Neurocognitive functioning and health-related behaviours in adult survivors of childhood cancer: a report from the Childhood Cancer Survivor Study

Background

Positive health-related behaviours are essential for the future wellbeing of childhood cancer survivors, though relatively few maintain healthy behaviours into adulthood.

Methods

Neurocognitive function and emotional distress were examined in 6,440 adult survivors from the Childhood Cancer Survivor Study, and used to predict rates of expected health-related behaviours. Covariates included cancer diagnosis, age, sex, body mass index, insurance status, income and antidepressant medication use, and multivariable models were constructed adjusting for these factors.

Findings

In multivariable regression models, survivors with neurocognitive problems in task efficiency (RR = 0.77, 95% CI = 0.72-0.84) were less likely to meet the Centers for Disease Control guidelines for weekly physical activity. Survivors with neurocognitive impairment were more likely to engage in general survivor care (RR = 1.20, 95% CI = 1.10-1.30), and less likely to engage in dental care (RR = 0.92, 95% CI = 0.88-0.97). Obese survivors were less likely to report receiving a bone density exam (RR = 0.67, 95% CI = 0.54-0.82), a mammogram (RR = 0.71, 95% CI = 0.57-0.89), and a skin exam (RR = 0.78, 95% CI = 0.68-0.89). Survivors reporting somatisation, i.e. vague physical symptoms associated with anxiety, were more likely to report receiving echocardiograms (RR = 1.53, 95% CI = 1.32-1.77).

Interpretation

These results support the link between neurocognitive and emotional problems and health-related behaviours in adult survivors of childhood cancer. Monitoring neurocognitive and emotional outcomes may help to identify survivors at risk for poor adherence to prescribed health behaviours and health screening exams.     

Haematologic toxicities associated with the addition of bevacizumab in cancer patients

Background

Bevacizumab is currently approved for the treatment of several malignancies. Haematologic toxicities are not among the main concerns associated with bevacizumab, but they have been occasionally reported. We performed a meta-analysis to determine the incidence and risk of haematologic toxicities associated with bevacizumab.

Methods

Pubmed databases from 1966 to September 2010 were searched for studies reported, as well as American Society of Clinical Oncology meetings. Bevacizumab randomised clinical trials with adequate safety data profile were included. Statistical analyses were conducted to calculate the summary incidence, relative risk (RR) and 95% confidence intervals (CI).

Results

15,263 patients were included. The incidence of bevacizumab-associated all-grade and high-grade haematologic toxicities were, respectively: anaemia: 18.7% and 3.9%; neutropenia: 25.0% and 18.5%; and thrombocytopenia: 13.9% and 3.4%. Febrile neutropenia incidence was 3.8%. Compared to placebo/control arms, bevacizumab was associated with a decreased risk of all-grade (RR = 0.81; 95%CI 0.68-0.96; p = .016) and high-grade (RR = 0.73; 95%CI 0.60-0.89; p = .002) anaemia, and increased risks of all-grade (RR = 1.15; 95%CI 1.01-1.30; p = .033) and high-grade (RR = 1.08; 95%CI 1.02-1.13; p = .005) neutropenia, all-grade thrombocytopenia (RR = 1.22; 95%CI 1.00-1.48; p = .047) and febrile neutropenia (RR = 1.31; 95%CI 1.08-1.58; p = .006).

Conclusions

Bevacizumab is associated with a lower risk of anaemia and increased risks of neutropenia, thrombocytopenia and febrile neutropenia.     

Constitutive expression of γ-H2AX has prognostic relevance in triple negative breast cancer

Background and purpose

Constitutive γ-H2AX expression might indicate disruption of the DNA damage repair pathway, genomic instability, or shortened telomeric ends. Here, we quantified expression of endogenous γ-H2AX and its downstream factor 53BP1 in a large number of breast cancer cell lines (n = 54) and a node-negative breast cancer cohort that had not received adjuvant systemic treatment (n = 122).

Materials and methods

Formalin fixed paraffin embedded breast cancer cell lines and tumors were immunohistochemically analyzed for γ-H2AX and 53BP1 expression, and related to cell line, patient and tumor characteristics and to disease progression.

Results

In breast cancer cell lines, γ-H2AX positivity was associated with the triple negative/basal like subgroup (p = 0.005), and with BRCA1 (p = 0.011) or p53 (p = 0.053) mutations. Specifically in triple negative breast cancer patients a high number of γ-H2AX foci indicated a significantly worse prognosis (p = 0.006 for triple negative vs. p = 0.417 for estrogen receptor (ER), progesterone receptor (PR) or HER2 positive patients). A similar association with disease progression was found for 53BP1. In a multivariate analysis with tumor size, grade, and triple negativity, only the interaction between triple negativity and γ-H2AX remained significant (p = 0.002, Hazard Ratio = 6.77, 95% CI = 2.07-22.2).

