Radiation Therapy Oncology Group Score Research Articles

Mometasone Furoate Cream Reduces Acute Radiation Dermatitis in Patients Receiving Breast Radiation Therapy: Results of a Randomized Trial

We wanted to confirm the benefit of mometasone furoate (MF) in preventing acute radiation reactions, as shown in a previous study (Boström et al, Radiother Oncol 2001;59:257-265). The study was a double-blind comparison of MF with D (Diprobase), administered daily from the start of radiation therapy for 5 weeks in patients receiving breast radiation therapy, 40 Gy in 2.67-Gy fractions daily over 3 weeks. The primary endpoint was mean modified Radiation Therapy Oncology Group (RTOG) score. Mean RTOG scores were significantly less for MF than for D (P=.046). Maximum RTOG and mean erythema scores were significantly less for MF than for D (P=.018 and P=.012, respectively). The Dermatology Life Quality Index (DLQI) score was significantly less for MF than for D at weeks 4 and 5 when corrected for Hospital Anxiety and Depression (HAD) questionnaire scores. MF cream significantly reduces radiation dermatitis when applied to the breast during and after radiation therapy. For the first time, we have shown a significantly beneficial effect on quality of life using a validated instrument (DLQI), for a topical steroid cream. We believe that application of this cream should be the standard of care where radiation dermatitis is expected.

Topical application of a sandal wood oil and turmeric based cream prevents radiodermatitis in head and neck cancer patients undergoing external beam radiotherapy: a pilot study

The study objective was to assess the effectiveness of a turmeric- and sandal wood oil-containing cream [Vicco(®) turmeric cream (VTC); Vicco Laboratories, Parel, India] on radiodermatitis in patients with head and neck cancer undergoing radiotherapy. A total of 50 patients with head and neck cancer requiring >60 Gy of curative radiotherapy/chemoradiotherapy were enrolled in the study. The volunteers were randomly divided into two groups of 25 patients. Group 1 was assigned to a topical application of Johnson's(®) baby oil (Johnson & Johnson Ltd, Baddi, India) and Group 2 for VTC. Prophylactic application of the cream was initiated on Day 1 and continued every day until 2 weeks after the end of treatment. Both agents were symmetrically applied within the irradiated field five times a day, and the acute skin reactions were assessed twice weekly in accordance with the Radiation Therapy Oncology Group scores by an investigator who was unaware of the details. The incidence of radiodermatitis increased with the exposure to radiation and was the highest in both groups at Week 7. However, a significant reduction in grades of dermatitis were seen in cohorts applying VTC at all time points, including 2 weeks post radiotherapy (p < 0.015 to p < 0.001). The occurrence of Grade 3 dermatitis was lower in the cohorts using VTC and was statistically significant (p < 0.01). Additionally, follow-up observations 2 weeks after the completion of radiotherapy also showed a reduced degree of radiodermatitis in cohorts applying VTC, which was significant (p = 0.015). VTC is shown to be effective in preventing radiodermatitis and needs to be validated in larger double-blind trials. For the first time, this study shows that the turmeric- and sandal oil-based cream was effective in preventing radiation-induced dermatitis.

Hypofractionated External Beam Radiotherapy to Boost the Prostate with ≥85 Gy/Equivalent Dose for Patients with Localised Disease at High Risk of Lymph Node Involvement: Feasibility, Tolerance and Outcome

