The use of palliative radiotherapy for bone metastasis

Background

The value of palliative radiotherapy (PRT) for bone metastases is well established, but little is known about its use in the general population.

Purpose

To describe the use of PRT for bone metastases in Ontario.

Materials and methods

This was a retrospective cohort study. Treatment records from all Ontario RT departments were linked to a population-based cancer registry to describe the use of PRT.

Results

12.2% of the 434,241 patients, who died of cancer in Ontario between 1984 and 2004, received at least one course of PRT for bone metastases in the last 2 years of life. The rate of use of PRT varied across the province (inter-county range, 8.2-18.6%). Older patients and residents of poorer areas were less likely to receive PRT (p < 0.0001). Patients diagnosed with cancer in a hospital with a radiotherapy facility and those who lived closer to a radiotherapy centre were more likely to receive PRT (p < 0.0001). Over the study period, the use of PRT decreased in breast cancer and myeloma, but increased in prostate cancer (p < 0.0001).

Conclusions

Access to PRT appears to be inequitable. More effort is required to make this useful treatment available to all those who would benefit from it.     

Disparities in lung cancer stage, treatment and survival among American Indians and Alaskan Natives

Background

Disparities in lung cancer care and outcomes have been documented for blacks and Hispanics. Less is known about the care received by the American Indian and Alaskan Native population (AI/AN). We sought to evaluate lung cancer outcomes in this population and to asses if potential disparities in survival are explained by differences in stage of disease at diagnosis and type of treatment received.

Methods

We identified patients with potentially resectable (stages I-IIIA) non-small cell lung cancer (NSCLC) from the Surveillance, Epidemiology and End Results registry between 1988 and 2006. Kaplan-Meier curves were used to compare survival of AI/AN patients to those of other racial groups. Cox regression analysis was used to identify potential mediators of the association between AI/AN origin and worse survival.

Results

Five-year lung cancer survival was 47% for AI/AN, 56% for whites, 51% for blacks, 55% for Hispanics and 59% for individuals of other race (p < 0.0001). AI/AN were more likely to be diagnosed with stage IIIA (p < 0.0001) and less likely to undergo resection (p < 0.0001) than whites. In multivariable regression analyses, controlling for patient characteristics and histology, AI/AN race was associated with worse survival than white patients. When stage, treatment and surgery were added to the model, AI/AN origin was no longer significantly associated with worse outcomes.

Conclusions

AI/AN with potentially resectable NSCLC have survival rates comparable to other minority groups and worse than whites. These survival differences are partly explained by advanced stage at diagnosis, and lower rates of treatment.     

Symptoms 10-17 years after breast cancer radiotherapy data from the randomised SWEBCG91-RT trial

Background

Postoperative radiotherapy decreases the risk for local recurrence and improves overall survival in women with breast cancer. We have limited information on radiotherapy-induced symptoms 10-17 years after therapy.

Material and methods

Between 1991 and 1997, women with lymph node-negative breast cancer were randomised in a Swedish multi-institutional trial to breast conserving surgery with or without postoperative radiotherapy. In 2007, 10-17 years after randomisation, the group included 422 recurrence-free women. We collected data with a study-specific questionnaire on eight pre-selected symptom groups.

Results

For six symptom groups (oedema in breast or arm, erysipelas, heart symptoms, lung symptoms, rib fractures, and decreased shoulder mobility) we found similar occurrence in both groups. Excess occurrence after radiotherapy was observed for pain in the breast or in the skin, reported to occur “occasionally” by 38.1% of survivors having undergone radiotherapy and surgery versus 24.0% of those with surgery alone (absolute difference 14.1%; p = 0.004) and at least once a week by 10.3% of the radiotherapy group versus 1.7% (absolute difference 8.6%; p = 0.001). Daily life and analgesic use did not differ between the groups.

Conclusions

Ten to 17 years after postoperative radiotherapy 1 in 12 women had weekly pain that could be attributed to radiotherapy. The symptoms did not significantly affect daily life and thus the reduced risk for local recurrence seems to outweigh the risk for long-term symptoms for most women.     

The number of axillary nodes removed as a predictor of regional recurrence in node negative breast cancer

Purpose

To determine if the number of axillary nodes removed is a predictor of recurrence in node negative breast cancer.

