Months Of Radiotherapy Research Articles

Radiotherapy followed by adjuvant temozolomide treatment of malignant glioma

Background Malignant gliomas are the most frequent primary brain tumors in adults. In this clinical trial, we compared the therapeutic advantage of radiotherapy followed by temozolomide vs radiotherapy alone for the malignant glioma patients. Methods In the 4-year retrospective study, 31 patients with histologically confirmed malignant gliomas, in which 10 patients received radiotherapy followed by temozolomide (group A) and 21 patients received radiotherapy alone (group B). The main end point of evaluation and comparison of 2 therapeutic trials was overall survival. Results Two patients (6%) underwent biopsy, 19 patients (62%) underwent subtotal resection, and 10 patients (32%) underwent gross total resection. Mean overall survival was 30.44 ± 2.41 months for radiotherapy followed by adjuvant temozolomide vs 17.95 ± 4.27 months for radiotherapy alone ( P = .007). No major adverse effects were observed. Conclusions Based on our study, the patients of malignant glioma treated with radiotherapy followed by temozolomide obtained a statistically significant better benefit of survival than those treated with radiotherapy alone. Temozolomide therapy was well tolerated by the patients. The larger series of patients and long-term follow-up of late toxic effects are needed for further confirmation.

Prospective Multicenter Study for Evaluating Cognitive Disorders in Hematology-Oncology: A Pilot Study of 118 Patients

Introduction: Cognitive impairment occurs in a subset of cancer survivors and is generally subtle. Most evidence suggests that chemotherapy may be a cause, although other factors associated with the diagnosis and treatment of cancer may contribute. Recently, recommendations for future research in evaluating cognitive disorders have been suggested though different published studies. Nevertheless, there is a need to standardize this evaluation, particularly for neuropsychological tests. The various domains to be explored include memory disorders, decrease in oral fluency, care and concentration, slowing down of information processing. The main objective of this prospective study was to assess the feasibility for evaluating cognitive disorders with neuropsychological tests in different groups of homogeneous patients. The secondary objectives were to evaluate the cognitive disorders in these groups of patients and the impact of disease and therapeutic strategies with a follow-up period of 48 weeks.Patients and Methods: 124 previously untreated patients were included by 13 centers. 5 subgroups were defined: group 1, breast cancer T1N0 treated by local radiotherapy (n=24); group 2, breast cancer T1–T2, N+ treated by adjuvant chemotherapy and radiotherapy (n=52); group 3, diffuse large B-cell lymphoma treated by chemotherapy plus rituximab (n=8); group 4 colon cancer treated by adjuvant chemotherapy (n=11); group 5, multiple myeloma treated by 4–5 cycles of VAD followed by high dose therapy and autologous transplantation (n=23). Exclusion criteria included previous cognitive disorders or neurological diseases, HIV patients, other cancers, previous vascular disease or head trauma, sleep apnea, brain metastasis, metabolic disorders or neuropsychiatric drug intake. Hetero-evaluation was performed three times by neuropsychologists, at inclusion (pre-therapeutic, except for group 5 where inclusion corresponded to the pre-transplantation period), second evaluation, (24 weeks after 1st visit (V) for groups 1–4 and 12 weeks for group 5), and 3rd evaluation (48 weeks or 24 weeks respectively for groups 1–4 or 5). Intra- and inter-comparisons were made. Neuropsychological tests were performed in similar order and included: Brown Petterson test; Grober and Buschke (16 items) test; Double work; letter, number sequence; D2 test; code test; trail-making test; Stroop test; oral fluency. Statistical analysis included Mantel Haenszel tests.Results : Mean age was 57.14 years (range 31–85), with a sex ratio F:M=5.3. Body mass index and blood pressure were not significantly different between groups. Performance status was different among groups particularly for groups 3–5. Baseline evaluation included other co-morbidities and anxiety/depression status which was slightly abnormal in 7% of the patients. Test feasibility was good for the majority of them but was dependent on the group of patients, particularly for oral fluency test (not performed in 27.3% of patients in group 4). In addition, the percentage of patients who did not have other controls (V 2 and 3) varied from one group to another, but concerned less than 24% of the patients (particularly for groups 3,4 and 5). A significant increase of the number of patients presenting an alteration at V 2 and 3 but normal at V1 was observed, particularly in the trail making test (altered in 26.2% of the patients) and Brown Petterson test altered particularly after 12 months of radiotherapy (37% of patients). The Empan test was improved at visit 3 particularly for group 2.Conclusion: This pilot prospective multicenter study allows todefine and validate neuro-psychological tests for evaluating cognitive disorders andestimate the percentage of patients having impaired cognitive functions due to treatment.