AimsTo evaluate the tolerance and preliminary outcome of prostate cancer patients at high risk of lymph node involvement treated with normofractionated whole pelvic radiotherapy (WPRT) followed by a hypofractionated boost to the prostate with an intensity-modulated radiotherapy (IMRT) technique. Materials and methodsBetween 2004 and 2011, 78 T1-4N0M0 prostate cancer patients at high risk of lymph node involvement (70 patients with a Roach index ≥ 15%; 57 with T-stage ≥ 3a; 40 with Gleason score ≥ 8) underwent WPRT to a median normofractionated dose of 50.4 Gy (range 48.0–50.4 Gy) with conformal three-dimensional techniques for most patients. A 24 Gy boost (4 Gy/six fractions, twice weekly) was delivered to the prostate with IMRT. The total median delivered dose was 74.4 Gy, equivalent to 85.2 Gy in 2 Gy/fractions (α/β = 1.5 Gy). All patients underwent androgen deprivation for a total median time of 10.8 months. The maximum gastrointestinal and genitourinary acute and late toxicity scores were recorded according to the Radiation Therapy Oncology Group scoring system. ResultsAll patients completed treatment as planned. Only 1% of patients presented with grade 3 genitourinary or gastrointestinal acute toxicity and none scored ≥ grade 4. With a median follow-up of 57 months, the 5 year probability of late grade ≥2 genitourinary and gastrointestinal toxicity-free survival was 79.1 ± 4.8% and 84.1 ± 4.5%, respectively. The 5 year biochemical disease-free survival, local relapse-free survival and distant metastasis-free survival were 84.5 ± 4.5%, 96.0 ± 2.8% and 86.4 ± 4.4%, respectively. A pre-radiotherapy prostate-specific antigen ≤0.3 ng/ml was associated with a better 5 year biochemical disease-free survival (P = 0.036) and distant metastasis-free survival (P = 0.049). ConclusionsThe use of a hypofractionated IMRT boost after WPRT may allow a minimally invasive dose escalation to successfully treat patients with non-metastatic prostate cancer at high risk of lymph node involvement. Higher prostate-specific antigen values before radiotherapy may require alternative adjuvant treatments to further optimise the outcome of this high-risk group of patients.

Oral Glutamine Reduces Radiation Morbidity in Breast Conservation Surgery

This study examined the effect of oral glutamine (Gln) on radiation injury in breast cancer patients undergoing radiation therapy. The radiation injury was evaluated using Radiation Therapy Oncology Group (RTOG) scales. Cosmesis was scored. Blood Gln and glutathione (GSH) levels were determined. Serum protein profiling was determined using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS). Patients receiving Gln scored significantly better in RTOG score than the patients receiving placebo. Cosmetic scores averaged excellent in the Gln group vs fair to good in the placebo group. Blood Gln and GSH levels were significantly higher in the Gln group vs the placebo group. Serum protein profiling with SELDI-TOF MS identified a novel Gln-responsive protein that showed amino acid similarity with myoglobin. These results suggest that Gln is an effective way to reduce radiation morbidity to breast cancer and is associated with the increased expression of a novel serum protein biomarker.

Investigation of Genetic Polymorphisms Related to the Outcome of Radiotherapy for Prostate Cancer Patients

The purpose of this study was to evaluate the association between ATM, TP53 and MDM2 polymorphisms in prostate cancer patients and morbidity after radiotherapy. The presence of ATM (rs1801516), TP53 (rs1042522, rs1800371, rs17878362, rs17883323, and rs35117667), and MDM2 (rs2279744) polymorphisms was assessed by direct sequencing of PCR fragments from 48 patients with histologically proven prostate adenocarcinoma and treated with external beam radiation. The side effects were classified according to the Radiation Therapy Oncology Group (RTOG) score. The results showed no association between clinical characteristics and the development of radiation toxicities (P > 0.05). The C>T transition in the position 16273 (intron 3) of TP53 (rs35117667) was significantly associated with the risk of acute skin toxicity (OR: 0.0072, 95% CI 0.0002–0.227, P = 0.003). The intronic TP53 polymorphism at position 16250 (rs17883323) was associated with chronic urinary toxicity (OR: 0.071, 95%CI 0.006–0.784, P = 0.032). No significant associations were found for the remaining polymorphisms (P > 0.05). The results show that clinical characteristics were not determinant on the developing of radiation sensitivity in prostate cancer patients, and intronic TP53 polymorphisms would be associated with increased acute and chronic radiation toxicities. These observations corroborate the importance of investigating the genetic profile to predict adverse side effects in patients undergoing radiotherapy.