Materials and methods

Five hundred thirty-six patients with T1-T2, N0 invasive breast cancer, treated with lumpectomy and axillary node dissection (AND), were reviewed from January 1, 1986 to December 31, 1992. Patients received radiation to whole breast only, without regional nodal radiation. There was no adjuvant chemotherapy or Tamoxifen given. Patients were grouped according to the number of axillary nodes dissected as follows: 1-5 nodes (91 patients), 6-10 nodes (225 patients) and >10 nodes (220 patients). Hazard ratios and p-values were determined for time to local recurrence, regional recurrence and for disease specific survival.

Results

Median follow-up was 11.2 years. The overall local recurrence and regional recurrence rates for the three groups were: 1-5 nodes, 9.9% and 8.8%, respectively, 6-10 nodes, 10.2% and 2.2%, respectively, and >10 nodes, 11.8% and 2.7%, respectively. The effect of number of axillary nodes removed was statistically significant only for regional recurrence (p = 0.017). There was no adverse effect on disease specific survival (p = 0.363).

Conclusion

The number of axillary nodes removed predicts only for regional recurrence in node negative breast cancer patients, with less than 6 nodes removed associated with higher regional recurrence. This may have clinical implications with the current practice of sentinel node biopsy (SNB) replacing axillary node dissection in early stage breast cancer.     

Meta-analysis of predictive factors for non-sentinel lymph node metastases in breast cancer patients with a positive SLN

Aims

A meta-analysis was performed to identify the clinicopathological variables most predictive of non-sentinel node (NSN) metastases when the sentinel node is positive.

Methods

A Medline search was conducted that ultimately identified 56 candidate studies. Original data were abstracted from each study and used to calculate odds ratios. The random-effects model was used to combine odds ratios to determine the strength of the associations.

Findings

The 8 individual characteristics found to be significantly associated with the highest likelihood (odds ratio >2) of NSN metastases are SLN metastases >2 mm in size, extracapsular extension in the SLN, >1 positive SLN, ≤1 negative SLN, tumour size >2 cm, ratio of positive sentinel nodes >50% and lymphovascular invasion in the primary tumour. The histological method of detection, which is associated with the size of metastases, had a correspondingly high odds ratio.

Conclusions

We identified 8 factors predictive of NSN metastases that should be recorded and evaluated routinely in SLN databases. These factors should be included in a predictive model that is generally applicable among different populations.     

Socioeconomic inequalities in the use of radiotherapy for rectal cancer: A nationwide study

Preoperative radiotherapy (PRT) in rectal cancer reduces the risk of local recurrence by at least half but the influence of the socioeconomic status of patients on the use of PRT is little investigated in Europe.

Methods

Individually attained data on civil status, education and income were linked to the Swedish Rectal Cancer Registry 1995-2005 (n = 16,713) and analysed by logistic regression.

Results

Forty-six percentage of the patients received PRT and the crude rate varied with age, gender, civil status, education and income as well as with sublocalisation, stage, type of hospital and health care region. In a multivariate analysis, all civil status groups had PRT to a lesser extent compared with married patients; odds ratio (OR) for unmarried patients was 0.67 (95% confidence interval (CI) 0.59-0.76). Patients with secondary and university education had PRT to the same extent as those with compulsory school (OR 1.04 (0.94-1.15) and 0.92 (0.81-1.06)). The use of PRT was associated with income; OR for patients with income Q1 versus Q4 was 0.76 (0.67-0.86). The inequalities by civil status and income remained unchanged also in groups with a relatively stronger indication for adjuvant radiotherapy, i.e. younger patients and in low rectal cancer.

Conclusion

Unmarried and low-income patients are at increased risk for not receiving PRT in rectal cancer. Comorbidity may explain some differences but increased awareness of the role of non-medical variables for the use of PRT is warranted.     

Phase I study of concurrent real-time tumor-tracking thoracic radiation therapy with paclitaxel and carboplatin in locally advanced non-small cell lung cancer

Introduction

Although paclitaxel with carboplatin and thoracic radiotherapy has improved survival for patients with locally advanced unresectable non-small cell lung cancer (NSCLC), the optimal dose of paclitaxel has not been well defined in Japan. This study was conducted to determine the maximum tolerated dose (MTD) and recommended dose (RD) of paclitaxel in combination with carboplatin and concurrent real-time tumor-tracking thoracic radiation therapy (thoracic RTRT).

