Prognostic factors can guide the physician in selecting the optimal treatment for an individual patient. This study investigates the prognostic value of erythropoietin (EPO) and EPO receptor (EPO-R) ...expression of tumor cells for locoregional control and survival in non-small-cell lung cancer (NSCLC) patients.
Fourteen factors were investigated in 62 patients irradiated for stage II/III NSCLC, as follows: age, gender, Karnofsky performance score (KPS), histology, grading, TNM/American Joint Committee on Cancer (AJCC) stage, surgery, chemotherapy, pack years (average number of packages of cigarettes smoked per day multiplied by the number of years smoked), smoking during radiotherapy, hemoglobin levels during radiotherapy, EPO expression, and EPO-R expression. Additionally, patients with tumors expressing both EPO and EPO-R were compared to those expressing either EPO or EPO-R and to those expressing neither EPO nor EPO-R.
On univariate analysis, improved locoregional control was associated with AJCC stage II cancer (p < 0.048), surgery (p < 0.042), no smoking during radiotherapy (p = 0.024), and no EPO expression (p = 0.001). A trend was observed for a KPS of >70 (p = 0.08), an N stage of 0 to 1 (p = 0.07), and no EPO-R expression (p = 0.10). On multivariate analysis, AJCC stage II and no EPO expression remained significant. No smoking during radiotherapy was almost significant. On univariate analysis, improved survival was associated with N stage 0 to 1 (p = 0.009), surgery (p = 0.039), hemoglobin levels of ≥12 g/d (p = 0.016), and no EPO expression (p = 0.001). On multivariate analysis, N stage 0 to 1 and no EPO expression maintained significance. Hemoglobin levels of ≥12 g/d were almost significant. On subgroup analyses, patients with tumors expressing both EPO and EPO-R had worse outcomes than those expressing either EPO or EPO-R and those expressing neither EPO nor RPO-R.
EPO expression of tumor cells was an independent prognostic factor for locoregional control and survival in patients irradiated for NSCLC. EPO-R expression showed a trend. Patients with tumors expressing both EPO and EPO-R have an unfavorable prognosis.
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GEOZS, IJS, NUK, OILJ, UL, UM, UPUK
Abstract Purpose Carotid blowout (CB) is a serious complication in retreatment of neoplasms in the head and neck (H&N) region. Rates seem to increase in hypofractionated or accelerated ...hyperfractionated regimens. In this study, we investigate the CB rate and the cumulative doses received by the carotid artery (CA) in a cohort of patients who were reirradiated at CNAO with particle therapy in the H&N region. Methods and materials The dosimetric information, medical records, and tumor characteristics of 96 patients were analyzed. For 49 of these patients, the quality of dosimetric information was sufficient to calculate the cumulative doses to the CA. The corresponding biological equivalent dose in 2 Gy fractions (EQD2) was calculated with an α/β-ratio of 3. Results In the final reirradiation at CNAO, 17 patients (18%) had been treated with protons and 79 (82%) with carbon ions. Two patients experienced profuse oronasal bleeding, of which one case was confirmed to be caused by CB. If attributing both cases to CB, we found an actuarial CB rate of 2.7%. Interestingly, there were no CB cases in the carbon ion group even though this was the large majority of patients and they generally were treated more aggressively in terms of larger fraction doses and higher cumulative EQD2. Conclusions The current practice of particle reirradiation at CNAO for recurrent neoplasms in the H&N region results in acceptable rates of CB.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Much effort is currently being spent on developing anticancer drugs targeted at cellular signal transduction mechanisms, and several signal inhibitors have also been introduced into clinical ...practice. The rationale for such therapy is the realization that, in general, oncogenes and tumour suppressor genes encode proteins that are mutated or dysregulated forms of key components in major regulatory pathways. However, while we have witnessed striking clinical effects in certain malignancies, as in the treatment of chronic myelogeneous leukemia, the results in many other cancers have been rather disappointing, and this has raised the question of whether major advances can realistically be expected by the use of signal-targeted therapies on a broad scale. Here we briefly review the cellular and molecular basis for treatment with pharmacological signal inhibitors and the clinical experience with their use in different malignancies. We also discuss general strategies to improve the treatment, including approaches to the problem of resistance development. Clinical results vary greatly, from little or no treatment success in some cancers to an increasing number of examples of very promising responses. Progress has primarily been achieved in those malignancies and subsets of patients where the underlying molecular mechanisms have been explored in detail and the targets have been well defined. In conclusion, it is likely that novel signal-directed approaches will lead to further important advances in cancer therapy, but this will require continued efforts to identify targets that are oncogenic determinants, and systematic work to select patients for more individualized therapies.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
To investigate the incidence, time course, and relation to irradiated volumes of late morbidity after three-dimensional conformal radiation therapy (RT) for prostate cancer.