Patch-Test-Induced “Flare-Up” Reactions to Neomycin at Prior Biopsy Sites

"Recall dermatitis" classically refers to the uncommon phenomenon of chemotherapy-induced reactivation of skin damage originally induced by radiotherapy months or years earlier. We compare this condition to ectopic flare-up reactions presenting as dermatitis at existing or previous sites by an inducing agent. Enhanced sensitization of an existent allergen by patch testing is rarely described. We describe a case of a 61-year-old man's developing localized allergic contact dermatitis at previous neomycin-treated sites following the diagnosis of neomycin sensitivity on patch testing, which we attribute to a "flare-up" phenomenon.

Postoperative Radiotherapy of Glioblastoma Multiforme

Different factors influence glioblastoma patients' prognosis. The aim of this retrospective, explorative analysis was to define the role of recent treatment strategies and to examine the value of different prognostic factors. A total of 110 patients was analyzed. Complete resection, partial resection, and biopsy was accomplished in 69, 22, and 19 patients, respectively. 56 patients received conventionally fractionated radiotherapy with a median total dose of 60 Gy, 2 Gy daily. 54 patients received hyperfractionated accelerated radiotherapy with a median total dose of 54 Gy, 2 × 1.8 Gy daily. 20 patients had concomitant temozolomide (50–75 mg/m2/d), and 20 patients concomitant topotecan (0.5 mg/m2 as continuous venous infusion over 21 days). 37 patients received temozolomide as salvage therapy. Median overall (OS) and disease-free survival (DFS) were 8.7 and 4.8 months. After complete resection, partial resection, and biopsy, OS was 9.5, 8.5, and 5.5 months, respectively. OS was 8.5, 13.8, and 8.2 months for radiotherapy alone, concomitant temozolomide, and concomitant topotecan, respectively. Hazard ratio was 0.29 (OS; p = 0.002) and 0.32 (DFS; p = 0.003) for concomitant temozolomide compared to radiotherapy alone. Topotecan led to an increased toxicity. With 9.7 months for conventionally fractionated radiotherapy and 8.1 months for hyperfractionated radiotherapy, OS differed significantly (p = 0.003, log-rank test). OS in patients with RPA (recursive partitioning analysis) score III, IV, V, and VI was 14.1, 10, 9.5, and 5.8 months (p = 0.003, log-rank test). In the univariate (p = 0.0001, log-rank test) and multivariate analysis (p = 0.002, Cox regression), salvage temozolomide led to a statistically significant survival benefit (10.6 vs. 7.7 months). Concomitant topotecan or the use of hyperfractionated radiotherapy did not show to be superior in outcome in this retrospective analysis. Topotecan led to an increased toxicity. An attempt at complete resection is justified. Temozolomide should be integrated in therapy initially. As salvage therapy, temozolomide is also effective.

An analysis of adjuvant temozolomide plus radiotherapy vs radiotherapy alone in a single academic institution

