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PubMed2004

Simulation of (125)I decay in a synthetic oligodeoxynucleotide with normal and distorted geometry and the role of radiation and non-radiation actions.

Within the track structure code PARTRAC, DNA strand break induction by direct and indirect radiation action was calculated for the E. coli catabolite gene activator protein (CAP) DNA complex with (125)I located at the position of the H(5) atom of the cytosine near the center. The shape of the resulting DNA fragment size distributions was found to be in reasonable agreement with corresponding experimental results. However, the calculated yield was considerably lower than the measured one. To study possible reasons for this, recently published experimental data on DNA strand breaks in a 41-mer synthetic oligodeoxynucleotide (oligoDNA) with incorporated (125)I were analyzed aiming at an evaluation of the non-radiation-related component due to the neutralization of the initially highly charged (125m)Te daughter ion. This was done by assuming that the differences between simulated radiation-induced distribution and the measured total fragment size distributions were due to the neutralization process. The neutralization effect defined in this way was found to dominate the strand breakage frequency within a range of 5-7 base pairs around the (125)I decay site on both strands. After implementing this neutralization effect derived from the oligoDNA analysis into the PARTRAC simulation for the CAP-DNA complex, the agreement of the calculated DNA fragment distributions with the corresponding experimental data was considerably improved. The results indicate that DNA conformation may be explored by incorporation of (125)I into the DNA, measurement of fragment size distributions, and comparison with simulation calculation for various hypothetical DNA models.

Computer Simulation↗
PubMed1989

Radiation therapy of seminoma: 17-year experience at the Joint Center for Radiation Therapy.

One hundred and sixteen patients with stage I and II primary testicular seminoma were treated at the Joint Center for Radiation Therapy (JCRT) between 1968 and 1984. Complete follow-up is available for 114 patients (98%) with a median follow-up time of 6 years. Actuarial relapse-free survival (RFS) and survival for the entire group at 10 years were 94 and 86%, respectively, with 27 patients still at risk beyond 10 years. Actuarial RFS and survival at 10 years by stage were 97 and 92% for stage I, 93 and 81% for stage IIa, 100 and 100% for stage IIb, but only 75 and 51% for stage IIc. The difference in actuarial survival between stage IIc patients and stage I, IIa and IIb patients was significant (p less than 0.01). These results indicate that radiation therapy is excellent treatment for stage I and II seminomas as long as the largest mass of disease is not greater than 5 cm (stage IIc). Patients with stage IIc seminoma are now treated with cisplatin-containing combination chemotherapy followed by radiation therapy to areas of bulk disease. Although the majority of patients with stage II disease in this series received mediastinal irradiation, this is no longer recommended at the JCRT.

Actuarial Analysis↗
PubMedDate not supplied

Misonidazole and unconventional radiation in advanced squamous cell carcinoma of the esophagus: a phase II study of the Radiation Therapy Oncology Group.

This is a report on Radiation Therapy Oncology Group (RTOG) Protocol No. 78-32, a Phase I/II prospective study aimed at determining tolerance, tumor response, and survival of squamous cell carcinoma of the esophagus treated with unorthodox fractionation radiotherapy combined with misonidazole. Misonidazole was administered by mouth 4 to 6 hr prior to radiation, at a dose of 1.0 to 1.25 Gm/.m2; blood levels were measured at about 4 hr after intake of the drug and reported in micrograms/ml. Radiotherapy was administered at 4 to 6 hr post-misonidazole dose and given with 400 rad fractions, alternating 2 or 3 times/week, up to 4,800 rad. A total of 43 patients were entered; 26 are evaluable for survival at 1 year post accession. Thirty patients (88%) received the planned radiation course. Twenty-eight patients (78%) received the planned misonidazole dosage. Tumor response, evaluable in 18 patients, showed a complete regression (C.R.) in only 2 patients (11%); and partial response (P.R.) in 6 patients (33%). Eight patients (44%) showed no tumor response to planned therapy. Toxicity was acceptable and in 38 evaluable patients only 4 reported (11%) nausea and vomiting, 7 reported mild paresthesias (18%). The median survival was only five months. In 26 patients evaluable for 1 year survival determination, only 1 survived (3.8%) this period. In view of the poor tumor response and low survival observed, we do not recommend that this particular fractionation regimen with misonidazole be used in a Phase III randomized trial in squamous cell carcinoma of the esophagus.

