Concomitant chemo-radiotherapy for unresectable oesophageal cancer: A mono-institutional study on 40 patients

Background/AimTo analyse clinical response, overall (OS) and disease free survival (DFS) and toxicity in patients with unresectable oesophageal cancer treated by concomitant chemo-radiotherapy (CRT).Materials and methodsForty patients with stage IIa–IVa biopsy proven oesophageal carcinoma were treated with CRT. All patients were studied with endoscopy and CT and judged unresectable after multidisciplinary discussion. CRT consisted of 3 cycles of cisplatin 100 mg/m² or carboplatin 300 mg/m² on day 1 and 5-fluorouracil 1000 mg/m² as a continuous infusion of 96 h associated with concurrent 3D-conformal RT. By using 15 MeV X-rays, a total dose of 60–66 Gy was delivered with daily fractions of 1.8–2.0 Gy.ResultsComplete response (CR), partial response (PR) and no response (NR) were observed in 50%, 20% and 20% of cases, respectively. Of the 20 patients with CR, 15 developed loco-regional recurrent disease. OS and DFS rates at 3 and 5 years were 38%, 8%, 49% and 10%, respectively. Total radiation dose ≥60 Gy improved loco-regional control and complete response (CR vs. PR + NR; p = 0.004) influenced both DFS and loco-regional control. Grade 3 gastrointestinal and haematological acute toxicity occurred in 3/40 patients (7.5%). One patient developed grade 4 renal failure. Late toxicity was reported in 2/40 patients (5.0%), consisting of grade 3 radiation pneumonitis.ConclusionsConcomitant CRT for unresectable oesophageal cancer can result in an acceptable loco-regional control with limited toxicity. Response after treatment and total radiation dose influenced the outcome.     

Comparison of neoadjuvant oral chemotherapy with UFT plus Folinic acid or Capecitabine concomitant with radiotherapy on locally advanced rectal cancer

AimTo evaluate the differences in treatment response and the impact on survival with both oral agents (UFT and Capecitabine) as neoadjuvant chemotherapy administered concomitantly with radiotherapy.BackgroundThere are still no studies comparing the use of neoadjuvant oral chemotherapy either with UFT plus Folinic acid or Capecitabine concomitant with radiotherapy in locally advanced rectal cancer (LARC).Materials and methodsA set of 112 patients with LARC were treated preoperatively. GROUP 1 – 61 patients underwent concomitant oral chemotherapy with Capecitabine (825 mg/m² twice daily). GROUP 2 – 51 patients submitted to concomitant oral chemotherapy with UFT (300 mg/m²/d) + Folinic acid (90 mg/d) and radiotherapy. 57.1% of patients were submitted to adjuvant chemotherapy.ResultsGROUP 1: acute toxicity – 80.3%; pathological complete response (pCR) – 10.5%; tumor downstaging (TD) – 49.1%; nodal downstaging (ND) – 76.5%; loco-regional response (LRR) – 71.9%; toxicity to adjuvant chemotherapy – 75%. GROUP 2: acute toxicity – 80.4%; pCR – 28%; TD – 62%; ND – 75.6%; LRR – 78%; toxicity to adjuvant chemotherapy – 56%. There was no difference in survival nor loco-regional control between the groups.ConclusionsPatients treated with neoadjuvant oral UFT + Folinic acid had a higher rate of pathologic complete response than patients treated with Capecitabine concomitant with radiotherapy. There were no differences in downstaging, LRR, toxicity, survival or loco-regional control between both groups. There was a trend to a higher rate of toxicity to adjuvant chemotherapy in the Capecitabine group.     