1575 Background: The NCIC CE.3/EORTC 22981/26981 was open during the time period of August 2000 to March 2002. When the study closed, there existed a gap in care that did not address the ongoing management of patients (pts) with glioblastoma multiforme (GBM) that had been surgically excised. As a result of this gap, it was decided that the adjuvant use of temozolomide (TMZ) was to become the standard of care at our centre due to its lack of perceived toxicities and early evidence for its activity. Methods: An analysis was performed of all pts with GBM that were seen at the centre from 1998 to the summer of 2005. In total, 240 pts were identified across multiple medical and radiation oncologists. 75 pts were treated with radiotherapy (RAD) alone post surgery, 86 pts were treated with RAD + TMZ post surgery, 18 pts only had surgery and the remaining pts were unresectable. Average age was 59.7 years for pts treated only with RAD, and 54.6 years for those treated with TMZ + RAD (p = 0.028). 59% of pts treated with RAD were male, while 62% treated with RAD + TMZ were male. Median follow-up was 11.3 months for RAD and 15.7 months for TMZ + RAD (p = 0.0001816). Preliminary survival analysis demonstrates a 56% reduction in the risk of death for pts treated with TMZ + RAD when compared to RAD (log rank p = 9.6 × 10−6). Median survival was 12.7 months for pts treated with RAD and 27 months for pts treated with TMZ + RAD (see table ). A further analysis including recursive partitioning analysis (RPA) and duration of therapy post RAD will be attempted to confirm the similarities between the two groups. Conclusion: Adjuvant TMZ + RAD has increased overall survival by 14.3 months in our institution. Further analysis is necessary to determine the impact on duration of therapy of TMZ. [Table: see text] [Table: see text]

Does pretreatment human papillomavirus (HPV) titers predict radiation response and survival outcomes in cancer cervix?—A pilot study

Objective. To evaluate if pretreatment HPV titers in cancer cervix could predict radiation response and survival outcomes. Methods. Twenty-one patients of cancer cervix were treated by radiotherapy (RT) alone. HPV titers were estimated using DNA Hybrid Capture II test. Loco-regional response at 1 month of RT – complete or partial response (CR and PR respectively) and survival outcomes – local disease-free (LDFS), disease-free (DFS) and overall (OS) survivals were evaluated against pre- and posttreatment HPV titers. Results. Pretreatment HPV titers ranged from 0.81 to 3966.10 RLU/cut off (mean ± SD: 1264.39 ± 1148.22, median: 1129.98). Of the demographic features evaluated, mean HPV titers were significantly different only for patients achieving CR or PR at completion of RT (mean ± SD for CR vs. PR: 1616.31 ± 1146.86 vs. 384.57 ± 538.80, P = 0.022). HPV titers at end of RT ranged from 0.12 to 487.42 RLU/cut off (mean ± SD: 37.31 ± 108.60, median: 2.33). Patients with higher pretreatment HPV titers (>1000 RLU/cutoff) had a higher CR ( P = 0.022) and better survival compared to those with ≤1000 RLU/cutoff (LDFS, P = 0.004; DFS, P = 0.005; OS, P = 0.012). At completion of RT, those having ≥99.5% fall in HPV had superior survival outcomes than those with <99.5% reduction (LDFS, P = 0.002; DFS, P = 0.002; OS, P = 0.004). Conclusions. Higher pretreatment HPV titers (>1000 RLU/cutoff) could be considered as a predictor of radiotherapy response and survival in cancer cervix. A reduction in these titers to 99.5% of their baseline values at end of radiotherapy is also associated with better survival outcomes.

Efficacy of intensified hyperfractionated and accelerated radiotherapy and concurrent chemotherapy with carboplatin and 5-fluorouracil: Updated results of a randomized multicentric trial in advanced head-and-neck cancer

To prove an expected benefit of concurrent radiochemotherapy (RCT), a two-arm randomized multicentric study was performed. In a subgroup analysis the influence of pretherapeutical hemoglobin level (p-Hb) on survival under locoregional control (SLC) was tested. The study included primarily untreated Stage III/IV (International Union Against Cancer [UICC]) oropharyngeal and hypopharyngeal carcinomas. Patients were randomized to receive either hyperfractionated (hf) and accelerated (acc) RCT with two cycles 5-fluorouracil (600 mg/m(2)/day) and carboplatin (70 mg/m(2)/day) on Days 1-5 and 29-33 or hf-acc radiotherapy (RT) alone. Total RT dose in both arms was 69.9 Gy in 38 days in concomitant boost technique. After a median follow-up time of 57 months, SLC is significantly better in RCT than in RT (p = 0.01), with median SLC of 17 months and 11 months, respectively. Also overall survival (OS) shows a benefit for RCT (p = 0.016), with a median survival of 23 months for RCT and 16 months for RT. However, the benefit in SLC and OS is not seen in hypopharyngeal carcinomas. In a multivariate analysis of oropharyngeal cancer patients, p-Hb levels lower than 12.7 g/dL resulted in lower SLC compared with higher p-Hb levels up to 13.8 g/dL. P-Hb levels >13.8 g/dL did not further improve SLC. Hyperfractionated-accelerated RCT is superior to hf-acc RT in oropharyngeal carcinomas. P-Hb levels >13.8 g/dL do not further improve SLC.