Efficacy of Radiofrequency Coagulation in Managing Chronic Radiation Proctitis

Purpose: Radiation therapy is a modality frequently utilized to manage pelvic malignancies from a primary, post-operative adjuvant, or palliative approach. Despite the high prevalence of post treatment chronic radiation proctitis (CRP), medical management is not clearly defined or standardized. The purpose of our study was to evaluate the feasibility of radiofrequency energy (RFE) in treating CRP compared to that of the traditional coagulation modality of argon plasma coagulation (APC). Methods: We performed a prospective randomized study comparing standard APC and RFE in patients with symptomatic CRP and their effect on common outcomes. Patients enrolled in the study had pelvic malignancy treated with radiotherapy and subsequent history of chronic radiation proctitis (defined as development of proctitis at least 90 days from end of radiation treatment). Proctitis was scored based on RTOG (Radiation Therapy Oncology Group) and Vienna endoscopic scoring system. Primary study endpoint was reduction or absence of bleeding episodes requiring no further endoscopic treatment after 6 months. Secondary endpoints included time to resolution of symptoms, and need for further blood transfusions. Independent Student T-test was utilized to compare mean primary and secondary endpoints. P-value of 0.05 was considered statistically significant. Results: To date, a total of 7 patients have been assigned to either RFE (n=4), or APC (n=3) group. Mean patient age for both groups was 76.7 years (64 to 83; SD: 5.94). Average amount of prior radiation dose used in treatments for pelvic malignancy in the RFE group was not significantly different from APC group. Average baseline frequency of bleeds/week in the RFE group (M = 6.5 times/week; SD: 3.3) were not significantly different than the APC group (M = 3.67 times/week; SD: 2.9). Baseline RTOG scores in the RFE (M = 1.5; SD: 0.6) group were not significantly different from the APC (M = 1.3; SD: 0.6) group (p = 0.58). The frequency of bleeds at first follow up were significantly higher for the RFE (M = 4.3 times/week; SD: 3.4) group than the APC (M = 0.3 times/week; SD: 0.6), p = 0.025. Mean RTOG score at second follow up visit was higher for RFE group (M = 1.5; SD: 0.91) than it was for the APC group (M = 1.0; SD: 0), p = 0.007. There was no difference in RTOG scores at third follow up visit for RFE group (M = 1.33; SD: 0.6) and APC group (M = 0.2 SD: 0.70), p = 0.72. Conclusion: While the APC group appears to have better control over limiting frequency of bleeding, RFE may control CRP bleeding as efficaciously as APC in terms of reducing patient symptom severity, time to resolution of bleeding, and need for blood transfusions. Further larger longitudinal studies are needed to confirm these findings.

Hypofractionated helical tomotherapy using 2.5–2.6 Gy daily fractions for localized prostate cancer

The purpose of this study is to evaluate the tolerability of hypofractionated helical tomotherapy (HT) in the treatment of localized prostate cancer. We evaluated 48 patients with primary adenocarcinoma of the prostate (cT1-T3N0M0) who were treated with hypofractionated HT from August 2008 through July 2011. Hypofractionated regimens included: 68.04Gy at 2.52Gy/fraction, 70Gy at 2.5Gy/fraction, and 70.2Gy at 2.6Gy/fraction. Genitourinary (GU) and gastrointestinal (GI) toxicity was scored using the Radiation Therapy Oncology Group scoring system. Thirty-two patients were treated with 68.04Gy, 5 patients with 70Gy, and 11 with 70.2Gy. The median age at diagnosis was 69years (range 49-87) and the median follow-up 11months (range 7-40). Grade 2 acute GI toxicity occurred in 9 patients (19%). No grade 3 or higher acute GI toxicity was observed. Grade 2 and 3 acute GU toxicities occurred in 19 and 6% of patients, respectively. The incidence of late grade 2 GI and GU toxicity was 4 and 2%, respectively. No grade 3 or higher late toxicities were observed. Multivariate analysis showed that patients treated at 2.6Gy/fraction or those who received a total radiation dose ≥70Gy had higher rates of grade ≥2 acute GU toxicity (P=0.004 and P=0.048, respectively). Hypofractionated HT in the treatment of localized prostate cancer is well tolerated with no grade 3 or higher early or late GI and GU toxicities. Further research is needed to assess definitive late toxicity and tumor control.

Association of single nucleotide polymorphisms in the genes ATM, GSTP1, SOD2, TGFB1, XPD and XRCC1 with risk of severe erythema after breast conserving radiotherapy