Adolescent↗
PubMed1988

Miniature radiation dosimeter for in vivo radiation measurements.

We have made initial characterization measurements on a miniature radiation dosimeter which can be used for in vivo radiation measurements. It consists of a radiation sensing field effect transistor (RADFET) mounted in a 0.8 mm OD plastic catheter. The RADFET acts as a dosimeter by storing trapped charge proportional to absorbed dose. The stored charge signal can be differentiated to give dose rate. We report on the techniques for mounting, a circuit for dose readout, drift of the readings, linearity of response, temperature and angular dependence, and unpowered operation of the device.

Radiometry↗
PubMed1991

Intraoperative radiation therapy of pancreatic carcinoma: a report of RTOG-8505. Radiation Therapy Oncology Group.

The Radiation Therapy Oncology Group in 1985 began a study of IORT plus external beam radiation therapy for patients with locally unresected, non-metastatic pancreatic cancer. Patients were treated with a combination of 2000 cGy of IORT and postoperative external beam radiation therapy to 5040 cGy in combination with IV 5-FU (500 mg/m2/day on the first 3 days of the external beam treatment). As patients were registered on study prior to exploration, it was expected that a number of patients would be excluded from further analysis at the time of surgery. Eighty-six patients were entered on study through 6/1/88 and analyzed through 4/90. Fifty-one patients were fully analyzable. Median survival time of the 51 patients was 9 months with an 18-month actuarial survival rate of 9%. Local control could not be adequately evaluated in this multi-institutional study. Major postoperative complications were not excessive and occurred in 12% of patients. Two patients had major late morbidity leading to death, one from duodenal bleeding and the second from biliary obstruction. Although this study does demonstrate the feasibility of IORT in a multi-institutional setting, it does not demonstrate any advantage of IORT over conventional therapy for this disease.

Carcinoma, Intraductal, Noninfiltrating↗
PubMed1992

Non-Hodgkin's lymphoma of the brain: can high dose, large volume radiation therapy improve survival? Report on a prospective trial by the Radiation Therapy Oncology Group (RTOG): RTOG 8315.

Between 1983 and 1987 the Radiation Therapy Oncology Group conducted a prospective phase II study to evaluate survival in primary non-Hodgkin's lymphoma of the brain treated with whole brain irradiation to 40 Gy and a 20 Gy boost to tumor plus a 2 cm margin. Forty-one patients are reported. Full follow-up is available on 35/41 who have died. Six are alive at 8.8-67.2 months from start of radiation therapy with a median followup of 53.9 months. Overall median survival was 11.6 months from start of radiation therapy and 12.2 months from diagnosis, with 48% surviving 1 year and 28% surviving 2 years. Karnofsky Performance Status and age were significant prognostic factors. Patients with a Karnofsky Performance Status of 70-100 had a median survival of 21.1 months compared to 5.6 months for patients with a status of 40-60 (p less than .001). Fourteen patients less than 60 years of age had a median survival of 23.1 months, while 27 patients greater than or equal to 60 years of age had a median survival of 7.6 months (log-rank p = .001). Disease recurred in the brain in 25/41 (61%) of the patients, (21/41 in the brain only and 4/41 in the brain plus distant metastases). Despite high dose and large volume irradiation, primary Central Nervous System lymphoma still exhibits excessive mortality, especially in older patients. This paradox of the relative radioresistance of primary Central Nervous System lymphoma remains unresolved.

Adult↗
PubMed2005

Implications of radiation dosimetry of the mandible in patients with carcinomas of the oral cavity and nasopharynx treated with intensity modulated radiation therapy.

Intensity modulated radiation therapy (IMRT) is a newer method of delivering highly conformal, salivary gland sparing radiation treatment that is finding increasing applications in head and neck malignancies. However, the radiation dose distribution to the mandible is rarely considered with IMRT, and the potential risks of osteoradionecrosis or osseointegrated implant failure are not well characterized for this modality. In a series of 10 patients with oral cavity and nasopharyngeal cancers who previously underwent IMRT, examination of the three-dimensional mandibular dose distribution was undertaken. The findings indicate a modest potential risk of osteoradionecrosis and osseointegrated implant failure in cases where IMRT optimization constraints are not specifically aimed at sparing the mandibular bone. Significantly higher mandibular doses (P < 0.04) were received in cases of oral cavity as opposed to nasopharyngeal cancers with IMRT. Efforts to optimize IMRT to further reduce doses to the mandible should be considered, and development of software tools to integrate three-dimensional dose distributions into planning of post-radiotherapy osseointegration would be beneficial.