Concomitant Cisplatin Significantly Improves Locoregional Control in Advanced Head and Neck Cancers Treated With Hyperfractionated Radiotherapy

To determine whether the application of two courses of cisplatin simultaneously with hyperfractionated radiotherapy improves the outcome in locally advanced and/or node-positive nonmetastatic carcinomas of the head and neck, compared with hyperfractionated radiotherapy alone. From July 1994 to July 2000, 224 patients with squamous cell carcinomas of the head and neck (excluding nasopharynx and paranasal sinus) were randomly assigned to hyperfractionated radiotherapy (median dose, 74.4 Gy; 1.2 Gy twice daily) or the same radiotherapy combined with two cycles of concomitant cisplatin (20 mg/m2 on 5 days of weeks 1 and 5). The primary end point was time to any treatment failure; secondary end points were locoregional failure, metastatic relapse, overall survival, and late toxicity. There was no difference in radiotherapy between both treatment arms (74.4 Gy in 44 days). The full cisplatin dose was applied in 93% and 71% of patients during the first and second treatment cycles, respectively. Acute toxicity was similar in both arms. Median time to any treatment failure was not significantly different between treatment arms (19 months for combined treatment and 16 months for radiotherapy only, respectively) and the failure-free rate at 2.5 years was 45% and 33%, respectively. Locoregional control and distant disease-free survival were significantly improved with cisplatin (log-rank test, P = .039 and .011, respectively). The difference in overall survival did not reach significance (log-rank test, P = .147). Late toxicity was comparable in both treatment groups. The therapeutic index of hyperfractionated radiotherapy is improved by concomitant cisplatin.

Rate of resolution of exudative retinal detachment after plaque radiotherapy for uveal melanoma.

To determine the clinical relevance of exudative retinal detachment (ERD) and the rate of ERD resolution after plaque radiotherapy of posterior uveal melanomas. Retrospective, nonrandomized study of 135 consecutive patients with posterior uveal melanoma treated by iodine 125 plaque radiotherapy. Extent of ERD and tumor thickness were assessed before radiotherapy and at postoperative follow-up visits. Local tumor control was assessed at each follow-up visit. An ERD was present in 71 patients (53%) and was a risk factor for local treatment failure (P =.03). The ERD resolved after radiotherapy in 59 (83%) of the 71 patients. The ERD resolved within 1 year in 64 patients (90%) (mean time to resolution, 5.6 months). The rate of ERD resolution correlated with the rate of decrease in tumor thickness (P =.004). The ERD did not resolve and the tumor thickness continued to increase in 5 patients, who required further intervention. A recurrent retinal detachment developed in 5 patients, who were diagnosed as having rhegmatogenous retinal detachment (3 patients) and lipid exudation secondary to tumor vasculopathy (2 patients). Two patients with local tumor recurrence did not develop a recurrent ERD. Local tumor control was achieved in 130 patients (96%). An ERD may be a risk factor for local failure after plaque radiotherapy for uveal melanoma. If an ERD does not resolve within 9 to 12 months of radiotherapy and the tumor is not regressing, treatment failure should be suspected. A recurrent ERD does not necessarily represent local tumor recurrence.

Overexpression of Bcl-2 in squamous cell carcinoma of the larynx: a marker of radioresistance.

