradiated boost volume. For this specific purpose we used the data as derived from 2 prospective phase III randomised trials.

Patients and methods

Data from 1331 patients (?50 years) were analyzed with a reported boost volume from a simulation-based treatment plan (EORTC boost vs no boost trial, n = 922), and a CT-scan-based treatment plan (Young Boost Trial, n = 409) group. Tumour diameter, irradiation technique (photons vs electrons), lumpectomy size, and age were used as covariates.

Results

Median V_95% in the conventional simulation-based treatment plans was 99 cc (range 9-628) for photons and was 98 cc (13-651) for electrons, whereas in the CT-planned patients, these figures were 178 cc (37-2699) and 150 cc (43-1272), respectively. Multivariable analysis showed an association of the irradiated boost volume with tumour size (p < 0.0067), lumpectomy size (p < 0.0002), and boost technique (p < 0.0004). The use of a CT-scan for volume delineation and treatment planning remained significant (p < 0.0001).

Conclusions

The use of a CT-scan for delineation and treatment planning led to a significant increase of the irradiated boost volume by a factor of 1.5-1.8, compared to conventional simulator-based plans.     

Definitive chemoradiation for oesophageal cancer--a standard of care in patients with non-metastatic oesophageal cancer

Aims

A retrospective analysis was carried out of 291 cases of oesophageal cancer treated with definitive chemoradiotherapy (dCRT) at a single UK cancer centre between 1995 and 2009. Our protocol consisted of two cycles of neoadjuvant platinum-based chemotherapy followed by two further cycles given concurrently with 50 Gy of external beam radiotherapy delivered in 25 fractions over 5 weeks.

Materials and methods

Demographic, patient and outcome data were recorded prospectively through an electronic health record and retrospectively analysed, using appropriate statistical tools.

Results

Data on 266 patients were available for analysis. The median age was 66.6 years, 53% were adenocarcinomas. dCRT was used instead of surgery because of age/co-morbidity in 44% and disease extent in 39%. Ninety-three per cent of patients completed treatment according to protocol. Grade 3 and 4 toxicities were seen in 42 and 7%, respectively. Median survival was 20.6 months; 2, 3 and 5 year survival rates were 43.6, 32.9 and 19.5%, respectively. Advanced disease was associated with a worse outcome. Shorter disease length was associated with a better median survival, but some patients with disease >10 cm had long-term disease control. The effect of other patient- and disease-related factors was also analysed.

Conclusion

We present data showing that dCRT is well tolerated and should be considered as an alternative to surgery for all patients with locally advanced oesophageal cancer, not only those with co-morbidity. Furthermore, the benefits of dCRT are not confined to carcinomas with squamous histology.     

A phase II study of neoadjuvant chemoradiotherapy with oxaliplatin and capecitabine for rectal cancer

Purpose

This study evaluated the efficacy and safety of neoadjuvant chemoradiotherapy with the XELOX regimen in rectal cancer patients.

Patients and methods

Twenty-five patients with histopathologically confirmed and locally advanced rectal cancer (T3/T4 or N+) were enrolled in the study. Radiotherapy of 5000 cGy was delivered in 25 fractions of 200 cGy five times per week for a total of 5 weeks. During the first, second, fourth and fifth weeks of radiotherapy, the patients also received the following chemotherapy: 50 mg/m² oxaliplatin on day one and 850 mg/m² capecitabine bid for 5 days. Surgery was scheduled 5–6 weeks after the completion of the preoperative chemoradiotherapy. Four weeks after the surgery, four more cycles of chemotherapy were administered every 3 weeks. The postoperative chemotherapy consisted of 130 mg/m² oxaliplatin on day 1 and 1000 mg/m² capecitabine bid from day 1 to day 14. The end points were the downstage rate, R0 resection rate, and sphincter preservation rate.