Patients and methods

Previously untreated patients with histologically confirmed, locally advanced unresectable NSCLC were eligible. Before treatment, gold markers were inserted into the lung and the mediastinum of all patients. RTRT comprised a total of 66 Gy at 2 Gy/fraction, 5 days/week, for 7 weeks. Patients received paclitaxel at a starting dose of 40 mg/m² followed by carboplatin at a fixed area under the curve (AUC) of 2, as a weekly regimen with RTRT. The dose of paclitaxel was escalated by 5 mg/m² per level.

Results

Eight patients with locally advanced unresectable NSCLC were enrolled and treated with two dose levels of paclitaxel (40 mg/m² and 45 mg/m²), carboplatin (AUC = 2) and RTRT. No dose limiting toxicities (DLTs) were observed at Level 1 (paclitaxel, 40 mg/m² and carboplatin, AUC = 2). At Level 2 (paclitaxel, 45 mg/m² and carboplatin, AUC = 2), two of five patients experienced DLTs, in the form of esophagitis and discontinuation of chemotherapy more than twice. The MTD and RD of paclitaxel were thus defined as 45 mg/m² and 40 mg/m², respectively.

Conclusions

This phase I study was well tolerated and the RD of paclitaxel and carboplatin with RTRT is 40 mg/m² at AUC = 2, respectively. Further studies are warranted to evaluate the efficacy of this regimen.     

Prognostic impact of comorbidity in elderly lung cancer patients: Use and comparison of two scores

Background

Mean age of patients with lung cancer rises as a result of increasing life expectancy. So, the proportion of patients with serious comorbidity also increases [1] and [2]. Lung cancer treatment is characterized by a narrow therapeutic index. When life expectancy is short and therapeutic benefit is limited, it is of paramount importance to know the specific cause of death. Comorbidity is understood as a competing cause of death, and is the main exclusion criterion for lung cancer clinical trials. The aim of this study was to determine the prevalence of comorbidity in elderly lung cancer patients seen in an outpatient oncology department and to determine its correlation with survival.

Patients and methods

Between January 2006 and February 2008, 83 untreated lung cancer patients over the age of 70 years were enrolled in the study. Comorbidity was evaluated according to the Charlson comorbidity index (CCI) [3] and the simplified comorbidity score (SCS) [4].

Results

83 patients (97.6% men, mean age 77 years) were studied. Comorbidities: tobacco consumption (94.6%), cardiovascular diseases (65%), and chronic obstructive pulmonary disease (COPD) (59%). Mean CCI was 3 (range 0-9). Mean SCS was 9 (range 4-19), and 47% of patients had an SCS > 9. Comorbidity was fairly well correlated with age, ADL, IADL, and stage. Neither the CCI nor the SCS was related to survival (p: 0.47 and p: 0.24, log rank, respectively). Median survival was 326 days (95% CI, 259-393 days; or 10.8 months, 95% CI 8.6-13.1 months). Main cause of death was lung cancer disease progression (69.5%, 57 patients), with 20 patients (25%) dying of other non-neoplastic causes. Stage was significantly associated with survival (log rank: p < 0.001).

Conclusions

Although there was a high prevalence of comorbidity in our population, comorbidity was not related to survival. Comorbidity is one of the main reasons for undertreatment of elderly lung cancer patients, but this study indicates that this undertreatment may not be warranted given that those comorbidities may not cause a patient's death. Our data generated more of a hypothesis than a conclusion. Comorbidity should be an impetus for treatment design instead of an exclusion criterion for oncologic treatment.     

Impact of radiation dose on locoregional control and survival on squamous cell carcinoma of anal canal

Purpose

To perform a systematic analysis of clinical data of presentation, treatment, outcome, toxicity, survival and other associated prognostic factors of the patients of anal canal who received treatment at our hospital.

Methods and materials

The medical records of 257 patients treated with radiotherapy with or without chemotherapy from the year 1985 to 2005 were studied.

Results

Median follow-up was 36 months. Complete clinical response after radiotherapy was 74.4% in the whole group. The 5 years overall (OAS) and disease-free (DFS) survival for the whole group was 71.5% and 61%, respectively. Patients with T1-2 tumors which received the radiation dose between 55 and 60 Gy had superior locoregional control, DFS and OAS. Similarly T3-4 tumors receiving radiation dose more than 60 Gy independently improved the locoregional control, DFS and OAS irrespective of the nodal status and addition of chemotherapy.