PurposeTo examine the association of polymorphisms in ATM (codon 158), GSTP1 (codon 105), SOD2 (codon 16), TGFB1 (position −509), XPD (codon 751), and XRCC1 (codon 399) with the risk of severe erythema after breast conserving radiotherapy.Methods and materialsRetrospective analysis of 83 breast cancer patients treated with breast conserving radiotherapy. A total dose of 50.4 Gy was administered, applying 1.8 Gy/fraction within 42 days. Erythema was evaluated according to the Radiation Therapy Oncology Group (RTOG) score. DNA was extracted from blood samples and polymorphisms were determined using either the Polymerase Chain Reaction based Restriction-Fragment-Length-Polymorphism (PCR-RFL) technique or Matrix-Assisted-Laser-Desorption/Ionization –Time-Of-Flight-Mass-Spectrometry (MALDI-TOF). Relative excess heterozygosity (REH) was investigated to check compatibility of genotype frequencies with Hardy-Weinberg equilibrium (HWE). In addition, p-values from the standard exact HWE lack of fit test were calculated using 100,000 permutations. HWE analyses were performed using R.ResultsFifty-six percent (46/83) of all patients developed erythema of grade 2 or 3, with this risk being higher for patients with large breast volume (odds ratio, OR = 2.55, 95% confidence interval, CI: 1.03–6.31, p = 0.041). No significant association between SNPs and risk of erythema was found when all patients were considered. However, in patients with small breast volume the TGFB1 SNP was associated with erythema (p = 0.028), whereas the SNP in XPD showed an association in patients with large breast volume (p = 0.046). A risk score based on all risk alleles was neither significant in all patients nor in patients with small or large breast volume. Risk alleles of most SNPs were different compared to a previously identified risk profile for fibrosis.ConclusionsThe genetic risk profile for erythema appears to be different for patients with small and larger breast volume. This risk profile seems to be specific for erythema as compared to a risk profile for fibrosis.

A Feasibility Study of Neo-Adjuvant Low-Dose Fractionated Radiotherapy with Two Different Concurrent Anthracycline-Docetaxel Schedules in Stage IIA/B-IIIA Breast Cancer

The aim of the study was to evaluate the feasibility of neoadjuvant low-dose fractionated radiotherapy, in combination with two anthracycline-docetaxel regimens, in breast cancer treatment. Women with stage IIA/B-IIIA breast cancer were assigned to receive the treatment of low-dose fractionated radiotherapy (0.4 Gy/per fraction, 2 fractions per day, for 2 days, every 21 days for 8-6 cycles) with concomitant neoadjuvant chemotherapy with non-pegylated liposomal doxorubicin and docetaxel. Two chemotherapy schedules were planned to be combined with low-dose fractionated radiotherapy. The first schedule consisted of four cycles of non-pegylated liposomal doxorubicin sequentially followed by four cycles of docetaxel, and the second schedule consisted of six cycles of non-pegylated liposomal doxorubicin plus concomitant docetaxel. Acute toxicity was evaluated according to the Radiation Therapy Oncology Group score system. Pathological response was evaluated by the Mandard score and expressed as tumor regression grade. Between March 2008 and February 2009, 10 patients underwent low-dose fractionated radiotherapy and concomitant chemotherapy. No grade 3-4 breast toxicity was observed. Five patients had a clinical complete response. Seven patients underwent conservative surgery. Overall, tumor regression grade 1 (absence of residual cancer) was achieved in one patient (10%) and grade 2 (residual isolated cells scattered through the fibrosis) in 4 patients (40%). The pathologic major response rate (tumor regression grade 1 + 2) was 20% in patients receiving low-dose fractionated radiotherapy and sequential non-pegylated liposomal doxorubicin and docetaxel and 80% in the group receiving low-dose fractionated radiotherapy and concurrent non-pegylated liposomal doxorubicin and docetaxel treatment. Concomitant low-dose fractionated radiotherapy combined with anthracycline and docetaxel is feasible. The toxicity profile of radio-chemotherapy was similar to that of chemotherapy alone: there was no acute skin or cardiac toxicity. The concurrent application of liposomal doxorubicin and docetaxel with low-dose fractionated radiation led to higher histological response rates compared to the sequential application of the same two drugs.

Long-Term Outcomes of Early-Stage Nasopharyngeal Carcinoma Patients Treated With Intensity-Modulated Radiotherapy Alone