In vivo skin dose measurement using MOSkin detectors in tangential breast radiotherapy

The purpose of this study is to measure patient skin dose in tangential breast radiotherapy. Treatment planning dose calculation algorithm such as Pencil Beam Convolution (PBC) and in vivo dosimetry techniques such as radiochromic film can be used to accurately monitor radiation doses at tissue depths, but they are inaccurate for skin dose measurement. A MOSFET-based (MOSkin) detector was used to measure skin dose in this study. Tangential breast radiotherapies (“bolus” and “no bolus”) were simulated on an anthropomorphic phantom and the skin doses were measured. Skin doses were also measured in 13 patients undergoing each of the techniques. In the patient study, the EBT2 measurements and PBC calculation tended to over-estimate the skin dose compared with the MOSkin detector (p < 0.05) in the “no bolus radiotherapy”. No significant differences were observed in the “bolus radiotherapy” (p > 0.05). The results from patients were similar to that of the phantom study. This shows that the EBT2 measurement and PBC calculation, while able to predict accurate doses at tissue depths, are inaccurate in predicting doses at build-up regions. The clinical application of the MOSkin detectors showed that the average total skin doses received by patients were 1662 ± 129 cGy (medial) and 1893 ± 199 cGy (lateral) during “no bolus radiotherapy”. The average total skin doses were 4030 ± 72 cGy (medial) and 4004 ± 91 cGy (lateral) for “bolus radiotherapy”. In some cases, patient skin doses were shown to exceed the dose toxicity level for skin erythema. Hence, a suitable device for in vivo dosimetry is necessary to accurately determine skin dose.     

Occupational exposure to hexavalent chromium and cancers of the gastrointestinal tract: A meta-analysis

Introduction: We conducted a systematic literature review and meta-analysis of oral cavity, esophageal, stomach, small intestine, colon, and rectal cancers among workers occupationally exposed to Cr(VI). Methods: Using PubMed, studies published from 1950 to 2009 evaluating the relationship between Cr(VI) exposure and GI cancers were identified. Measures of effect and variability were extracted from 32 studies meeting specific inclusion criteria, and meta-analysis summary relative risk measures were calculated using random effects models and inverse variance weighting methods. Results: Meta-standardized mortality ratios (SMRs) were, for cancer of the: oral cavity [1.02 (95% CI = 0.77–1.34)]; esophagus [1.17 (95% CI = 0.90–1.51)]; stomach [1.09 (95% CI = 0.93–1.28)]; colon [0.89 (95% CI = 0.70–1.12)]; and rectum [1.17 (95% CI = 0.98–1.39)]. Analyses of more highly exposed subgroups included in the studies or subgroups based on geographic region or by industry with recognized Cr(VI) exposures (welding, chrome plating, chromate production, and pigment production) did not result in elevated meta-SMRs except for esophageal cancer among US cohorts [meta-SMR = 1.49 (95% CI = 1.06–2.09)]. However, that finding was based on a subgroup of only four studies, one of which was a PMR study. Potential confounding by socioeconomic status (SES), diet and/or smoking, or limitations due to the healthy-worker effect (HWE) were evaluated, and while smoking, diet and SES may be important factors that may have upwardly biased the meta-SMRs, HWE is not likely to have significantly affected the summary results. None of three studies reporting small intestine cancers observed a statistically significant increased risk. Discussion: These meta-analyses and literature review indicate that Cr(VI)-exposed workers are not at a greater risk of GI cancers than the general population.     

Postoperative endometrial carcinoma treated with external beam irradiation plus vaginal-cuff brachytherapy. Is there a dose relationship with G2 vaginal complications?

AimTo analyse the possible relationship between the EQD2_(α/β=3Gy) at 2 cm³ of the vagina and late toxicity in vaginal-cuff-brachytherapy (VBT) after external-beam-irradiation (EBRT) for postoperative endometrial carcinoma (EC).Materials and methodsFrom 2014 to 2016, 62 postoperative EC patients were treated with EBRT + VBT. The median EBRT dose was 45 Gy (44 Gy–50.4 Gy). VBT involved a single 7 Gy dose. Toxicity was prospectively evaluated using the RTOG score for the rectum and bladder and the objective LENT-SOMA criteria for the vagina. EQD2_{(α/β = 3Gy)} at 2 cm³ of the most exposed part of the vagina was calculated by the sum of the EBRT + VBT dose. Statistics: Boxplot, Student’s t and Chi-square tests and ROC curves.ResultsMean follow-up: 39.2 months (15–68). Late toxicity: bladder:0 patient; rectum:2 patients-G1; Vagina: 26 patients-17G1, 9G2; median EQD2_(α/β=3Gy) at 2 cm³ in G0-G1 patients was 70.4 Gy(SD2.36), being 72.5 Gy(SD2.94) for G2p. The boxplot suggested a cut-point identifying the absence of G2: 100 % of G2p received >68 Gy, ROC curves showed an area under the curve of 0.72 (sensitivity of 1 and specificity of 0.15).ConclusionsDoses >68 Gy EQD2_(α/β=3Gy) at 2 cm³ to the most exposed area of the vagina were associated with late G2 vaginal toxicity in postoperative EC patients treated with EBRT + VBT suggesting a very good dose limit to eliminate the risk of G2 late toxicity. The specificity obtained indicates the need for prospective analyses.     