Conclusions

Radiation dose of 56-60 Gy for T1 and T2 and 65 Gy for T3 and T4 tumors along with concurrent chemotherapy is required to achieve better local control, disease-free survival and overall survival, with acceptable toxicity.     

Comparison of efficacy and toxicity of short-course carbon ion radiotherapy for hepatocellular carcinoma depending on their proximity to the porta hepatis

Background and purpose

To compare the efficacy and toxicity of short-course carbon ion radiotherapy (C-ion RT) for patients with hepatocellular carcinoma (HCC) in terms of tumor location: adjacent to the porta hepatis or not.

Materials and methods

The study consisted of 64 patients undergoing C-ion RT of 52.8 GyE in four fractions between April 2000 and March 2003. Of these patients, 18 had HCC located within 2 cm of the main portal vein (porta hepatis group) and 46 patients had HCC far from the porta hepatis (non-porta hepatis group). We compared local control, survival, and adverse events between the two groups.

Results

The 5-year overall survival and local control rates were 22.2% and 87.8% in the porta hepatis group and 34.8% and 95.7% in the non-porta hepatis group, respectively. There were no significant differences (P = 0.252, P = 0.306, respectively). Further, there were no significant differences in toxicities. Biliary stricture associated with C-ion RT did not occur.

Conclusions

Excellent local control was obtained independent of tumor location. The short-course C-ion RT of 52.8 GyE in four fractions appears to be an effective and safe treatment modality in the porta hepatis group just as in the non-porta hepatis group.     

Chemoreirradiation for recurrent salivary gland malignancies

Background and purpose

To report our experience in treating recurrent salivary gland malignancies using concurrent chemotherapy and reirradiation.

Materials and methods

Between 1986 and 2007, 14 patients with locoregionally recurrent salivary gland cancer underwent maximal surgical resection followed by adjuvant 5-fluorouracil and hydroxyurea-based chemotherapy concurrently with 1.5 Gy twice daily or 2 Gy daily reirradiation. Each cycle consisted of chemoreirradiation for 5 consecutive days followed by a 9-day break. The median reirradiation dose was 66 Gy (R 30-72 Gy) after a mean radiation treatment interval of 48 months.

Results

The median follow-up for all patients was 18 months (R 2-125 months) and 41 months for survivors. The parotid gland (n = 6) and minor salivary glands (n = 6) were involved more commonly than the submandibular gland (n = 2). Locoregional control at 1 and 3 years was 72.2% and 51.6%, respectively. Actuarial overall survival at 3 and 5 years was 35.7% and 26.8%, respectively. Tracheostomies and feeding tubes were placed in 2 and 8 patients, respectively. Six patients had feeding tubes at last follow-up or death.

Conclusions

Concurrent chemotherapy and reirradiation for recurrent salivary malignancies result in promising locoregional control for patients with recurrent salivary gland malignancies.     

Duration of prior gefitinib treatment predicts survival potential in patients with lung adenocarcinoma receiving subsequent erlotinib

Purpose

We investigated survival potential in patients receiving erlotinib after failure of gefitinib, focusing on response and time to progression (TTP) with gefitinib.

Methods

We retrospectively reviewed lung adenocarcinoma patients who received erlotinib after experiencing progression with gefitinib. Our primary objective was to evaluate the prognostic significance of erlotinib therapy.

Results

A total 42 lung adenocarcinoma patients were included in this study. Overall disease control rate was 59.5% (partial response [PR], 2.4%; stable disease [SD], 57.1%). Median overall survival was 7.1 months, and median progression-free survival was 3.4 months. The number of patients who achieved PR and non-PR (SD+ progressive disease [PD]) with gefitinib were 22 (52%) and 20 (48%), respectively. Patients with PR for gefitinib showed significantly longer survival times than those with non-PR (9.2 vs. 4.7 months; p = 0.014). In particular, among PR patients, those with TTP <12 months on gefitinib showed significantly longer survival times than those with TTP ≥12 months (10.3 vs. 6.4 months; p = 0.04).