Squamous cell carcinoma of the larynx can be treated using radiotherapy or surgery, either alone or in combination. Radiotherapy is preferred for early-stage tumours, as it spares the larynx and therefore preserves speech and swallowing. Unfortunately, approximately 15% of tumours treated this way will prove to be radioresistant, as manifest by tumour recurrence within the original radiotherapy field over the ensuing 12 months. By causing extensive DNA damage, radiotherapy aims to induce apoptosis and tumour regression. Our hypothesis was that defects in the mechanisms that recognise DNA damage, induce cell cycle arrest or control apoptosis, either alone or in combination, may be responsible for radioresistance. We therefore undertook an immunohistochemic analysis of pretreatment biopsies of radioresistant (n = 8) and radiosensitive (n = 13) laryngeal tumours. To minimise the impact of confounding factors, strict inclusion criteria were observed; all tumours were of the glottic subsite and all recurrences developed within 12 months of radiotherapy at the site of the original tumour. The expression of key proteins involved in DNA damage recognition (p53), cell cycle arrest (ATM, p16 and p21/WAF1) and apoptosis (Bcl-2 and BAX) were studied. Ki-67 was also assessed as a marker of cell proliferation to exclude low mitotic rate as a cause of radioresistance. A statistically significant correlation was observed between overexpression of Bcl-2 and radioresistance (p = 0.003, Fisher's exact test). We hypothesise that overexpression of the anti-apoptotic protein Bcl-2 allows tumour cells with extensive radiation-induced DNA damage to continue proliferating; the absence of an appropriate apoptotic response manifests clinically as radioresistance.

High dose rate transurethral brachytherapy as a boost dose for localized adenocarcinoma of the prostate.

From September 1989 to February 1993, 11 patients with localized adenocarcinoma of the prostate were treated with pelvic external-beam radiation therapy followed by high dose rate (HDR) transurethral brachytherapy as a boost dose. External-beam radiation therapy was administered through opposed pelvic fields using a 60Co teletherapy unit to a tumor dose of 46-50 Gy in 23-25 fractions and followed by three fractions of transurethral brachytherapy, delivered using a 60Co HDR remote afterloading equipment. The treatment time was calculated using the prostatic capsule as the reference point. The dose calculated to be delivered to the capsule was 5 Gy/fraction, making a total of 15 Gy. The follow-up period ranged from 11 to 65 months, with a median follow-up time of 30 months. Local control was achieved in all patients. The prostate-specific antigen levels were normalized within 3 months of radiotherapy in 9 patients and within 3-6 months in the remaining 2. Transurethral brachytherapy appears to be a simple and feasible form of brachytherapy. Preliminary local control and radiotherapy-related morbidity rates are comparable to those of other forms of brachytherapy. Further follow-up is required for assessment of long-term local control and delayed radiotherapy-related morbidity.

Chemoradiotherapy versus radiotherapy alone for anal cancer: A retrospective comparison

Purpose : To evaluate the effect of adding one cycle of concomitant chemotherapy to curative radiotherapy on tumor control and toxicity in the treatment of anal cancer. Methods and Materials : One hundred twenty-five patients completed curative sphincter-conserving treatment, 57 with radiotherapy alone and 68 with concomitant chemo-radiotherapy. Compared with chemoradiotherapy patients, radiotherapy patients were older (median age 71 vs 63) and had less advanced tumors (T3-4 26% vs 51%). Radiotherapy patients were usually treated with a direct perineal cobalt field (mean dose 31 Gy at 5 cm/10 fractions/3 weeks), complemented in most cases by a sacral arc field, followed (mean dose 31 Gy at 5 cm/10 fractions/3 (mean dose 23 Gy, Paris system). The large majority of chemoradiotherapy patients received antero-posterior opposed 10 MV photon fields, including pelvic and inguinial nodes (mean dose 38 Gy/19 fractions/4 weeks), followed (mean split 42 days) by implant boost (mean dose 18 Gy). In addition, chemo-radiotherapy patients received starting on day 1 an IV bolus of Mitomycin-C, 0.4 mg/kg (maximum 20 mg) and a 5-day continuous infusion of 5-fluorouracil 600–800 mg/m 2/day. Median follow-up was 65 months for radiotherapy and 48 months for chemo-radiotherapy patients. Results : For all 125 patients at 5 years, overall survival was 65.5%, definitive local control 83% and local control with sphincter preservation 68%. Overall and stage for stage, there was no difference in overall, progression-free or cancer-specific survival, nor in local control, local-regional control, or sphincter preservation rates between patients treated with chemoradiotherapy vs. radiotherapy alone. There was no significant difference between the two groups regarding acute or late toxicity. Conclusion : This retrospective analysis does not confirm the efficacy of one course of simultaneous Mitomycin-C and5-fluorouracil, at least in association with full-dose radiotherapy incorporating Iridium-192 boost.