Carcinoma↗
PubMed2004

The role of post-radiation therapy FDG PET in prediction of necessity for post-radiation therapy neck dissection in locally advanced head-and-neck squamous cell carcinoma.

PURPOSE: The role of neck dissection after radiation therapy ([RT] with or without chemotherapy) for regionally advanced head and neck cancer is controversial. As much as 50% of residual lymphadenopathy after radiation has no viable tumor cells present on histopathologic analysis. [(18)F] fluorodeoxyglucose positron emission tomography (FDG PET) imaging can detect metabolically active cancer. This study examines the ability of post-RT FDG PET imaging to predict the tumor status of residual lymphadenopathy after nonsurgical management of regionally advanced neck disease. METHODS AND MATERIAL: From February 2000 to October 2002, 41 patients were treated definitively by radiation (with or without chemotherapy) and underwent FDG PET and computed tomography (CT) imaging after treatment to assess response. Patients with negative CT and FDG PET scans were observed and did not undergo neck dissection. Patients with radiographically persistent lymphadenopathy underwent either neck dissection or fine-needle aspiration of the lymph nodes using ultrasound guidance. The results of the FDG PET scans were correlated with the pathologic findings. RESULTS: Twelve patients with persistent lymphadenopathy underwent either neck dissection or fine-needle aspiration. Four of the 12 were found to have viable residual tumor in the cervical lymph nodes. The pathology did not correlate with the size of the lymph nodes in the pre-RT or post-RT CT studies. However, the pathology correlated strongly with the post-RT FDG PET studies. All patients with a negative post-RT FDG PET or those with a maximum standardized uptake value (SUV(max)) of less than 3.0 in the post-RT FDG PET were found to be free of residual viable tumor. Using an SUV(max) of less than 3.0 as the criterion for a negative FDG PET study, the negative predictive value was 100% and the positive predictive value was 80%. CONCLUSIONS: A negative post-RT FDG PET scan is very predictive of negative pathology in neck dissection or fine-needle aspiration even with large residual lymphadenopathy. Therefore, if the post-RT FDG PET scan is negative, neck dissection might not be required for regional control. A prospective study with longer follow-up and greater patient numbers is needed to determine whether a policy of deferring neck dissection based on a negative FDG PET is supported.

Adult↗
PubMed2005

Radiation dosimetry predicts IQ after conformal radiation therapy in pediatric patients with localized ependymoma.

PURPOSE: To assess the effects of radiation dose-volume distribution on the trajectory of IQ development after conformal radiation therapy (CRT) in pediatric patients with ependymoma. METHODS AND MATERIALS: The study included 88 patients (median age, 2.8 years +/- 4.5 years) with localized ependymoma who received CRT (54-59.4 Gy) that used a 1-cm margin on the postoperative tumor bed. Patients were evaluated with tests that included IQ measures at baseline (before CRT) and at 6, 12, 24, 36, 48, and 60 months. Differential dose-volume histograms (DVH) were derived for total-brain, supratentorial-brain, and right and left temporal-lobe volumes. The data were partitioned into three dose intervals and integrated to create variables that represent the fractional volume that received dose over the specified intervals (e.g., V(0-20 Gy), V(20-40 Gy), V(40-65 Gy)) and modeled with clinical variables to develop a regression equation to estimate IQ after CRT. RESULTS: A total of 327 IQ tests were performed in 66 patients with infratentorial tumors and 20 with supratentorial tumors. The median follow-up was 29.4 months. For all patients, IQ was best estimated by age (years) at CRT; percent volume of the supratentorial brain that received doses between 0 and 20 Gy, 20 and 40 Gy, and 40 and 65 Gy; and time (months) after CRT. Age contributed significantly to the intercept (p > 0.0001), and the dose-volume coefficients were statistically significant (V(0-20 Gy), p = 0.01; V(20-40 Gy), p < 0.001; V(40-65 Gy), p = 0.04). A similar model was developed exclusively for patients with infratentorial tumors but not supratentorial tumors. CONCLUSION: Radiation dosimetry can be used to predict IQ after CRT in patients with localized ependymoma. The specificity of models may be enhanced by grouping according to tumor location.