Conclusions

Erlotinib may exert survival benefit for lung adenocarcinoma patients with less than 12 months of TTP of prior gefitinib who achieved PR for gefitinib.     

Treatment outcomes for patients with synchronous multiple primary non-small cell lung cancer

Introduction

The development of synchronous multiple primary non-small cell lung cancer (NSCLC) is not rare. Nevertheless, the diagnosis, treatment and outcome are controversial. The purposes of this study were to assess the treatment outcomes for patients with synchronous multiple primary NSCLC and to analyze the factors related to this outcome.

Methods

We retrospectively analyzed clinical characteristics and treatment outcomes of 32 patients with synchronous multiple primary NSCLC who underwent surgical resection between 1995 and 2008.

Results

A total of 68 separate tumors were identified in 32 patients. Fifteen (46.9%) patients underwent lobectomy or pneumonectomy with mediastinal lymph node dissection, and 17 (53.1%) patients underwent at least one limited resection or photodynamic therapy. The rate of immediate postoperative mortality was 9.4% (N = 3). The five-year progression-free survival (PFS) and overall survival (OS) rates were 46.0% and 60.9%, respectively. Small tumor size, similar histology, pN0, and pT1 were associated with better PFS in univariable analyses. Female gender, young age, non-smoker, FEV1/FVC ≥70%, small tumor size, similar histology, and highest pT1 were associated with better OS in univariable analyses.

Conclusions

An aggressive surgical approach offers the greatest chance for long-term survival in patient with synchronous multiple primary NSCLC and several clinical factors were associated with survivals. However, the decision of aggressive surgical treatments for synchronous MPLC should be made carefully in the patients with old age and underlying comorbidities due to poor OS and increased surgical mortality.     

Curative chemoradiotherapy for isolated retroperitoneal lymph node recurrence of colorectal cancer

Purpose

To investigate the efficacy of curative chemoradiotherapy for isolated retroperitoneal lymph node recurrence of colorectal cancer.

Materials and methods

Twenty-two colorectal cancer patients who received three-dimensional conformal radiotherapy (n = 20) or helical tomotherapy (n = 2) for isolated retroperitoneal lymph node recurrence were analyzed retrospectively. Radiation dose was 55.8 Gy in 31 fractions or 63 Gy in 35 fractions, and 60 Gy in 20 fractions by helical tomotherapy. All patients received concurrent chemotherapy and 16 (72.7%) received adjuvant chemotherapy.

Results

The treatment response was complete in 13 (59.1%), partial in 6 (27.3%), and stable in 3 (13.6%) patients. Median follow-up for 11 (50%) surviving patients was 32 months (range, 27-61). The 3- and 5-year overall survival rates were 64.7% and 36.4%, and median overall survival was 41 months. Recurrences developed in 15 (68.2%) patients; outside the retroperitoneum in 13. The 3- and 5-year recurrence-free survival rates were 34.1% and 25.6%, and median recurrence-free survival was 20 months. Response and adjuvant chemotherapy were significant prognostic factors for overall survival. Gastrointestinal toxicity ? Grade 3 was not observed.

Conclusions

Definitive chemoradiotherapy is an effective salvage treatment for isolated retroperitoneal lymph node recurrence of colorectal cancer without severe complications.     

Applicator reconstruction in MRI 3D image-based dose planning of brachytherapy for cervical cancer

Background and purpose

To elaborate a method for applicator reconstruction for MRI-based brachytherapy for cervical cancer.

Materials and methods

Custom-made plastic catheters with a copper sulphate solution were made for insertion in the source channels of MR-CT compatible applicators: plastic and titanium tandem ring applicators, and titanium needles. The applicators were CT and MR scanned in a phantom for accurate 3D assessment of applicator visibility and geometry. A reconstruction method was developed and evaluated in 19 patient MR examinations with ring applicator (plastic: 14, titanium: 5). MR applicator reconstruction uncertainties related to inter-observer variation were evaluated.

Results

The catheters were visible in the plastic applicator on T1-weighted images in phantom and in 14/14 clinical applications. On T2-weighted images, the catheters appeared weaker but still visible in phantom and in 13/14 MR clinical applications. In the titanium applicator, the catheters could not be separated from the artifacts from the applicator itself. However, these artifacts could be used to localize both titanium ring applicator (5/5 clinical applications) and needles (6/6 clinical applications). Standard deviations of inter-observer differences were below 2 mm in all directions.