Reports of intensity-modulated radiotherapy (IMRT) for early-stage nasopharyngeal carcinoma (NPC) have been limited. The present study evaluated the long-term survival outcomes and toxicity of early-stage NPC patients treated with IMRT alone. Between February 2001 and January 2008, 198 early-stage (T1-T2bN0-N1M0) NPC patients had undergone IMRT alone. The data from these patients were retrospectively analyzed. The patients were treated to 68 Gy at 2.27 Gy/fraction prescribed to the planning target volume of the primary nasopharygeal gross tumor volume. The Radiation Therapy Oncology Group scoring system was used to assess the toxicity. At a median follow-up of 50.9 months (range, 12-104), the 5-year estimated disease-specific survival, local recurrence-free survival, and distant metastasis-free survival rate was 97.3%, 97.7%, and 97.8%, respectively. The 5-year local recurrence-free survival rate was 100% for those with Stage T1 and T2a and 94.2% for those with Stage T2b lesions (p = 0.252). The 5-year distant metastasis-free survival rate for Stage T1N0, T2N0, T1N1, and T2N1 patients was 100%, 98.8%, 100%, and 93.8%, respectively (p = .073). All local recurrence occurred in patients with T2b lesions. Five patients developed distant metastasis. Of these 5 patients, 4 had had Stage T2bN1 disease and 1 had had Stage T2bN0 disease with retropharyngeal lymph node involvement. The most common acute toxicities were mainly Grade 1 or 2. At 24 months after IMRT, no Grade 3 or 4 xerostomia had developed, and 62 (96.9%) of 64 evaluated patients were free of trismus; only 2 patients (3.1%) had Grade 1 trismus. Radiation encephalopathy and cranial nerve injury were not observed. IMRT alone for Stage T1N0, T2N0, T1N1, and T2N1 yielded satisfactory survival outcomes with acceptable toxicity, and no differences were found in survival outcomes among these four subgroups. Patients with Stage T2b lesions might have relatively greater risk of local recurrence and those with T2bN1 disease mighth have a greater risk of distant metastasis.

Radiation-Induced Bowel Complications: Laparoscopic Versus Open Staging of Gynecologic Malignancy

To evaluate whether the type of surgical approach used to stage gynecologic malignancies influences the risk of developing nonrectal radiation-induced intestinal injury (NRRIII) in patients who subsequently receive adjuvant radiotherapy. A prospectively entered database was queried for all women with either primary or recurrent gynecologic malignancy who underwent external-beam radiation therapy±brachytherapy and who had prior abdominopelvic surgery at our institution. Univariate and multivariate analysis of variables potentially affecting the risk of developing significant bowel toxicity (defined as grade 2 or more according to Radiation Therapy Oncology Group scoring) were performed. One hundred fifty-nine patients were identified. The site of primary tumor was the cervix in 61(38%) patients and the corpus uteri in the remaining patients (98, 62%). Treatment was delivered with a combination of external-beam and intracavitary irradiation to 50 (31.4%) patients, and 109 (68.6%) patients received only external-beam irradiation. Staging procedures were performed by open surgery in 93 (58.5%) patients, whereas laparoscopy was the surgical approach of choice in 66 (41.5%) women. Fifteen patients (9.4%) developed grade 2 or greater NRRIII, at median latency of 10months (range 3-64months); six were diagnosed as grade 3 complications requiring surgery, and three developed grade 4 complication. Multiple regression revealed an independent protective effect of pretreatment laparoscopic staging against the risk of developing both grade ≥2 and grade ≥3 NRRIII. Notwithstanding potential limitations of nonrandomized study design, our findings suggest that the benefits of minimal-access surgery used to perform staging procedures may translate into long-term reduction in radiation-induced bowel injury.

Three or Four Fractions of 4–5 Gy per Week in Postoperative High-Dose-Rate Brachytherapy for Endometrial Carcinoma

To evaluate the results of high-dose-rate brachytherapy (HDRBT) using a schedule of three or four fractions per week, when possible, in 89 patients on local control and toxicity in postoperative treatment of endometrial carcinoma. The effect of the overall HDRBT treatment time (OTT) on toxicity was also evaluated. Fédération Internationale de Gynécologie Obstétrique Stage: 24 IB, 45 IC, 4 IIA, 6 IIB, 4 IIIA, 2 IIIB, and 4 IIIC. Radiotherapy: Group 1-67 of 89 patients received external beam irradiation (EBI; 44-50 Gy) plus HDRBT (3 fractions of 4-6 Gy); Group 2-22 of 89 patients received HDRBT alone (6 fractions of 4-5 Gy). OTT: Group 1-HDRBT was completed in a median of 5 days in 32 patients and in >5 days in 35; Group 2-HDRBT was completed in <15 days in 11 patients and in ≥16 days in 11. Toxicity was evaluated using Radiation Therapy Oncology Group scores and the bioequivalent dose (BED) study was performed in vaginal mucosa surface. Statistics included Student's t test, chi-square test, and receiving operator curves. With a mean follow-up of 31 months (range, 6-70), 1 of 89 patients had vaginal relapse. Early toxicity appeared in 8 of 89 (9%) patients and was resolved. Late toxicity appeared in 13/89 (14%): vaginal nine Grade 1, three Grade 2, one Grade 4; bladder two Grade 2; rectal three Grade 1, one Grade 2. No differences were found in relation to OTT in Groups 1 and 2. Mean BED was 88.48 Gy in Group 1 and 165.28 Gy in Group 2. Cases with Grade 2 late vaginal toxicity received >75 Gy after EBI and >165 Gy in Group 2. Three fractions of 4-5 Gy in 3-5 days after EBI or 6 fractions in <15 days in patients receiving HDRBT alone was a safe treatment in relation to toxicity and local control. Vaginal surface BED less than 75 Gy after EBI and less than 160 Gy in HDRBT alone may be safe to avoid G2 toxicity.