Adolescent↗
PubMed2005

A phase I/II trial to evaluate three-dimensional conformal radiation therapy confined to the region of the lumpectomy cavity for Stage I/II breast carcinoma: initial report of feasibility and reproducibility of Radiation Therapy Oncology Group (RTOG) Study 0319.

BACKGROUND: This prospective study (Radiation Therapy Oncology Group Study 0319) examines the use of three-dimensional conformal external beam radiation therapy to deliver accelerated partial breast irradiation. Reproducibility, as measured by technical feasibility, was the primary end point with the goal of demonstrating whether the technique is widely applicable in a multicenter setting before a Phase III trial is undertaken. METHODS AND MATERIALS: This study was designed such that if fewer than 5 cases out of the first 42 patients evaluable were scored as unacceptable, the treatment would be considered reproducible. Patients received 38.5 Gy in 3.85 Gy/fraction delivered twice daily. The clinical target volume included the lumpectomy cavity plus a 10-15-mm margin bounded by 5 mm within the skin surface and the lung-chest wall interface. The planning target volume (PTV) included the clinical target volume plus a 10-mm margin. Treatment plans were judged as follows: (1) No variations (total coverage), 95% isodose surface covers 100% of the PTV and all specified critical normal tissue dose-volume histogram (DVH) limits met. (2) Minor variation (marginal coverage), 95% isodose surface covers between > or = 95% and <100% of the PTV. No portion of PTV receives <93% of prescription (isocenter) dose. All specified critical normal tissue DVH limits fall within 5% of the guidelines. (3) Major variation (miss), 95% isodose surface covers <95% of the PTV. Portion of PTV receives <93% of prescription isocenter dose. Any critical normal tissue DVH limit exceeds 5% of the specified value. RESULTS: A total of 58 patients were enrolled on this study between 8/15/03 and 4/30/04, 5 of whom were ineligible or did not receive protocol treatment. Two additional patients were excluded, one because the on-study form was not submitted, and the other because no treatment planning material was submitted. This primary end point analysis is based on the first 42 (out of 51) evaluable patients, which were accrued from 17 different institutions (31 centers were credentialed for case enrollment, but because of rapid accrual, not all centers were able to submit cases before trial closure). These 42 patients had the following characteristics: median age was 61 years; 48% had a maximum tumor dimension of <1 cm; 86% had invasive ductal carcinoma; 64% were postmenopausal; the location of tumor was upper outer for 40% and upper central for 21%; 79% had no chemotherapy, and 64% had no hormonal therapy. There were 4 cases with major variations (all 4 related to normal tissue DVHs exceeding 5% of the specified limit). A total of 32 cases with minor variations in treatment plans were detected (16 related to normal tissue DVHs exceeding the specified limits [by < or = 5%], 6 related to suboptimal coverage of the PTV, and 10 related to both). There were 6 cases with no variations. Of the 51 total evaluable patients, 1 additional major variation was noted (PTV receiving <93% of the prescription dose). An additional 5 cases with minor variations in treatment plans were detected (3 related to normal tissue DVHs exceeding the specified limits [by < or = 5%], 1 related to suboptimal coverage of the PTV, and 1 related to both). There were 3 more cases with no variations. CONCLUSION: Accelerated partial breast irradiation using three-dimensional conformal external beam radiation therapy was shown in this preliminary analysis of the first 42 evaluable patients to be technically feasible and reproducible in a multi-institutional trial using exceptionally strict dosimetric criteria.

Adult↗
PubMed2006

Boron neutron capture therapy using mixed epithermal and thermal neutron beams in patients with malignant glioma-correlation between radiation dose and radiation injury and clinical outcome.