Monte Carlo study on the secondary cancer risk estimations for patients undergoing prostate radiotherapy: A humanoid phantom study

AimThe aim of this study was to estimate the secondary malignancy risk from the radiation in FFB prostate linac-based radiotherapy for different organs of the patient.BackgroundRadiation therapy is one of the main procedures of cancer treatment. However, the application the radiation may impose dose to organs of the patient which can be the cause of some malignancies.Materials and methodsMonte Carlo (MC) simulation was used to calculate radiation doses to patient organs in 18 MV linear accelerator (linac) based radiotherapy. A humanoid MC phantom was used to calculate the equivalent dose s for different organs and probability of secondary cancer, fatal and nonfatal risk, and other risks and parameters related to megavoltage radiation therapy. In out-of-field radiation calculation, it could be seen that neutrons imparted a higher dose to distant organs, and the dose to surrounding organs was mainly due to absorbed scattered photons and electron contamination.ResultsOur results showed that the bladder and skin with 54.89 × 10⁻³ mSv/Gy and 46.09 × 10⁻³ mSv/Gy, respectively, absorbed the highest equivalent dose s from photoneutrons, while a lower dose was absorbed by the lung at 3.42 × 10⁻³ mSv/Gy. The large intestine and bladder absorbed 55.00 × 10⁻³ mSv/Gy and 49.08 × 10⁻³, respectively, which were the highest equivalent dose s due to photons. The brain absorbed the lowest out-of-field dose, at 1.87 × 10⁻³ mSv/Gy.ConclusionsWe concluded that secondary neutron portion was higher than other radiation. Then, we recommended more attention to neutrons in the radiation protection in linac based high energy radiotherapy.     

Incidence of radiation toxicity in cervical cancer and endometrial cancer patients treated with radiotherapy alone versus adjuvant radiotherapy

AimThe study was made to evaluate early and late toxicity in a diversified group of patients receiving definitive or adjuvant radiotherapy in terms of clinical diagnosis and treatment methods.BackgroundRadiotherapy is a standard way of treatment in cervical and endometrial cancer patients, both as definitive and adjuvant therapy. But every radiation treatment may be involved with toxicity.Materials and methodsA detailed analysis was performed of 263 patients with gynaecological cancer treated with definitive (90 patients with cervical cancer received radiochemotherapy or radiotherapy exclusively) and adjuvant radiotherapy (38 with cervical and 135 with endometrial cancer).ResultsAcute reactions were found in 51.3% and late reactions were found in 14.8% of patients. It was stated that early (p < 0.007) and late (p < 0.003) post radiation reaction appear more frequently in women treated with definitive than adjuvant radiotherapy. The analysis of the whole group revealed higher rate of toxicity, both early and late, in the gastrointestinal tract than in the urinary system (p < 0.004). Comparing the subgroups, it was found that intestinal reactions occurred more frequently in the definitive radiotherapy group than in the adjuvant one.The occurrence of side effects was associated with the prolongation of total irradiation time due to necessary interruptions of radiotherapy. The comparison of the subgroups showed that interruptions occurred more frequently in patients receiving definitive rather than adjuvant radiotherapy (17.7–2.9%).ConclusionsDefinitive radiotherapy compared with adjuvant treatment may by associated with higher percentage of side effects caused by dose of therapy and correlation with chemotherapy.     