From January 2000 to ...December 2001, a total of 247 patients with prostate cancer received a target dose of 70 Gy using conformal RT. Forty-eight patients (20%) received irradiation to the prostate only (Group P), 154 patients (62%) received irradiation to the prostate and seminal vesicles (Group PSV), and 45 patients (18%) received modified pelvic fields (Group MPF). Androgen deprivation was given to 86% of patients. Median follow-up was 62 months. Late gastrointestinal (GI) and genitourinary (GU) morbidity were recorded according to the Radiation Therapy Oncology Group scoring system.
We observed 9%, 7%, and 25% Grade 2 or higher GI morbidity and 36%, 30%, and 21% Grade 2 or higher GU morbidity in Groups P, PSV, and MPF, respectively. In multivariate analyses, age and treatment group were independent predictors for the incidence of late Grade 2 or higher GI morbidity, whereas age and urinary symptoms before treatment were independent predictors for late Grade 2 or higher GU morbidity. Acute side effects predicted for late effects. The rectum dose-volume histogram parameters correlated with the incidence of late Grade 2 or higher GI morbidity, especially the fractional volume receiving more than 40-43 Gy. At 5 years of follow-up, the rate of Grade 2 late GI morbidity was only 1.4%, and Grade 2 or higher GU morbidity was 10.6%.
The data presented here show that late GI morbidity after prostate RT is low and subsides with time.
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GEOZS, IJS, NUK, OILJ, UL, UM, UPUK
This Nordic multicenter phase II study evaluated the efficacy and safety of oxaliplatin combined with the Nordic bolus schedule of fluorouracil (FU) and folinic acid (FA) as first-line treatment in ...metastatic colorectal cancer.
Eighty-five patients were treated with oxaliplatin 85 mg/m(2) as a 2-hour infusion on day 1, followed by a 3-minute bolus injection with FU 500 mg/m(2) and, 30 minutes later, by a bolus injection with FA 60 mg/m(2) every second week. The same doses of FU and FA were also given on day 2.
Fifty-one of 82 assessable patients achieved a complete (n = 4) or partial (n = 47) response, leading to a response rate of 62% (95% CI, 52% to 72%). Nineteen patients showed stable disease, and 12 patients had progressive disease. Thirty-eight of the 51 responses were radiologically confirmed 8 weeks later (confirmed response rate, 46%; 95% CI, 36% to 58%). The estimated median time to progression was 7.0 months (95% CI, 6.3 to 7.7 months), and the median overall survival was 16.1 months (95% CI, 12.7 to 19.6 months) in the intent-to-treat population. Neutropenia was the main adverse event, with grade 3 to 4 toxicity in 58% of patients. Febrile neutropenia developed in seven patients. Nonhematologic toxicity consisted mainly of neuropathy (grade 3 in 11 patients and grade 2 in another 27 patients).
Oxaliplatin combined with the bolus Nordic schedule of FU+FA (Nordic FLOX) is a well-tolerated, effective, and feasible bolus schedule as first-line treatment of metastatic colorectal cancer that yields comparable results compared with more complex schedules.