PURPOSE: To clarify the correlation between the radiation dose and clinical outcome of sodium borocaptate-based intraoperative boron neutron capture therapy in patients with malignant glioma. METHODS AND MATERIALS: The first protocol (P1998, n = 8) prescribed a maximal gross tumor volume (GTV) dose of 15 Gy. In 2001, a dose-escalated protocol was introduced (P2001, n = 11), which prescribed a maximal vascular volume dose of 15 Gy or, alternatively, a clinical target volume (CTV) dose of 18 Gy. RESULTS: The GTV and CTV doses in P2001 were 1.1-1.3 times greater than those in P1998. The maximal vascular volume dose of those with acute radiation injury was 15.8 Gy. The mean GTV and CTV dose in long-term survivors with glioblastoma was 26.4 and 16.5 Gy, respectively. A statistically significant correlation between the GTV dose and median survival time was found. In the 11 glioblastoma patients in P2001, the median survival time was 19.5 months and 1- and 2-year survival rate was 60.6% and 37.9%, respectively. CONCLUSION: Dose escalation contributed to the improvement in clinical outcome. To avoid radiation injury, the maximal vascular volume dose should be <12 Gy. For long-term survival in patients with glioblastoma after boron neutron capture therapy, the optimal mean dose of the GTV and CTV was 26 and 16 Gy, respectively.

Adolescent↗
PubMed2001

Oxidation of p-hydroxybenzoic acid by UV radiation and by TiO2/UV radiation: comparison and modelling of reaction kinetic.

The phenolic compound p-hydroxybenzoic acid is very common in a great variety of agroindustrial wastewaters (olive oil and table olive industries, distilleries). The objective of this work was to study the photocatalytic activity of TiO2 towards the decomposition of p-hydroxybenzoic acid. In order to demonstrate the greater oxidizing power of the photocatalytic system and to quantify the additional levels of degradation attained, we performed experiments on the oxidation of p-hydroxybenzoic acid by UV radiation alone and by the TiO2/UV radiation combination. A kinetic model is applied for the photooxidation by UV radiation and by the TiO(2)/UV system. Experimental results indicated that the kinetics for both oxidation processes can be fitted well by a pseudo-first-order kinetic model. The second oxidation process can be explained in terms of the Langmuir-Hinshelwood kinetic model. The values of the adsorption equilibrium constant, K(pHB), and the second order kinetic rate constant, k(c), were 0.37 ppm(-1) and 6.99 ppm min(-1), respectively. Finally, a comparison between the kinetic rate constants for two oxidation systems reveals that the constants for the TiO2/UV system are clearly greater (between 220-435%) than those obtained in the direct UV photooxidation.

Catalysis↗
PubMed2000

Randomized phase III study comparing Best Supportive Care to Biafine as a prophylactic agent for radiation-induced skin toxicity for women undergoing breast irradiation: Radiation Therapy Oncology Group (RTOG) 97-13.

PURPOSE: To determine if Biafine compared to Best Supportive Care (BSC) is effective in minimizing or preventing radiation-induced dermatitis in women undergoing breast irradiation. METHODS AND MATERIALS: Patients were randomized between Biafine (n = 83) vs. BSC (n = 89). The institutions identified preference for BSC at the time of randomization. A no-treatment arm was allowed (16% received no treatment). Patients were instructed to apply randomized product three times a day, but not within 4 h of their daily RT session. Application began following their first radiation treatment and continued 2 weeks postradiation. Skin dermatitis was scored weekly utilizing the RTOG and ONS (Oncology Nursing Society) skin toxicity scales, a weekly patient satisfaction and quality-of-life questionnaire. RESULTS: Using the RTOG toxicity scale there was no overall difference for maximum dermatitis during RT between Biafine and BSC (p = 0.77). There was no difference in maximum toxicity by arm or breast size. There was an interaction between breast size and toxicity, with large-breasted women exhibiting more toxicity. Large-breasted women receiving Biafine were more likely to have no toxicity 6 weeks post RT. CONCLUSION: There was no overall difference between BSC and Biafine in the prevention, time to, or duration of radiation-induced dermatitis.

Adult↗
PubMed1997

Locally advanced rectal carcinoma: pelvic control and morbidity following preoperative radiation therapy, resection, and intraoperative radiation therapy.