Shingles

SELECTED CASES Case 1 A 56-year-old woman with advanced lymphoma presented with numerous coalescing lesions confined to the distributions of the left maxillary and ophthalmic divisions of the fifth cranial nerve. Ulcerations were also apparent on the left hemipalate. She had completed radiotherapy months before, but she continued to receive aggressive, multidrug chemotherapy, with the last course within days of the onset of the rash. Lesions were culture positive for varicella-zoster virus (VZV). Treatment was begun with high-dose intravenous acyclovir and continued for 7 days until new vesicles stopped forming. Nonetheless, existing lesions evolved into a confluent eschar (Fig 1, left). She then experienced an episode of mental confusion and right-sided paresis presumed to be secondary to virus-associated granulomatous angiitis of the left middle cerebral artery. Then all the teeth in her left maxillary arch loosened and were lost. Left maxillary sinusitis developed, necessitating antibiotics and surgical creation of a

Definitive radiotherapy following prostatectomy: Results and complications

Thirty-four patients with carcinoma of the prostate treated by prostatectomy received postoperative external beam radiation. Sixteen patients were treated within 4 months of radical prostatectomy (group 1),12 patients were treated for prostate carcinoma following initial enucleative prostatectomy for benign hypertrophy (group 2) and 6 patients were treated for palpable local recurrence 4 to 10 years following radical prostatectomy (group 3). The indications for postoperative radiotherapy following radical prostatectomy included extracapsular extension, seminal vesicle invasion, peri-prostatic soft tissue involvement, positive margins or palpable local recurrence. Eighty-five percent of the patients received whole pelvic radiation. All patients then had a 2-week treatment rest followed by a reduced portal to the prostate bed to a dose of 6500 cGy. The local control rate after radiotherapy was 100% with a median follow-up of 4 years. The 5-year actuarial survival and disease-free survival rates for all patients were 82 and 72%, respectively. In group 1, the 5-year actuarial survival and disease-free survival rates were 100 and 91%, respectively. In group 2, these rates were 77 and 64%. Three of the six patients in group 3 died within 30 months of radiotherapy. Fourteen patients (41%) had mild to moderate treatment related symptoms including seven patients (21%) with lower extremity or genital edema, five patients (15%) with urinary stress incontinence, two patients (6%) with urethral stricture and three patients (9%) with proctitis. Six of eight patients who were potent prior to radiation retained potency thereafter. No severe complications occurred. We conclude that external beam radiation therapy administered after prostatectomy resulted in an acceptable therapeutic ratio with 100% local regional control, and an acceptable complication rate (41%).

Prostaglandin-like material extracted from squamous carcinomas of the head and neck

Tumour-associated prostaglandin-like material, assessed by bioassay, has been examined in 37 patients with primary and metastatic squamous carcinomas of the head and neck, previously treated by radiotherapy and chemotherapy followed by radical surgery. High amounts of prostaglandin-like material were extracted from tumours excised within 3 months of radiotherapy and chemotherapy. These amounts correlated with necrosis, inflammation and fibrosis, but not with tumour site, size or degree of differentiation. Most of the prostaglandins formed by these treated tumours thus seem to be associated with host stromal and inflammatory cells, rather than the neoplastic cells. The possible roles of prostaglandins in facilitating the spread of squamous carcinomas are discussed.

Symptomatic hypothalamic hypopituitarism following radiotherapy

Summary A patient is described who developed symptomatic hypopituitarism within 18 months of radiotherapy for nasopharyngeal carcinoma. Detailed investigation indicated a lesion at hypothalamic level. The effect of radiation on hypothalamic-pituitary function is discussed.