Conclusions

Constitutive γ-H2AX and 53BP1 staining reveals a subset of patients with triple negative breast tumors that have a significantly poorer prognosis.     

Risk of cardiac dysfunction with trastuzumab in breast cancer patients: a meta-analysis

Background

Trastuzumab is used widely for the treatment of early and advanced breast cancer. However, concerns have arisen regarding its cardiac toxicity. We did a systematic review and meta-analysis of published randomized controlled trials (RCTs) to assess the overall risk of cardiac dysfunction associated with trastuzumab treatment.

Methods

We searched PubMed and Web of Science (January 1966-July 2009) and American Society of Clinical Oncology conferences held (January 2000-July 2009) for relevant articles and abstracts. Summary incidence rates, relative risks (RRs), and 95% confident intervals (CIs) were calculated using a fixed-effects or random-effects model.

Results

11,882 patients from 10 RCTs were included for analysis. The incidences of LVEF decrease and congestive heart failure (CHF) were 7.5% (95% CI 4.2-13.1) and 1.9% (95% CI 1.0-3.8) among patients receiving trastuzumab. Trastuzumab significantly increased the risk of LVEF decrease (RR = 2.13, 95% CI, 1.31-3.49; p = 0.003). In addition, it significantly increased the risk of CHF (RR = 4.19, 95% CI 2.73-6.42; p < 0.00001). The increased risk of CHF was observed in patients with early stage (RR = 4.05, 95% CI 2.49-6.58; p < 0.00001) as well as metastatic disease (RR = 4.75, 95% CI 1.93-11.71; p = 0.0007). Furthermore, trastuzumab significantly increased the risk of CHF (RR = 4.27, 95% CI 2.75-6.61, p < 0.00001) in patients receiving anthracycline-based chemotherapy, but not in patients receiving non-anthracycline chemotherapy (RR = 2.42, 95% CI 0.36-16.19, p = 0.36).

Conclusion

The addition of trastuzumab to anthracycline-based chemotherapy significantly increase the risk of cardiac dysfunction in breast cancer patients. Further studies are recommended for non-anthracycline chemotherapy.     

Analysis of acute radiation-induced esophagitis in non-small-cell lung cancer patients using the Lyman NTCP model

Purpose

To analyze acute esophagitis (AE) in a Chinese population receiving 3D conformal radiotherapy (3DCRT) for non-small cell lung cancer (NSCLC), combined or not with chemotherapy (CT), using the Lyman-Kutcher-Burman (LKB) normal tissue complication probability (NTCP) model.

Materials and methods

157 Chinese patients (pts) presented with NSCLC received 3DCRT: alone (34 pts) or combined with sequential CT (59 pts) (group 1) or with concomitant CT (64 pts) (group 2). Parameters (TD₅₀, n, and m) of the LKB NTCP model predicting for > grade 2 AE (RTOG grading) were identified using maximum likelihood analysis. Univariate and multivariate analyses using a binary regression logistic model were performed to identify patient, tumor and dosimetric predictors of AE.

Results

Grade 2 or 3 AE occurred in 24% and 52% of pts in group 1 and 2, respectively (p < 0.001). For the 93 group 1 pts, the fitted LKB model parameters were: m = 0.15, n = 0.29 and TD₅₀ = 46 Gy. For the 64 group 2 pts, the parameters were: m = 0.42, n = 0.09 and TD₅₀ = 36 Gy. In multivariate analysis, the only significant predictors of AE were: NTCP (p < 0.001) and V₅₀, as continuous variable (RR = 1.03, p = 0.03) or being more than a threshold value of 11% (RR = 3.6, p = 0.009).

Conclusions

A LKB NTCP model has been established to predict AE in a Chinese population, receiving thoracic RT, alone or combined with CT. The parameters of the models appear slightly different than the previous one described in Western countries, with a lower volume effect for Chinese patients.     

Quality of care indicators and their related outcomes: A population-based study in prostate cancer patients treated with radiotherapy

Background and purpose

We describe variations across the regional cancer centres in Ontario, Canada for five prostate cancer radiotherapy (RT) quality indicators: incomplete pre-treatment assessment, follow-up care, leg immobilization, bladder filling, and portal film target localization. Along with cancer centre volume, we examined each indicator’s association with relevant outcomes: long-term cause-specific survival, urinary incontinence, and gastrointestinal and genitourinary late morbidities.