Conclusion

3D applicator reconstruction based on MR imaging could be performed for plastic and titanium applicators. Plastic applicators proved well to be suited for MRI-based reconstruction. For improved practicability of titanium applicator reconstruction, development of MR applicator markers is essential. Reconstruction of titanium applicator and needles at 1.5 T MR requires geometric evaluations in phantoms before using the applicator in patients.     

Angiotensin system inhibitors and outcome of sunitinib treatment in patients with metastatic renal cell carcinoma: a retrospective examination

Background

Sunitinib is a standard treatment for metastatic renal cell carcinoma. Angiotensin system inhibitors, including angiotensin converting enzyme inhibitors and angiotensin II receptor blockers, are widely used in hypertension, kidney disease and heart failure. Data suggests that they may inhibit tumourigenesis.

Aims

To study the effect of angiotensin system inhibitors on sunitinib treatment outcome in metastatic renal cell carcinoma.

Methods

We performed a retrospective study of an unselected cohort of patients with metastatic renal cell carcinoma who were treated with sunitinib. Patients were divided into angiotensin system inhibitors users (group 1) and non-users (group 2). The effect of angiotensin system inhibitors on objective response, time to disease progression and overall survival, was tested with adjustment for known confounding risk factors through logistic regression model and Cox regression model.

Results

Between 2004 and 2010, 127 patients with metastatic renal cell carcinoma were treated with sunitinib, 44 group 1 and 83 group 2. The groups were balanced regarding known clinicopathologic prognostic factors. Objective response was partial response/stable disease 86% versus 72% and progressive disease 14% versus 28% (p = 0.07) in group 1 versus 2, respectively. Median progression free survival was 13 versus 6 months (HR 0.537, p = 0.0055), and median overall survival 30 versus 23 months (HR 0.688, p = 0.21), in favour of group 1.

Conclusions

Angiotensin system inhibitors may improve the outcome of sunitinib treatment in metastatic renal cell carcinoma. This should be investigated prospectively, and if validated applied in clinical practise and clinical trials.     

Overexpression of the mammalian target of rapamycin (mTOR) and angioinvasion are poor prognostic factors in early stage NSCLC: a verification study

Background

A recent study by Dhillon et al. [12], identified both angioinvasion and mTOR as prognostic biomarkers for poor survival in early stage NSCLC. The aim of this study was to verify the above study by examining the angioinvasion and mTOR expression profile in a cohort of early stage NSCLC patients and correlate the results to patient clinico-pathological data and survival.

Methods

Angioinvasion was routinely recorded by the pathologist at the initial assessment of the tumor following resection. mTOR was evaluated in 141 early stage (IA-IIB) NSCLC patients (67 - squamous; 60 - adenocarcinoma; 14 - others) using immunohistochemistry (IHC) analysis with an immunohistochemical score (IHS) calculated (% positive cells × staining intensity). Intensity was scored as follows: 0 (negative); 1+ (weak); 2+ (moderate); 3+ (strong). The range of scores was 0-300. Based on the previous study a cut-off score of 30 was used to define positive versus negative patients. The impact of angioinvasion and mTOR expression on prognosis was then evaluated.

Results

101 of the 141 tumors studied expressed mTOR. There was no difference in mTOR expression between squamous cell carcinoma and adenocarcinoma. Angioinvasion (p = 0.024) and mTOR staining (p = 0.048) were significant univariate predictors of poor survival. Both remained significant after multivariate analysis (p = 0.037 and p = 0.020, respectively).

Conclusions

Our findings verify angioinvasion and mTOR expression as new biomarkers for poor outcome in patients with early stage NSCLC. mTOR expressing patients may benefit from novel therapies targeting the mTOR survival pathway.     

HDR endobronchial brachytherapy (HDRBT) in the management of advanced lung cancer - Comparison of two different dose schedules

Purpose

The aim of this work is to compare the results of various treatment protocols used in palliative HDRBT with the view of analyzing differences in survival and diminishing breathing difficulties.