Quality of radiosurgery for single brain metastases with respect to treatment technology: a matched-pair analysis

A comparison of treatment parameters and quality of clinical outcome in patients with single brain metastases treated with two different technologies for radiosurgery (Gamma Knife and CyberKnife). Treatment parameters were statistically analyzed. Clinical outcome was assessed by matched-pair analysis based on the treatment device, differences in dose prescription, and the date of the treatment. Patients were matched according to their tumor size, age, gender, primary cancer, and Radiation Therapy Oncology Group score. Survival post-radiosurgery, local and distant tumor control, and complications were analyzed. Predictive factors were investigated. 423 single brain metastases were treated with Gamma Knife and 73 with CyberKnife. Tumor volumes were similar. The parameters minimum tumor dose, maximum tumor dose, prescription isodose volume, conformality index, homogeneity index, volume of tissue receiving a dose of 10 Gy or more were significantly larger in Gamma Knife group. Sixty-three patients were good matches. These showed the same pattern in parameters. Concerning the outcome analysis, only overall survival differed significantly between groups, twice as long with CyberKnife (P < 0.03). According to pooled data, dose was predictive of local failure, whole brain radiation therapy and chemotherapy were predictive of toxicity, the Radiation Therapy Oncology Group score was predictive of survival after radiosurgery, and date of treatment was predictive of overall survival. No factor predicted new brain metastases, including whole brain radiation therapy. The most important result of this study was the finding that the obvious differences in treatment-related parameters between Gamma Knife and CyberKnife had no impact on the quality of the clinical outcome after radiosurgery. Survival time increased chronologically, presumably due to an intensified anti-cancer therapy in the more recent era of the CyberKnife treatments.

Leptomeningeal carcinomatosis

Leptomeningeal carcinomatosis (LC) represents a devastating complication of systemic cancer, and patients with LC have a dismal prognosis and increased mortality. The few studies that have focused on the evaluation of prognostic factors in patients with LC have resulted in contradictory results. Thus, the treatment of LC remains controversial, and no straightforward guidelines exist in the literature. The objective of the current study was to identify prognostic markers related to LC survival to better select patients who are eligible for intensive treatment. Seventy patients who had a diagnosis of LC were reviewed, and clinical data, cerebrospinal fluid (CSF) parameters, tumor-related characteristics, and treatment information were registered. The impact of single parameters on overall survival was determined by both univariate and multivariate analyses. The multivariate analysis revealed that Radiation Therapy Oncology Group score<or=2 (P=.028), a glucose level in CSF>or=2.7 mmol/L (P=.001), the presence of infratentorial symptoms at onset (P=.026), and intrathecal treatment (P<.001) were associated independently with longer overall survival in patients with LC. In addition, the same clinical factors also predicted response to treatment in such patients. The predictive factors for patients with LC that were identified in this study could help to better select patients who are more likely to benefit from chemotherapy.

Evaluation of Different Score Index for Predicting Prognosis in Gamma Knife Radiosurgical Treatment for Brain Metastasis

To assess the utility of the Radiation Therapy Oncology Group Recursive Partitioning Analysis (RPA) and Score Index for Radiosurgery (SIR) stratification systems in predicting survival in patients with brain metastasis treated with Gamma Knife radiosurgery (GKRS). A total of 185 patients were included in the study. Patients were stratified according to RPA and SIR classes. The RPA and SIR classes, age, Karnofsky Performance Status (KPS), and systemic disease were correlated with survival. Five patients were lost to follow-up. Median survival in patients in RPA Class 1 (30 patients) was 17 months; in Class 2 (140 patients), 10 months; and in Class 3 (10 patients), 3 months. Median survival in patients in SIR Class 1 (30 patients) was 3 months; in Class 2 (135 patients), 8 months; and in Class 3 (15 patients), 20 months. In univariate testing, age younger than 65 years (p = 0.0004), KPS higher than 70 (p = 0.0001), RPA class (p = 0.0078), SIR class (p = 0.0002), and control of the primary tumor (p = 0.02) were significantly associated with improved outcome. In multivariate analysis, KPS (p < 0.0001), SIR class (p = 0.0008), and RPA class (p = 0.03) had statistical value. This study supports the use of GKRS as a single-treatment modality in this selected group of patients. Stratification systems are useful in the estimation of patient eligibility for GKRS. A second-line treatment was necessary in 30% of patients to achieve distal or local brain control. This strategy is useful to control brain metastasis in long-surviving patients.