Influence of ABCB1 genetic variants in breast cancer treatment outcomes

BackgroundTransportation of anticancer drugs such as anthracyclines across the membrane is regulated by P-glycoprotein encoded by the human multidrug resistance gene 1 (ABCB1). Polymorphisms in the ABCB1 gene (1236C > T, 2677G > T/A, 3435C > T) have been found to be associated with intrinsic and acquired cross resistance to these anticancer drugs. Therefore, the aim of this study is to evaluate the influence of ABCB1 gene polymorphisms in breast cancer treatment outcomes in terms of response and toxicity.MethodResponse to neo-adjuvant chemotherapy was evaluated in 100 patients while grade 2–4 toxicity was followed in 207 patients, who had undergone FEC/FAC chemotherapy. Genotyping for ABCB1 polymorphisms was done by PCR-RFLP. Chi square and logistic regression analyses were used to calculate Odd's ratio using SPSS ver 17.0. A meta analysis was also performed using Comprehensive Meta Analysis Ver 2.ResultsIn response evaluation, 1236C > T polymorphism was significantly associated with treatment response for CT genotype [OR = 5.17(1.3–20.2), P = 0.018] and in dominant model (CC vs CT + TT) [OR = 4.63(1.25–17.0), P = 0.021]. In the toxicity group, the T allele of 1236C>T was associated with grade 2–4 tocxicity [OR 1.48(1.00–2.20), P = 0.049] and the association was also significant in the recessive model [OR 1.88(1.05–3.39), P = 0.033]. For other two SNPs 2677G>T/A and 3435C>T no association was seen with either treatment response or grade 2–4 toxicity. In meta analysis, no overall association was found.ConclusionIn our study, significant association was seen for ABCB1 1236C>T polymorphism with treatment response. The meta analysis did not show overall association with treatment outcomes.     

Results of combined radiotherapy and hormonal treatment of prostate cancer patients with initial PSA value >40 ng/ml

AimTo evaluate the outcome of prostate cancer patients with initial PSA value >40 ng/ml.BackgroundThe outcome of prostate cancer patients with very high initial PSA value is not known and patients are frequently treated with palliative intent. We analyzed the outcome of radical combined hormonal treatment and radiotherapy in prostate cancer patients with initial PSA value >40 ng/ml.MethodsBetween January 2003 and December 2007 we treated, with curative intent, 56 patients with non-metastatic prostate cancer and initial PSA value >40 ng/ml. The treatment consisted of two months of neoadjuvant hormonal treatment (LHRH analog), radical radiotherapy (68–78 Gy, conformal technique) and an optional two-year adjuvant hormonal treatment.ResultsThe median time of follow up was 61 months. 5-Year overall survival was 90%. 5-Year biochemical disease free survival was 62%. T stage, Gleason score, PSA value, and radiotherapy dose did not significantly influence the outcome. Late genitourinal and gastrointestinal toxicity was acceptable.ConclusionRadical treatment in combination with hormonal treatment and radiotherapy can be recommended for this subgroup of prostate cancer patients with good performance status and life expectancy.     

Implementation of a dose–response curve for γ-radiation in the Portuguese population by use of the chromosomal aberration assay

An in vitro dose–response curve following exposure to γ-radiation was determined at the IST/ITN, by use of the chromosomal aberration assay. This is the first study of this kind carried out among the Portuguese population. Un-irradiated and γ-irradiated peripheral blood lymphocytes from 16 healthy donors were cultured. A total of 22,395 metaphases were analyzed for frequency and distribution of dicentrics and centric rings, as a function of the radiation dose. The dose–response data for dicentrics and dicentrics plus centric rings were fitted by use of a linear–quadratic model: Y_dic = (0.0011 ± 0.0006) + (0.0105 ± 0.0035)D + (0.0480 ± 0.0019)D² and Y_{dic + rings} = (0.0011 ± 0.0006) + (0.0095 ± 0.0036)D + (0.0536 ± 0.0020)D². Also, calibration curves related to age and gender were determined, but no significant differences were found. Following the establishment of the dose–response curves, a validation experiment was carried out with three individuals. Real and estimated doses, obtained with the dose–response curves, were in agreement. These results give us confidence to apply both dose–response calibration curves in future biological dosimetry requirements.     