Material and methods

A total of 648 patients with advanced lung cancer were divided into two groups according to their clinical stage and the Zubrod-ECOG-WHO score. 303 (46.8%) patients received a total dose of 22.5 Gy in 3 fractions once a week, and 345 (53.2%) patients received a single fraction of 10 Gy. They were under clinical and endobronchial observation taking into consideration survival rates, local remission and duration of symptom relief such as dyspnoea, breathing, cough and haemoptysis.

Results

There was no difference in the length of survival time between the two groups of patients (log-rank test, p = 0.055). Patients showing improvement (objective response) survived longer than those who showed no change or progression (F Cox, p = 0.000001). In multivariate analysis the other statistically important prognostic factors were: clinical stage of primary tumor (F Cox, p = 0.000002), Zubrod-ECOG-WHO score (F Cox, p = 0.002) and age of patients (F Cox, p = 0.004).

Conclusions

The two treatment protocols showed similar efficiency in overcoming difficulties in breathing. Prognostic factors that significantly correlated with survival length were: grade of remission after treatment, clinical stage and performance status.     

The low incidence of secondary acute myelogenous leukaemia in children and adolescents treated with dexrazoxane for acute lymphoblastic leukaemia: a report from the Dana-Farber Cancer Institute ALL Consortium

Background

Dexrazoxane reduces the risk of anthracycline-related cardiotoxicity. In a study of children with Hodgkin lymphoma, the addition of dexrazoxane may have been associated with a higher risk for developing second malignant neoplasms (SMNs) including acute myelogenous leukaemia (AML) and myelodysplastic syndrome (MDS). We determined the incidence of SMNs in children and adolescents with acute lymphoblastic leukaemia (ALL) who were treated with dexrazoxane.

Methods

Between 1996 and 2010, the Dana-Faber Cancer Institute ALL Consortium conducted three consecutive multicentre trials for children with newly diagnosed ALL. In the first (1996-2000), high risk patients were randomly assigned to receive doxorubicin (30 mg/m²/dose, cumulative dose 300 mg/m²) preceded by dexrazoxane (300 mg/m²/dose, 10 doses), or the same dose of doxorubicin without dexrazoxane, during induction and intensification phases. In subsequent trials (2000-2005 and 2005-2010), all high risk and very high risk patients received doxorubicin preceded by dexrazoxane. Cases of SMNs were collected prospectively and were pooled for analysis. The frequency and 5-year cumulative incidence (CI) of SMNs were determined for patients who had received dexrazoxane.

Findings

Among 553 patients treated with dexrazoxane (1996-2000, N = 101; 2000-2005, N = 196; and 2005-2010, N = 256), the number of SMNs observed by protocol was 0 (median follow-up 9.6 years), 0 (median follow-up 5.2 years), and 1 (median follow-up 2.1 years). The only SMN was a case of AML, which developed in a patient with MLL-rearranged ALL 2.14 years after initial diagnosis. The overall 5-year CI of SMNs for all 553 patients was 0.24 ± 0.24%.

Interpretation

In a large population of children with high risk ALL who received dexrazoxane as a cardioprotectant drug, the occurrence of secondary AML was a rare event.     

Robotic system-based fractionated stereotactic radiotherapy in locally recurrent nasopharyngeal carcinoma

Purpose

We reviewed survival, local control, and toxicity in patients with locally recurrent nasopharyngeal carcinoma (NPC) who had been treated with fractionated stereotactic radiotherapy (FSRT).

Materials and methods

Between June 2002 and March 2008, we retrospectively reviewed 35 patients with locally recurrent NPC treated using FSRT with CyberKnife. Gross tumor volumes ranged from 2.6 to 64.0 ml (median, 7.9 ml). Radiation doses were prescribed at the isodose line (75-84% of the maximum dose; median, 80%). The prescribed dose of FSRT ranged from 24 to 45 Gy (median, 33 Gy) in three or five fractions.

Results

The overall survival (OS) rate, local failure-free survival (LFFS) rate, and disease progression-free survival (DPFS) rate at 5 years were 60%, 79%, and 74%, respectively. Twenty-three patients achieved complete response after FSRT. Only T stage at recurrence was an independent prognostic factor for OS and DPFS. Five patients exhibited severe late toxicity (Grade 4 or 5).

Conclusions

With regard to OS and LFFS, our study provided favorable outcomes. The incidence of severe late toxicities was acceptable in our study. FSRT would be considered as the alternative treatment of choice in re-irradiation for locally recurrent NPC.