PURPOSE: To determine the impact of intraoperative radiation therapy (IORT) combined with preoperative external beam irradiation and surgical resection in patients with locally advanced, unresectable rectal carcinoma. METHODS AND MATERIALS: Between 1982 and 1993, 40 patients with locally advanced colorectal cancer unresectable at initial presentation were treated with preoperative external beam radiation therapy (median dose 50.4 Gy). Thirty patients received concurrent 5-fluorouracil. Twenty-seven patients had primary tumors and 13 had recurrent disease; 1 patient had a solitary hepatic metastasis at the time of surgery. Four to 6 weeks after radiation, surgical resection was undertaken, and if microscopic or gross residual disease was encountered, IORT was delivered to the tumor bed. Patients with an unevaluable or high-risk margin were also considered for IORT. IORT was delivered through a dedicated 300-kVp orthovoltage unit. The median dose of IORT was 12.5 Gy (range 8-20). The dose was typically prescribed to a depth of 1-2 cm. The median follow-up was 33 months (range 5-100). RESULTS: Thirty-three patients were able to undergo a curative resection (83%). Five patients had gross residual disease despite aggressive surgery. Seven patients did not receive IORT: six because of clear margins, and one with gross disease that could not be treated for technical reasons. The remainder of the patients (26) received IORT to the site of pelvic adherence. The crude local control rates for patients following complete resection with negative margins were 92% for patients treated with IORT and 33% for patients without IORT. IORT was ineffective for gross residual disease. Pelvic control was none of four in this setting. The crude local control rate of patients with primary cancer was 73% (16 of 22), as opposed to 27% (3 of 11) for these with recurrent cancer. The 5-year actuarial overall survival and local control rates for patients undergoing gross complete resection and IORT were 64% and 75%, respectively. Seventeen of the 26 patients (65%) who received IORT experienced pelvic complications, as opposed to two patients (28%) who did not receive IORT. The incidence of complications was similar in the patients with primary versus recurrent disease. All cases were successfully treated with the placement of a posterior thigh myocutaneous flap. Of note, no pelvic osteoradionecrosis was seen in this series. CONCLUSION: Patients with locally advanced carcinoma of the rectum were aggressively treated with combined modality therapy consisting of preoperative external beam radiotherapy, surgery, and IORT. The pelvic control rate was 82% for patients with minimal residual disease. IORT failed to control gross residual disease. The incidence of pelvic wound healing problems was 65% in this series; however, a reconstructive procedure which replaced irradiated tissue with a vascularized myocutaneous flap was successful in treating this complication. We believe that IORT has therapeutic merit in the treatment of locally advanced rectal cancer, particularly in the setting of minimal residual disease.

Adult↗
PubMed1998

Volumetric and dosimetric evaluation of radiation treatment plans: radiation conformity index.

PURPOSE: The use of conformal radiation therapy has grown substantially during the last years since three-dimensional (3D) treatment planning systems with beams-eye-view planning has become commercially available. We studied the degree of conformity reached in clinical routines for some common diagnoses treated at our department by calculating a radiation conformity index (RCI). METHODS AND MATERIALS: The radiation conformity index, determined as the ratio between the target volume (PTV) and the irradiated volume, has been evaluated for 57 patients treated with 3D treatment plans. RESULTS AND CONCLUSION: The RCI was found to vary from 0.3 to 0.6 (average 0.4), a surprisingly low figure. The higher RCI is typical for pelvic treatments (e.g., prostate) and stereotactic treatments. The lower RCI is found for extended tumors, such as mammary carcinomas where the adjacent nodes are included. The latter is also valid for most lung cancer patients studied. The RCI gives a consistent method for quantifying the degree of conformity based on isodose surfaces and volumes. Care during interpretation of RCI must always be taken, since small changes in the minimum dose can dramatically change the treated volume.

Brain Neoplasms↗
PubMed2001

Radiation therapy alone or combined surgery and radiation therapy in squamous-cell carcinoma of the penis?