Materials and methods

We conducted a population-based retrospective cohort study of 924 prostate cancer patients diagnosed between 1990 and 1998 who received RT within 9 months of diagnosis. Data sources included treating charts and registry and administrative data. The associations between indicators and outcomes were analysed using regression techniques to control for potential confounders.

Results

Practice patterns varied across the regional cancer centres for all indicators (p < 0.0001). Incomplete pre-treatment assessment was associated with worse cause-specific survival although this result was not significant when adjusted for confounding (adjusted RR = 1.78, 95% CI = 0.79–3.98). Treatment without leg immobilization (adjusted RR = 1.72, 95% CI = 1.16–2.56) and with an empty bladder (adjusted RR = 1.98, 95% CI = 1.08–3.63) was associated with genitourinary late morbidities. Treatment without leg immobilization was also associated with urinary incontinence (adjusted RR = 2.18, 95% CI = 1.23–3.87).

Conclusions

We documented wide variations in practice patterns. We demonstrated that measures of quality of care can be shown to be associated with clinically relevant outcomes in a population-based sample of prostate cancer patients.     

Minimal impact of postmastectomy radiation therapy on locoregional recurrence for breast cancer patients with 1 to 3 positive lymph nodes in the modern treatment era

Introduction

Given modern treatment strategies, controversy remains regarding whether postmastectomy radiation therapy (PMRT) is necessary for breast cancer patients with 1–3 positive axillary lymph nodes (ALN). Our aim was to assess the significance of PMRT in the modern treatment era for these patients.

Mini Nutritional Assessment (MNA) and biochemical markers of cachexia in metastatic lung cancer patients: interrelations and associations with prognosis

Purpose

Lung cancer patients frequently present with weight loss in the context of the cachexia syndrome. Despite its high clinical significance, definite diagnostic criteria of cachexia are lacking. Nutritional screening questionnaires, like the Mini Nutritional Assessment (MNA), have been proposed for the timely diagnosis of the syndrome. The aim of this study was to evaluate the correlation of MNA with laboratory markers of inflammation/cachexia in patients with metastatic lung cancer. The prognostic value of the measured parameters was also examined.

Patients and methods

Patients with metastatic lung cancer referred for systemic therapy were eligible. Baseline clinical characteristics were recorded and nutritional status was assessed using MNA. Blood samples were also collected and the following parameters were measured: hemoglobin (Hb), albumin (Alb), C-reactive protein (CRP), ghrelin, adiponectin, leptin and insulin growth factor I (IGF-I).

Results

Totally, 115 patients (101 males) [median age 66 years (range 32-86)] were evaluated. According to MNA score, 27 (23.5%) patients were well nourished, 59 (51.3%) were at nutritional risk and 29 (25.2%) were already malnourished at diagnosis. MNA correlated with the following parameters: Hb (p = 0.001), albumin (p < 0.001), CRP (p = 0.002), adiponectin (p = 0.037) and leptin (p = 0.008). After a median follow up of 38.2 months, multivariate analysis revealed that age (p = 0.008), number of metastatic sites (p < 0.001), MNA (p = 0.044) and leptin (p = 0.004) independently correlated with overall survival.

Conclusions

Based on the MNA, the majority of patients were either malnourished or at nutritional risk. MNA correlated with laboratory parameters related to inflammation/cachexia and was independently associated with survival.     

Postmastectomy intensity modulated radiation therapy following immediate expander-implant reconstruction

Background/purpose

To evaluate radiation plans of patients undergoing mastectomy with immediate expander-implant reconstruction followed by postmastectomy radiation therapy (PMRT).

Materials/methods

We identified 41 patients from June 2004 to May 2007 who underwent mastectomy, immediate expander-implant reconstruction, and PMRT with intensity-modulated radiation therapy. We assessed chest wall (CW) coverage and volume of heart and lung irradiated.