To elucidate changes in gene expression after treatment with regional thermochemoradiotherapy in locally advanced squamous cell cervical cancer.
Tru-Cut biopsy specimens were serially collected from ...16 patients. Microarray gene expression levels before and 24 h after the first and second trimodality treatment sessions were compared. Pathway and network analyses were conducted by use of Ingenuity Pathways Analysis (IPA; Ingenuity Systems, Redwood City, CA). Single gene expressions were analyzed by quantitative real-time reverse transcription-polymerase chain reaction.
We detected 53 annotated genes that were differentially expressed after trimodality treatment. Central in the three top networks detected by IPA were interferon alfa, interferon beta, and interferon gamma receptor; nuclear factor kappaB; and tumor necrosis factor, respectively. These genes encode proteins that are important in regulation cell signaling, proliferation, gene expression, and immune stimulation. Biological processes over-represented among the 53 genes were fibrosis, tumorigenesis, and immune response.
Microarrays showed minor changes in gene expression after thermochemoradiotherapy in locally advanced cervical cancer. We detected 53 differentially expressed genes, mainly involved in fibrosis, tumorigenesis, and immune response. A limitation with the use of serial biopsy specimens was low quality of ribonucleic acid from tumors that respond to highly effective therapy. Another "key limitation" is timing of the post-treatment biopsy, because 24 h may be too late to adequately assess the impact of hyperthermia on gene expression.
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GEOZS, IJS, NUK, OILJ, UL, UM, UPUK
Background and purpose: The clinical benefit of irradiating the intact breast after lumpectomy must be weighted against the risk of severe toxicity. We present a study on cardiac and pulmonary ...dose-volume data and the related complication probabilities of tangential breast irradiation having the following objectives: (1) to quantify the sparing of the organs at risk (ORs), the heart and the lung, achieved by three-dimensional (3-D) conformal tangential irradiation (CTI) as compared to standard tangential irradiation (STI); (2) to elucidate the uncertainty in radiation tolerance data; and (3) to analyse the relation between the amount of OR irradiated and the resulting morbidity risk.
Material and methods: Computed tomography (CT)-based 3-D treatment plans of 26 patients prescribed to CTI of the intact breast were applied. Contour-based STI has been our routine treatment, and was reconstructed for all patients. Dose–volume data and normal tissue complication probability (NTCP) predictions from the probit and relative seriality models with several cardiac and pulmonary tolerance parameterizations were analysed and compared.
Results and conclusions: A significant amount of normal tissues can be spared from radiation by using CT-based CTI, resulting in a 50% reduction of the average excess cardiac mortality risk in the left-sided cases. The risks for pericarditis and pneumonitis were too low to reveal any clinically significant difference between the treatments. For the STI set-up, a regression analysis showed that the excess cardiac mortality risk increased when larger parts of the heart were inside the fields. However, the different excess cardiac mortality and pneumonitis tolerance parameters resulted in statistically significant different NTCPs, which precluded the ability to accurately predict absolute NTCPs after tangential breast irradiation. Despite this uncertainty the different series of cardiac and pulmonary risk predictions were in relatively good agreement when small volumes of the ORs were irradiated. From the present data and without consideration of patient or organ motion, it therefore appears that tangential breast irradiation with less than 1 cm of the heart and 2–2.5 cm of the lung included inside the treatment fields will cause at most 1‰ risk for cardiac mortality and pulmonary morbidity. CT-based CTI should be considered, in particular for the left-sided cases, if these requirements cannot be met.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
•A never previously published 30 year old randomized clinical trial of the effect of adjuvant hyperthermia radiotherapy of locally advanced breast cancer.•The trial with 150+ patients demonstred that ...adjuvant hyperthermia significantly improved local control and cancer free survival.•The outcome was related to the quality of the heating.•The treatment was well tolerated.