Small bowel bacterial overgrowth and lactose intolerance during radical pelvic radiotherapy: An observational study

Introduction Loose stool affects up to 80% of all patients during pelvic radiotherapy and faecal incontinence may occur. Several causes for diarrhoea have been defined, though few oncologists target these causes in affected patients and most treat symptomatically only. It is not known whether small bowel bacterial overgrowth, a frequent cause of gastrointestinal symptoms in other contexts, occurs during radiotherapy. The frequency of new-onset lactose intolerance during pelvic radiotherapy is also not clear. Aims and methods To perform an observational pilot study to estimate the incidence of small bowel bacterial overgrowth and lactose intolerance during radical pelvic radiotherapy. Before treatment started and at weeks 4–5 of pelvic radiotherapy, a glucose hydrogen breath test and lactose tolerance test were performed. Gastrointestinal symptoms were assessed using the Vaizey incontinence questionnaire and the Radiation Therapy Oncology Group scoring system. Results Twenty two men and 17 women (median age 61, range 42–81) were recruited, four were treated for gastrointestinal, 17 were treated for gynaecological and 18 for urological cancers. Thirty-eight patients underwent glucose hydrogen breath tests and 26 patients underwent lactose breath tests at both time points. Ten patients (26%) were positive for the glucose hydrogen breath test: 60% of these developed new or worsening faecal incontinence during treatment and 60% had worsening bowel frequency. Four patients (15%) developed lactose intolerance. Of these 1 developed worsening faecal incontinence during treatment, 2 (50%) developed new-onset increase in bowel frequency or a change in the quality of bowel habit. Conclusion Small bowel bacterial overgrowth and lactose intolerance may occur during radical pelvic radiotherapy and are likely to contribute to gastrointestinal symptoms in some patients.

Concurrent chemoradiation for locally advanced squamous cell carcinoma of the vagina: case series and literature review

We reviewed our experience with patients with primary squamous cell carcinoma of the vagina who received concurrent chemoradiation therapy (CCRT). We retrospectively analyzed six patients (median age, 60 years) with squamous cell carcinoma of the vagina who underwent CCRT between 2002 and 2005 at the University of the Ryukyus Hospital. Two patients were in International Federation of Obstetricians and Gynecologists (FIGO) stage II, one in stage III, and three in stage IVA. All patients had an Eastern Cooperative Oncology Group (ECOG) performance status of 2 or less. Tumor size ranged from 3.2 to 7.7 cm. All patients were treated with true pelvic external-beam radiotherapy (EBRT) at 50 Gy. Then two of the six patients underwent intracavitary vaginal brachy-therapy. The remaining four patients received boost EBRT with shrinking fields. Total radiation dose to the vaginal tumor ranged from 60 to 66 Gy. All patients received two or three concomitant cycles of cisplatin during EBRT. All six patients completed their scheduled CCRT, and achieved a clinical complete response. One stage II patient died of disease 24 months after treatment, and the stage III patient had local failure at 12 months. The remaining four patients were free of their disease at 18, 23, 33, and 55 months, respectively. One patient with stage IVA developed a vesicovaginal fistula during CCRT. Nevertheless, CCRT was well tolerated by all six patients, and no grade 3 or 4 late toxicity was observed, as evaluated by the Radiation Therapy Oncology Group (RTOG) scoring system. CCRT is effective for primary squamous cell carcinoma of the vagina and should be considered for treatment in patients with high-risk disease having good performance status.