Results

Twenty-five patients received the neoadjuvant chemoradiotherapy. The overall regression rate was 85%, with a Grade 3/4 regression rate of 30% and a pathological complete response rate of 12%. Among the 17 patients with lower rectal cancer, thirteen (76%) were originally indicated for abdominal–perineal resection (APR). However, after the neoadjuvant chemoradiotherapy, the anus could be preserved in nine patients (53%). The most frequent toxicities of the chemoradiotherapy were diarrhea (64%) and hematological toxicity (60%), followed by nausea and vomiting (48%), urinary tract irritation (28%), and anal pain (24%). Grade 3 or 4 adverse events were relatively infrequent and presented as diarrhea (12%), myelosuppression (8%), and elevated transaminase (4%). Six cases also experienced long-term anal exudates after surgery.

Conclusions

Neoadjuvant chemoradiotherapy using the XELOX regimen in rectal cancer patients obviously reduced the TNM staging and improved the pathological complete response rate. The therapy was well-tolerated and had mild adverse events and no serious perioperational complications.     

Accuracy requirements for head and neck intensity-modulated radiation therapy based on observed dose response of the major salivary glands

Background and Purpose

We estimated accuracy requirements for dose and position of the major salivary glands in head and neck intensity-modulated radiotherapy (IMRT) based on the dose response characteristics of the glands obtained by using the sigmoidal dose response model.

Materials and methods

Dose response of the parotid and submandibular salivary glands was determined for 25 head and neck cancer patients treated by IMRT. Individual salivary gland functions were assessed by scintigraphy before and 6 months after radiotherapy. Accuracy requirements were estimated by using the maximal slope of the fitted dose response model and average value of the dose gradients within the glands. In addition, systematic and random set-up errors were estimated for each patient by at least weekly portal imaging. We investigated the changes in the salivary gland mean doses (D_mean) that would have occurred without correction of patient positioning. This was done by shifting the planned isocenter according to the obtained systematic set-up error and by recalculating the dose distribution in treatment planning system (TPS).

Results

The maximal slope and D₅₀ values of the dose response model were −0.041 1/Gy and 30.4 Gy, respectively. The results suggested that spared fraction of individual salivary gland function can be estimated with an accuracy of ±10%, if actual D_mean of the gland is within ±2.4 Gy with the planned value. On the average, this was achieved with maximal systematic positional 3D shift of 3.0 mm for the parotid glands and 2.7 mm for the submandibular glands. The magnitude of systematic 1D set-up errors was 1.7 ± 1.3 mm (mean ± SD) while that of systematic 3D errors was 3.4 ± 1.6 mm. The SD of random set-up errors was 1.5 mm. The magnitude of D_mean shifts due to set-up errors was 1.5 ± 1.4 Gy. The steepness of dose gradients within the glands was 0.8 ± 0.5 Gy/mm in the most critical direction (toward the glands).

Conclusions

When substantial part of salivary gland function is intended to be spared in head and neck IMRT, narrow dosimetric and positional tolerances should be adopted for the major salivary glands due to steep dose response curve obtained for the glands.     

Linac-based isocentric electron–photon treatment of radically operated breast carcinoma with enhanced dose uniformity in the field gap area

Background and purpose

Isocentric treatment technique is a standard method in photon radiotherapy with the primary advantage of requiring only a single patient set-up procedure for multiple fields. However, in electron treatments the size of the standard applicators does not generally allow to use an isocentric treatment technique. In this work we have modified and dosimetrically tested electron applicators for isocentric treatments in combination with photons. An isocentric treatment technique with photons and electrons for postmastectomy radiation therapy (PMRT) has been developed with special emphasis on improving the dose uniformity in the field gap area.

Materials and methods

Standard electron applicators of two Varian Clinac 2100CD linear accelerators were shortened by 10 cm allowing isocentric treatments of 90 cm < SSD < 100 cm in electron fields. Shortened applicators were commissioned and configured for the electron calculation algorithm of the treatment planning system. The field arrangement of PMRT was modified by combining three photon field segments with different gaps and overlaps with the electron field to improve dose uniformity. The developed technique and two other methods for PMRT were compared with each other in the group of 20 patients.