To assess the prognostic factors and the outcome in patients with squamous-cell carcinoma of the penis, a retrospective review of 41 consecutive patients with non-metastatic invasive carcinoma of the penis, treated between 1962 and 1994, was performed. The median age was 59 years (range: 35-76 years). According to the International Union Against Cancer (UICC) 1997 classification, there were 12 (29%) T1, 24 (59%) T2, 4 (10%) T3 and 1 TX (2%) tumours. The N-classification was distributed as follows: 29 (71%) patients with N0, 8 (20%) with N1, 3 (7%) with N2 and 1 (2%) with N3. Forty-four per cent (n=18) of the patients underwent surgery: partial penectomy with (n=4) or without (n=12) lymph node dissection, or total penectomy with (n=1) or without (n=1) lymph node dissection. 23 patients were treated with radiation therapy alone, and all but 4 of the patients who were operated upon received postoperative radiation therapy (n=14). The median follow-up period was 70 months (range 20-331 months). In a median period of 12 months (range 5-139 months), 63% (n=26) of the patients relapsed (local in 18, locoregional in 2, regional in 3 and distant in 3). Local failure (stump in the operated patients, and the tumour bed in those treated with primary radiation therapy) was observed in 4 out of 16 (25%) patients treated with partial penectomy +/-postoperative radiotherapy versus 14 out of 23 (61%) treated with primary radiotherapy (P=0.06). 15 (83%) out of 18 local failures were successfully salvaged with surgery. In all patients, 5- and 10-year survival rates were 57% (95% confidence interval (CI), 41-73%) and 38% (95% CI, 21-55%), respectively. The 5-year local and locoregional rates were 57% (95% CI, 41-73%) and 48% (95% CI, 32-64%), respectively. In patients treated with primary radiotherapy, 5- and 10-year probabilities of surviving with penis preservation were 36% (95% CI, 22-50%) and 18% (95% CI, 2-34%), respectively. In multivariate analyses, survival was significantly influenced by the N-classification, and surgery was the only independent factor predicting the locoregional control. We conclude that, in patients with squamous-cell carcinoma of the penis, local control is better in patients treated with surgery. However, there seems to be no difference in terms of survival between patients treated by surgery and those treated by primary radiotherapy +/-salvage surgery, with 39% having organ preservation.

Adult↗
PubMed2005

Farnesylated RhoB inhibits radiation-induced mitotic cell death and controls radiation-induced centrosome overduplication.

Our previous results demonstrated that expressing the GTPase ras homolog gene family, member B (RhoB) in radiosensitive NIH3T3 cells increases their survival following 2 Gy irradiation (SF2). We have first demonstrated here that RhoB expression inhibits radiation-induced mitotic cell death. RhoB is present in both a farnesylated and a geranylgeranylated form in vivo. By expressing RhoB mutants encoding for farnesylated (RhoB-F cells), geranylgeranylated or the CAAX deleted form of RhoB, we have then shown that only RhoB-F expression was able to increase the SF2 value by reducing the sensitivity of these cells to radiation-induced mitotic cell death. Moreover, RhoB-F cells showed an increased G2 arrest and an inhibition of centrosome overduplication following irradiation mediated by the Rho-kinase, strongly suggesting that RhoB-F may control centrosome overduplication during the G2 arrest after irradiation. Overall, our results for the first time clearly implicate farnesylated RhoB as a crucial protein in mediating cellular resistance to radiation-induced nonapoptotic cell death.

Animals↗
PubMed1998

Immunohistochemical prediction of radiation response and local control in radiation therapy for cervical cancer.

Prognosis of 64 cervical cancer patients treated with radiation therapy was analyzed by tumor expressions of c-erbB-2 oncoprotein (CerbB-OPE) and p53 protein (p53-PE), Ki-67 growth fraction (Ki-GF), and the mitotic index of proliferating cell population (pMI). Positivity of CerbB-OPE and p53-PE was 42.4% and 84.6%, respectively. Mean Ki-GF and pMI were 33.0% and 2.7%, respectively. Mean Ki-GF for CerbB-OPE was 38.3%, significantly higher than the 26.2% for the negative patients (p < 0.01). The mean pMI for CerbB-OPE was 2.00%, significantly lower than the 3.70% of the negative patients (p < 0.05). The 5-year survival rate of CerbB-OPE-positive patients was 44.4%, significantly lower than the 74.8% of negative patients (p < 0.01). The survival rates of Ki-GF < 33% was 44.7%, significantly lower than the 87.5% of Ki-GF > or = 33% (p < 0.01). The survival rates of pMI > or = 3.5% was 0%, significantly lower than the 81.8% of pMI < 3.5% (p < 0.001). The survival rates of p53-PE-positive and negative patients were 52.8% and 85.0%, respectively (p > 0.1). The poor prognosis of the cervical cancer with CerbB-OPE, lower Ki-GF, and higher pMI were due to local recurrence following radiation therapy. Multiple regression analysis indicated that pMI was the strongest prognostic factor and was followed by CerbB-OPE, tumor volume, and Ki-GF. In conclusion, the c-erbB-2 oncoprotein expression, Ki-67 growth fraction, and the mitotic index of proliferating cell population were considered to be effective prognostic factors in radiation therapy for cervical cancer.

Biomarkers, Tumor↗