Results

In 73% of patients, all CW borders were adequately covered, and in 22%, all but 1 border were adequately covered. The total lung V₂₀ was <20% in 39/41 patients. The mean lung V₂₀ was 13% (range, 3-23%), and the mean heart D_mean was 2.81 Gy (range, 0.53-9.60 Gy). In patients with left-sided lesions without internal mammary nodes (IMNs) treatment (n = 22), the mean lung V₂₀ was 12.6% and the mean heart D_mean was 3.90 Gy, and in the patient with IMN treatment, the lung V₂₀ was 18% and heart D_mean was 8.04 Gy. For right-sided lesions without IMN treatment (n = 12), the mean lung V₂₀ was 12.4% and the mean heart D_mean was 0.90 Gy, and in patients with IMN treatment (n = 6), these numbers were 17.8% and 1.76 Gy. At a median follow-up of 29 months, the 30-month actuarial local control was 97%.

Conclusions

In women undergoing immediate expander-implant reconstruction, PMRT can achieve excellent local control with acceptable heart and lung doses. These results can be achieved even when the IMN are being treated, although doses to the heart and lungs will be higher.     

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.     

Lymph node micrometastasis in node negative early gastric cancer

Aims

The clinical significance of lymph node micrometastasis for histologically node negative gastric cancer is not well documented. This study was to assess the incidence and to clarify the risk factors of lymph node micrometastasis in patients with node negative early gastric cancer (EGC).

Methods

We investigated the lymph node micrometastasis with using an anticytokeratin immunohistochemical stain in 90 patients with node negative EGC who underwent curative resection between 1991 and 2000.

Results

Among 3526 nodes from 90 patients, there were 17 cytokeratin immunohistochemical stain positive nodes from nine patients. The incidence of micrometastasis was higher in patients with lymphatic invasion (p = 0.012), venous invasion (p = 0.026) and larger tumor (p = 0.003). The independent risk factors for lymph node micrometastasis were lymphatic invasion (p = 0.004, RR = 22.915, 95% CI = 2.709 ∼ 193.828) and tumor size (p = 0.029, RR = 1.493, 95% CI = 1.042 ∼ 2.138). Although there were 10 deaths during the follow-up period of mean 67.6 months (1 month ∼ 147 months), there was no death from a cancer recurrence.

Conclusions

The incidence of lymph node micrometastasis in patients with node negative early gastric cancer was 10%, and the independent risk factors for micrometastasis were lymphatic invasion and tumor size.     

Prevalence of BRAF V600E mutation in Chinese melanoma patients: large scale analysis of BRAF and NRAS mutations in a 432-case cohort

Background

Mutations of NRAS and BRAF have been described in Caucasian melanomas. However, the status and the clinical significance of BRAF and NRAS mutations in the Asian population have not been investigated on a large scale.

Methods

Melanoma samples (n = 432) were analysed for mutations in exons 11 and 15 of the BRAF gene, and exons 1 and 2 of the NRAS gene in genomic DNA by polymerase chain reaction (PCR) amplification and Sanger sequencing. Mutations of BRAF and NRAS genes were correlated to clinicopathologic features and prognosis of the patients.

Results

The incidence of somatic mutations within the BRAF and NRAS genes was 25.5% (110/432) and 7.2% (31/432), respectively. Among the 110 patients with BRAF mutations, 98 patients (89.1%) had V600E mutations. Melanomas without chronic sun-induced damage (Non-CSD) were more likely (P < 0.01) to show BRAF mutations while NRAS mutation frequency was unbiased between melanoma subtypes. Patients with genetic mutations in BRAF (P < 0.01) or NRAS (P = 0.04) gene are more likely to have ulceration as compared to patients without BRAF or NRAS mutations, respectively. Both BRAF (P = 0.003) and NRAS mutations (P = 0.031) are inversely correlated to overall survival.

Conclusions

BRAF mutation is frequent while mutations in NRAS gene are rare. The most prevalent BRAF mutation type is V600E. Patients with mutations in BRAF or NRAS gene are frequently present with ulceration, and mutation in BRAF or NRAS gene is indicator for poor prognosis. Our study may warrant a clinical trial of kinase inhibitors targeting BRAF V600E in Chinese and Asian melanoma patients.     

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

Purpose

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

Materials and methods

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

Results

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

Conclusions

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

Effect of local therapy on locoregional recurrence in postmenopausal women with breast cancer in the Tamoxifen Exemestane Adjuvant Multinational (TEAM) trial

Background and purpose

The TEAM trial investigated the efficacy and safety of adjuvant endocrine therapy consisting of either exemestane or the sequence of tamoxifen followed by exemestane in postmenopausal hormone-sensitive breast cancer. The present analyses explored the association between locoregional therapy and recurrence (LRR) in this population.