Radiation dose comparison between V/P-SPECT and CT-angiography in the diagnosis of pulmonary embolism

PurposeThe aim of this study is to compare two routine protocols at our institution, CTPA and V/P-SPECT, in terms of radiation dose to the most exposed organs (lungs and breast) and to the embryo/fetus in the case of pregnant patients.MethodsAt our institution, the CTPA protocol includes a contrast enhanced CT (scan parameters: 100 kVp, 700 mA, 0.5 s/rot, pitch 0.984) and in some cases a non-contrast enhanced CT acquisition (120 kVp, 400 mA, 0.5 s/rot, pitch 1.375).In the V/P-SPECT protocol, ventilation SPECT was performed after inhalation of 99mTc-Technegas, reaching 30 MBq in the lungs; perfusion was performed after intravenous administration of 60–120 MBq of 99mTc-MAA.The absorbed doses (mGy) to lungs and breast from CTPA were estimated using the “ImPACT CT Patient Dosimetry Calculator”. The embryo/fetus dose was estimated for different gestational stages (0–7, 8–12, 13–25 and 26–40 weeks) using the web based calculation tool “COnceptus Dose Estimation” (CODE).Doses to organs and embryo/fetus from V/P-SPECT were estimated based on published dose data normalized to administered activity (mGy/MBq).ResultsEmbryo/fetus absorbed doses are similar for CTPA and V/P-SPECT and bellow 1 mGy. The calculated dose to the lungs (breast) was 1.3–10.6 (27–136) times higher from CTPA when compared with V/P-SPECT.ConclusionFor the diagnosis of PE in women, if both imaging modalities are available, it is recommended to proceed with V/P-SPECT rather than CTPA due to the considerably lower radiation dose to the breast.     

Associations between oral hygiene habits,diet, tobacco and alcohol and risk of oral cancer: A case–control study from India

ObjectiveThis study examines the association between the incidence of oral cancer in India and oral hygiene habits, diet, chewing and smoking tobacco, and drinking alcohol. We also assessed the effects of oral hygiene habits with oral cancer risk among chewers versus never chewers.MethodsA hospital-based case–control study was conducted in Pune, India, based on face-to-face interviews, anthropometry, and intra-oral examinations conducted for 187 oral cancer cases and 240 controls.ResultsPoor oral hygiene score was associated with a significant risk of oral cancer (adjusted OR = 6.98; 95%CI 3.72–13.05). When stratified by tobacco-chewing habit, the poor oral hygiene score was a significant risk factor only among ever tobacco chewers (adjusted OR = 14.74; 95%CI 6.49–33.46) compared with never chewers (adjusted OR = 0.71; 95%CI 0.14–3.63). Dental check-ups only at the time of pain by ever-chewers with poor oral hygiene was associated with an elevated risk (adjusted OR = 4.22; 95%CI 2.44–7.29), while consumption of green, yellow, and cruciferous vegetables and citrus fruits was protective. A linear dose–response association was observed between oral cancer and chewing tobacco in terms of age at initiation, duration, and frequency of chewing per day (P < 0.001). Smoking more than 10 bidis/cigarettes per day (adjusted OR = 2.74; 95%CI 1.28–5.89) and for a duration >25 years (adjusted OR = 2.31; 95%CI 1.14–4.71) elevated the risk of oral cancer.ConclusionGood oral hygiene habits – as characterized by healthy gums, brushing more than once daily, use of toothpaste, annual dental check-ups, and a minimal number of missing teeth – can reduce the risk of oral cancer significantly. In addition to refraining from chewing/smoking tobacco, a diet adequate in fruits and vegetables may protect against the disease.     