Results

Depth dose characteristics of the shortened applicators remained unchanged from those of the standard applicators. Penumbrae were broadened by 0-3 mm depending on electron energy and depth as the air gap was increased from 5 cm (standard applicator at SSD = 100 cm) to 10 cm (shortened applicator at SSD = 95 cm). The dose calculation performance of the modified applicators at 95 cm < SSD < 100 cm was considered similar as with standard applicators at SSD = 100 cm using the Gaussian pencil beam electron dose calculation algorithm of the treatment planning system (Varian Eclipse). The modified isocentric treatment technique for PMRT was superior than the traditional two-dimensional technique. However, with the tangential photon fields without electrons the even better dose uniformity within PTV could be achieved but with increased irradiation of healthy tissues (lung, heart, and contralateral breast). The modified isocentric technique was also found faster than the traditional technique with SSD = 100 cm fields.

Conclusions

It is possible to apply an isocentric treatment technique in PMRT with electrons and photons. The homogeneity of the dose distribution can be improved by adding more photon field segments. With the isocentric technique it is possible to achieve even some time sparing in treatment delivery compared with the traditional SSD = 100 cm technique.     

Continuous EGFR-TKI administration following radiotherapy for non-small cell lung cancer patients with isolated CNS failure

Introduction

Based on previous reports, patients who experience isolated central nervous system (CNS) failure may not have systemic acquired resistance to EGFR-TKI therapy. However, because there are few articles that have reported on the clinical efficacy of continuous EGFR-TKI administration following progressive disease (PD) in isolated CNS metastasis, we retrospectively investigated the possibility of using the treatment.

Patients and methods

From July 2002 to December 2009, 17 non-small cell lung cancer patients showed isolated CNS failure after clinical benefit (partial response or stable disease longer than 6 months) from EGFR-TKIs and continuously received EGFR-TKIs following radiotherapy (whole brain radiotherapy or stereotactic radiotherapy) to the CNS metastases.

Results

The response rate and the disease control rate of CNS lesions were 41% and 76%, respectively. The median progression free survival, extracranial progression free survival and the median overall survival time were 80 days, 171 days and 403 days, respectively. The toxicities which were observed during the first EGFR-TKI treatments were sustained, but did not worsen during this study period. The acute toxicities caused by radiotherapy to the CNS were controllable. There were no remarkable late toxicities related to the treatment.

Conclusions

Continuous administration of EGFR-TKI following radiotherapy after PD in isolated CNS metastasis appears to be a valid treatment option.     

Pathologic response rates following definitive dose image-guided chemoradiotherapy and resection for locally advanced non-small cell lung cancer

Introduction

Treatment of technically operable, medically fit locoregionally advanced non-small cell lung cancer (NSCLC) patients is a controversial therapeutic challenge. Our group routinely uses a trimodality approach. Recent advances in radiotherapy allow for improved tumor targeting and daily patient positioning. We hypothesized that these technologies would improve pathologic response rates. We analyzed consecutively treated stage IIIA/IIIB NSCLC patients undergoing chemoradiotherapy before major lung resection, with particular attention paid to the impact of advanced technologies.

Methods

Locoregionally advanced NSCLC patients (N2) staged in a multidisciplinary forum with mediastinoscopy were planned to receive platinum-based chemotherapy and 60 Gy and major lung resection. Four-dimensional CT (4DCT) and image-guided radiotherapy (IGRT) were used as available. Survival endpoints were estimated using the Kaplan-Meier method and compared using the log-rank test. Multivariate analysis was performed using Cox proportional hazards models.

Results

We identified 53 patients from 2/1999 to 2/2010. Median RT dose was 59 Gy. 68% underwent lobectomy. Forty-three patients were downstaged pathologically (81%), 38 experienced mediastinal sterilization (72%), and 21 (40%) had complete pathologic response (pCR). 1 and 2 year OS were 85.5% and 61.6%. Superior OS and DFS were associated with nodal downstaging and mediastinal sterilization (pN0). Treatment with IGRT/4DCT in 10 patients resulted in high rates of nodal downstaging (100% vs 77%, p = 0.0452), mediastinal sterilization (90% vs 67%, p = 0.0769), and pCR (60% vs 35%, p = 0.0728).

Conclusions

In selected patients, definitive dose CRT followed by major lung resection results in promising DFS and OS. The use of advanced radiotherapy techniques (4DCT and IGRT) appears to result in promising pathologic response rates.