Material and methods

Between 2001 and 2006, 9779 patients were randomized. Local treatment was breast conserving surgery plus radiotherapy (BCS + RT), mastectomy without radiotherapy (MST-only), or mastectomy plus radiotherapy (MST + RT). Patients with unknown data on surgery, radiotherapy, tumor or nodal stage (n = 199), and patients treated by lumpectomy without radiotherapy (n = 349) were excluded.

Results

After a median follow-up of 5.2 years, 270 LRRs occurred (2.9%) among 9231 patients. The 5-years actuarial incidence of LRR was 4.2% (95% CI 3.3–4.9%) for MST-only, 3.4% (95% CI 2.4–4.2%) for MST + RT and 1.9% (95% CI 1.5–2.3%) for BCS + RT. After adjustment for prognostic factors, the hazard ratio (HR, reference BCS + RT) for LRR remained significantly higher for MST-only (HR 1.53; 95% CI 1.10–2.11), not for MST + RT (HR 0.78; 95% CI 0.50–1.22).

Conclusion

This explorative analysis showed a higher LRR risk after MST-only than after BCS + RT, even after adjustment for prognostic factors. As this effect was not seen for MST + RT versus BCS + RT, it might be explained by the beneficial effects of radiation treatment.     

The Cambridge post-mastectomy radiotherapy (C-PMRT) index: A practical tool for patient selection

Background and purpose

Post mastectomy radiotherapy (PMRT) reduces loco-regional recurrence (LRR) and has been associated with survival benefit. It is recommended for patients with T3/T4 tumours and/or ?4 positive lymph nodes (LN). The role of PMRT in 1–3 positive LN and LN negative patients is contentious. The C-PMRT index has been designed for selecting PMRT patients, using independent prognostic factors for LRR. This study reports a 10 year experience using this index.

Materials and methods

The C-PMRT index was constructed using the following prognostic factors (a) number of positive LN/lymphovascular invasion, (b) tumour size (c) margin status and (d) tumour grade. Patients were categorised as high (H) risk, intermediate (I) risk and low (L) risk. PMRT was recommended for H and I risk patients. The LRR, distant metastasis and overall survival (OS) rates were measured from the day of mastectomy.

Results

From 1999 to 2009, 898 invasive breast cancers in 883 patients were treated by mastectomy (H: 323, I: 231 and L: 344). At a median follow up of 5.2 years, 4.7% (42/898) developed LRR. The 5-year actuarial LRR rates were 6%, 2% and 2% for the H, I and L risk groups, respectively. 1.6% (14/898) developed isolated LRR (H risk n = 4, I risk group n = 0 and L risk n = 10). The 5-year actuarial overall survival rates were 67%, 77% and 90% for H, I and L risk groups, respectively.

Conclusion

Based on published literature, one would have expected a higher LRR rate in the I risk group without adjuvant RT. We hypothesise that the I risk group LRR rates have been reduced to that of the L risk group by the addition of RT. Apart from LN status and tumour size, other prognostic factors should also be considered in selecting patients for PMRT. This pragmatic tool requires further validation.     

Poorer outcome in Polynesian patients with prostate cancer treated with definitive conformational radiation therapy

Purpose

To compare freedom from biochemical failure (FFBF) of French Polynesian (FP) and Native European (NE) prostate cancer patients after definitive conformal radiotherapy (RT).

Patients and methods

Data were reviewed from medical records of 152 consecutive patients (46 FP and 106 NE) with clinically localised prostate cancer treated with definitive RT. Neoadjuvant androgen deprivation therapy (ADT) was used in 22% of cases. Definition for biochemical failure was a rise by 2 ng/mL or more above the nadir prostate-specific antigen (PSA) level. The median follow-up was 34 months.

Results

In comparison to NE patients, FP patients were younger (p = 0.002) with a higher low-risk proportion (p = 0.06). Probability of 5-year FFBF was 77% in the NE cohort and 58.0% in the FP cohort (p = 0.017). Univariate analysis showed that FP ethnicity was associated with worse prognosis in high-risk tumours (p = 0.004). Cox multivariate analysis showed that factors associated with FFBF were risk category (p < 0.017), and FP origin (p = 0.03), independently of ADT and radiation dose.

Conclusion

FP ethnicity was an independent prognostic factor for biochemical relapse after definitive conformal RT for prostate cancer.     

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.     

A randomized trial on addition of concurrent-adjuvant chemotherapy and/or accelerated fractionation for locally-advanced nasopharyngeal carcinoma

Background and purpose

To evaluate the therapeutic benefits by adding chemotherapy (+C) and/or accelerated-fractionation (AF) for patients with T3-4N0-1M0 nasopharyngeal carcinoma.