The ESHO protocol 1–85 is a multicenter randomized trial initiated by the European Society for Hyperthermic Oncology with the aim to investigate the value of hyperthermia (HT) as an adjuvant to radiotherapy (RT) in treatment of locally advanced breast carcinoma. The trial is one of the largest studies of hyperthermia in radiotherapy but has not been previously published.
Between February 1987 and November 1993, 155 tumors in 151 patients were included. Tumors were stratified according to institution and size (T2-3/T4) and randomly assigned to receive radiotherapy alone (2 Gy/fx, 5 fx/wk) to a total dose of 65–70 Gy, incl. boost, or the same radiotherapy followed once weekly by hyperthermia (aimed for 43 °C for 60 min). Radiation was given with high voltage photons or electrons. The primary endpoint was persistent complete response (local control) in the treated area.
A total of 146 tumors in 142 patients were evaluable, with a median observation time of 19 (range 1–134) months. Seventy tumors were randomized to RT alone and 76 to RT + HT. Size was T4 in 92, and T2-3 in 54 tumors, respectively. The compliance to RT was good with all but 4 patients fulfilling the planned RT treatment. The tolerance to HT was fair, but associated with moderate to severe pain and discomfort in 15 % of the treatments. In 84 % of the heated patients a least one heat treatment achieved the target temperature, but the temperature variation was large. Addition of heat did not significantly increase the acute nor late radiation reactions.
Overall, the 5-year actuarial local failure rate was 57 %. Univariate analysis showed a significant influence of hyperthermia (RT alone 68 % versus RT + HT 50 %, p = 0.04, and T-size (T4 75 % versus T2-3 36 %, p < 0.01). A Cox multivariate analysis showed the same factors to be the only significant prognostic parameters: hyperthermia (HR: 0.61 0.38–0.98, and small tumor strata (HR: 0.46 0.26–0.92. Consequentially, more patients given RT + HT (36 %) survived without disease (DFS), than after RT alone (19 %), p = 0.021)
A randomized multicenter trial investigating the addition of a weekly hyperthermia treatment to radiotherapy of patients with locally advanced breast cancer significantly enhanced the 5-year tumor control and yielded more patients surviving free from cancer. The results substantiate the potential clinical benefit of hyperthermic oncology.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Physical activity is claimed to have a beneficial influence on a person's mental health, though its impact may be different in cancer patients and individuals in the general population. The objective ...of this cross-sectional study was (1) to estimate the associations between the level of self-reported physical activity as a lifestyle factor (LPA) and the prevalence of depression and anxiety disorder in testicular cancer survivors (TCSs) and in men of similar age from the general population (GenPop), and (2) to examine whether these associations differ in the two groups.
A total of 1260 TCSs and 20,207 men from the GenPop completed a questionnaire that assessed LPA, and depression and anxiety disorder on the Hospital Anxiety and Depression Scale (HADS).
The prevalence of HADS-defined depression was lower among those who were physically active than in those who were physically inactive (TCSs 9% vs 17%, P<0.001; GenPop 8% vs 15%, P<0.001). Among physically inactive TCSs there was a trend towards higher a prevalence of HADS-defined anxiety disorder compared to physically active TCSs (P=0.07). In the GenPop this difference was statistically significant (P<0.001). Multivariate analysis confirmed the association between LPA and HADS-defined depression in both the TCSs adjusted odds ratio (aOR)=0.56; 95% confidence interval (CI) (0.31, 1.02) and the GenPop aOR=0.58; 95% CI (0.51, 0.65), but not the association between LPA and HADS-defined anxiety disorder. The associations between LPA and HADS-defined depression and HADS-defined anxiety disorder did not differ between the TCSs and the GenPop.
In both the TCSs and the GenPop, the prevalence of HADS-defined depression was higher among those who were physically inactive than among those who were physically active, with no intergroup difference. There was no association between LPA and prevalence of HADS-defined anxiety disorder in either of the groups after adjusting for background variables. Prospective studies are needed to allow causal inferences to be drawn.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, ODKLJ, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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