Voluntary breath-hold reduces dose to organs at risk in radiotherapy of left-sided breast cancer

AimTo compare the dose to organs at risk with free breathing (FB) or voluntary breath-hold (VBH) during radiotherapy of patients with left sided breast cancer.BackgroundRadiotherapy reduces the risk of breast-cancer-specific mortality but the effects on other organs increase non-cancer-specific mortality. Radiation exposure to the heart, in particular in patients with left sided breast cancer, can be reduced by breath hold methods that increase the distance between the heart and the radiation field.Materials and MethodsThree-dimensional conformal radiotherapy (3D-CRT) dose plans for the left breast and organs at risk including the heart, left anterior descending coronary artery (LAD) and ipsilateral lung were compared with FB and VBH in ten patients with left sided breast cancer.ResultsThe mean doses to the heart and LAD were reduced by 50.4 % (p < 0.001) and 58.8 % (p = 0.006), respectively, in VBH relative to FB. The mean dose to the ipsilateral lung was reduced by 13.8 % (p = 0.11) in VBH relative to FB. The planning target volume (PTV) coverage was at least 95 % in both FB and VBH (p = 0.78).ConclusionThe VBH technique significantly reduces the dose to organs at risk in 3D-CRT treatment plans of left sided breast cancer.     

Prolonged breastfeeding reduces risk of breast cancer in Sri Lankan women: A case–control study

Goal: To assess the association between duration of breastfeeding and the risk of breast cancer in Sri Lankan women. Methods: We conducted a case–control study in women aged 30–64 years in selected health care facilities in the Western province. A total of 100 recent cases of breast cancer (histologically confirmed) and 203 controls (age and parity matched) were included. Detailed information regarding breastfeeding, menstruation, reproductive factors, passive smoking and other confounders was collected using a structured questionnaire. Adjusted odds ratios and 95% confidence intervals were calculated using multiple logistic regressions. Principle results: Multivariate analysis found that those women who breastfed for ≥24 months during lifetime had significantly lower risk of breast cancer than those who breastfed for less than 24 months (OR = 0.40; 95%CI = 0.22, 0.73). Compared to 0–11 months of lifetime breastfeeding, there was a 66.3% reduction in breast cancer risk in women who breastfed for 12–23 months, 87.4% reduction in 24–35 months and 94% reduction in 36–47 months categories. The mean duration of breastfeeding per child for ≥12 months was also associated with reduced risk of breast cancer (OR = 0.52; 95%CI = 0.28, 0.94). The significant factors associated with increased risk of breast cancer were: post-menopausal women (OR = 1.74; 95%CI = 1.01, 3.01); having an abortion in the past (OR = 3.42; 95%CI = 1.75, 6.66) and exposure to passive smoking (OR = 2.96, 95%CI = 1.53, 5.75). Major conclusions: Prolonged breastfeeding significantly reduces the risk of breast cancer and this protective effect was supported by a dose–response relationship. Risk due to passive smoking should be emphasized in anti-smoking programmes.     

Removal of Cu(II) ions by biosorption onto powdered waste sludge (PWS) prior to biological treatment in an activated sludge unit: A statistical design approach

Biological treatment of synthetic wastewater containing Cu(II) ions was realized in an activated sludge unit with pre-adsorption of Cu(II) onto powdered waste sludge (PWS). Box-Behnken experimental design method was used to investigate Cu(II), chemical oxygen demand (COD) and toxicity removal performance of the activated sludge unit under different operating conditions. The independent variables were the solids retention time (SRT, 5–30 d), hydraulic residence time (HRT, 5–25 h), feed Cu(II) concentration (0–50 mg L^?1) and PWS loading rate (0–4 g h^?1) while percent Cu(II), COD, toxicity (TOX) removals and the sludge volume index (SVI) were the objective functions. The data were correlated with a quadratic response function (R² = 0.99). Cu(II), COD and toxicity removals increased with increasing PWS loading rate and SRT while decreasing with the increasing feed Cu(II) concentration and HRT. Optimum conditions resulting in maximum Cu(II), COD, toxicity removals and SVI values were found to be SRT of 30 d, HRT 15 h, PWS loading rate 3 g h^?1 and feed Cu(II) concentration of less than 30 mg L^?1.