Materials and methods

From 1999 to 2004, 189 eligible patients were randomized to one of four treatment groups (CF/CF + C/AF/AF + C). The number of fractions/week was 5 for the CF groups and 6 for the AF groups. Patients in the +C groups were given concurrent cisplatin plus adjuvant cisplatin and fluorouracil.

Results

The AF + C group achieved significantly higher failure-free rate (88% at 5-year) than the CF group (63%; p = 0.013), the AF group (56%; p = 0.001) and the CF + C group (65%; p = 0.027). As compared with CF alone, the increase in late toxicity was statistically insignificant (36% vs. 20%; p = 0.25). Deaths due to cancer progression decreased (7% vs. 33%; p = 0.011) but deaths due to incidental causes increased (9% vs. 2%; p = 0.62). Improvement in overall survival reached borderline significance (85% vs. 66%; p = 0.058).

Conclusions

Concurrent-adjuvant chemotherapy combined with AF significantly reduced failure and cancer-specific deaths. Although the increase in major late toxicity and incidental deaths were statistically insignificant, a subtle increase in non-cancer deaths narrowed the overall survival gain.     

Impact of target volumes and radiation technique on loco-regional control and survival for patients with unilateral cervical lymph node metastases from an unknown primary

Purpose

To compare the impact of an unilateral post-operative irradiation or a bilateral irradiation in terms of loco-regional control and survival in patients with cervical lymph node of squamous cell carcinoma from an unknown primary (CUP).

Methods and materials

Ninety five patients with epidermoid carcinoma involving unilateral cervical lymph nodes from an unknown primary were treated in two institutions from 1990 to 2007. Post-operative radiation therapy was delivered to one side of the neck in 59 cases, to both sides of the neck in 36 cases. There were 11 women and 84 men ranging in age from 38 to 80 years (median 59 years). Neck dissection was performed in 79 patients while 16 patients underwent single lymph node sampling only.

Results

After a median follow-up of 3.3 years, the nodal relapse rate was 34% after unilateral neck irradiation and 25% after bilateral radiotherapy (p = 0.21). Six contralateral lymph node relapses occurred after unilateral irradiation (10%). The 5-year overall survival rate of the entire group was 24%. The 5-year OS rates were 22% after unilateral irradiation and 23%, after bilateral radiotherapy (p = 0.944). The occult primary occurred in 12% after unilateral irradiation and 6% after bilateral radiotherapy. The radiation technique (3D-CRT or IMRT vs. 2D: p = 0.026) was prognostic on loco-regional control. Independent prognostic determinants on overall survival were the WHO status (p = 0.013) and the radiation technique (2D vs. 3D-CRT or IMRT; p = 0.029). There was no difference in loco-regional control (p = 0.639) and no difference in survival (p = 0.493) when chemotherapy was associated.

Conclusions

Retrospective comparisons between bilateral and unilateral neck radiotherapies did not show differences in terms of loco-regional control and survival. However, patient’s local regional control and survival are significantly improved after 3D-CRT or IMRT.     

Malignant mucosal melanoma treated with carbon ion radiotherapy with concurrent chemotherapy: Prognostic value of pretreatment apparent diffusion coefficient (ADC)

Background and purpose

To evaluate the potential of apparent diffusion coefficient (ADC) value before carbon ion radiotherapy (C-ion RT) for malignant mucosal melanoma (MMM) to predict prognosis.

Materials and methods

We recruited 37 patients with MMM in the head and neck treated by C-ion RT with concomitant chemotherapy. Univariate and multivariate analyses of minimum ADC, mean ADC, tumor volume, age, PS, and gender were performed to identify prognostic factors.

Results

The 3-year local control rate, distant metastasis-free survival rate and overall survival rate of all patients were 81.1%, 37.6% and 65.3%, respectively, with a median follow-up period of 19.0 months. In univariate analyses, lower minimum ADC (?0.6380 × 10⁻³ mm²/s) and lower mean ADC (?1.1523 × 10⁻³ mm²/s) were unfavorable prognostic factors for distant metastasis (p = 0.029 and p = 0.014, respectively), and lower minimum ADC was an unfavorable prognostic factor for overall survival (p = 0.019). However, there was no significant prognostic factor of local control including ADC value. In multivariate analyses, only minimum ADC was selected as a prognostic factor of distant metastasis-free survival and overall survival (p = 0.015 and p = 0.006, respectively).

Conclusion

Minimum ADC can be a prognostic factor of MMM in the head and neck after C-ion RT.