Salvage Radiotherapy After High-Intensity Focused Ultrasound for Localized Prostate Cancer: Early Clinical Results

To evaluate the first results of salvage radiotherapy after high-intensity focused ultrasound (HIFU) in terms of feasibility, tolerance, and oncologic control. From March 1995 to May 2004, 45 patients presenting with local failure after HIFU underwent salvage radiotherapy alone (n = 32) or combined with hormonal therapy (n = 13). The modalities of radiotherapy are described. Tolerance was evaluated using the Radiation Therapy Oncology Group score for urinary and digestive side effects, and incontinence was evaluated using the Ingelman Sundberg score. Patients answered a questionnaire. For the 32 patients who underwent radiotherapy alone, the oncologic early results were given by the disease-free survival rate, defined as no biochemical progression and no androgen suppression therapy. The median and mean follow-up were 40 and 46 months, respectively, for the whole series. No additional digestive or urinary toxicity developed with salvage radiotherapy after HIFU. The data from 32 patients were evaluated, with a median follow-up of 37 months after radiotherapy. The 5-year disease-free survival rate was 64% for the 32 patients evaluated. The 5-year disease-free survival rate reached 80% for patients treated for positive biopsy findings and was 44% for those with isolated biochemical failure. Salvage radiotherapy after HIFU for local recurrence is feasible, with no additional toxicity. The early oncologic results are encouraging when isolated local recurrence is proven but longer follow-up is needed.

A New Scoring System for Malignant Astrocytomas

Currently there are a few scoring systems for malignant astrocytoma, but they are not widely accepted. The aim of this study was to create a scoring system for supratentorial malignant astrocytoma, which could be used in both developed and developing societies. This study was performed in 128 patients who had supratentorial malignant astrocytoma (grade III or IV). They were operated, and after the operation patients were irradiated with 50-60 Gy. The mean age was 55.1 years. The mean Karnofsky performance status (KPS) was 51. The tumour removal >90% was achieved in 57.8%. A biopsy was never exclusively performed. The mean survival was 8.2 months and 12-month survival was 25%. Thirteen out of 35 data that we tested had a prognostic value for survival time. By using the most appropriate four parameters (age, KPS, initial seizure and histopathological grade) we created a scoring system - MAS (Malignant Astrocytoma Score). The scores range from 0-16. The area under the ROC (Receiver Operating Characteristic) curve showed that the AUC for the prediction of 6-, 12- and 18-month survival was 0.729, 0.755, and 0.927. We compared MAS with two of the most commonly used scoring systems. The AUC for the same prediction, using the MRC (Medical Research Council) was 0.673, 0.637, and 0.888. For the RTOG (Radiation Therapy Oncology Group) score the AUC was 0.672, 0.700, and 0.854. We are of the opinion that MAS represents a useful scoring system to determine the severity of the illness and make a prognosis for both individuals and groups of patients with malignant supratentorial astrocytoma. MAS is more accurate than predictions made by other systems currently in use; it includes prognostic factors that are widely accepted; it can be done at the patient's bedside and in clinics in developing societies.

Segmental Urethral Dosimetry and Urinary Toxicity in Patients With No Urinary Symptoms Before Permanent Prostate Brachytherapy

To determine whether segmental urethral dosimetry is predictive for the degree of urinary morbidity after prostate brachytherapy in patients with no urinary symptoms before prostate brachytherapy. Between May 2000 and November 2005, 1,107 patients underwent iodine-125 monotherapy with urethral sparing techniques. A total of 166 patients fulfilled the selection criteria: baseline (International Prostate Symptom Score) IPSS < or =5, no androgen deprivation therapy, and prostate ultrasound planning volumes (PUTV) <45 mL. The median follow-up was 44 months. Urinary morbidity was defined by maximum increase in IPSS, time to IPSS resolution, maximum Radiation Therapy Oncology Group (RTOG) score, time to RTOG resolution, and urinary retention. Surrogate deviated urethra was contoured and doses calculated at the base, mid-prostate, apex, and urogenital diaphragm. Univariate and multivariate analysis was used to evaluate urethral and prostate dosimetry, age, PUTV, and number of needles for their association with urinary morbidity. Urethral dose was fairly constant in all urethra segments except prostate base, where the variation in does was large. On multivariate analysis, higher urethral base D50, V100, and larger PUTV were predictive for higher maximum increase in IPSS. Higher urethral base V100 and larger PUTV predicted for prolonged IPSS resolution. Higher urethral base D50 and larger needle number predicted for longer RTOG resolution. Higher urethral base V100 predicted for RTOG > or =2 toxicity. Radiation dose to the urethral base, larger PUTV, and needle number, predicted for increased urinary toxicity after prostate brachytherapy. Correlation between urinary morbidity and urethral base dosimetry may reflect a large variation in urethral dose observed at the prostate base.