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C Orton

Publications and source records attributed to C Orton.

At least 19 recordsLinked to original sources
PubMed2005

Cross-sectional imaging in non-melanoma skin cancer of the head and neck.

AIM: To investigate in head and neck non-melanoma skin cancers (NMSCs) the accuracy of cross-sectional imaging for detection of local tumour extent, recurrent tumour and prediction of patient outcome. METHODS: This retrospective study included 33 NMSC patients (22 men, 11 women, median age 69 years) with 8 primary and 25 suspected recurrent tumours. The findings of magnetic resonance imaging (MRI) and computed tomography (CT) were compared with histopathology, and accuracy of MRI or CT in detecting local recurrence was determined. Extent of disease on imaging was compared with patient outcome assessed by clinical follow-up to a mean of 26.4 months. RESULTS: Lesions were identified in 29 patients, whose mean disease-free survival (DFS) was 25.5 months. In 4 of these cases, where imaging showed no invasion of deep structures, DFS was 56 months. In the other 25 cases DFS was 20.6 months, irrespective of treatment but varying with site of involvement. Of 19 patients treated with surgery, imaging of 16 showed deep invasion, which was confirmed at histology in 15 (93.7% accuracy), and 3 had superficial tumours on imaging all confirmed by histology (100% accuracy). Imaging accuracy for identifying recurrent tumour was 96% (24 of 25 patients). CONCLUSION: In NMSC, cross-sectional imaging accurately identifies tumour extent and local recurrence. The extent of disease and invasion of deeper structures predicts patient outcome.

Adult↗
PubMed2003

Microtubule assembly in cultured myoblasts and myotubes following nocodazole induced microtubule depolymerisation.

When myoblasts fuse into myotubes, the organisation of the cytoskeleton changes dramatically. For example, microtubules emanate in a radial array form the centrosome in myoblasts, but form linear arrays not linked to a centrosome in myotubes. It is not clear how these linear arrays are formed and nucleated. They could arise in a number of ways: by nucleation and release from centrosomal like structures, cytoplasmic assembly, breakage/severing or nucleation from non-centrosomal sites. To test which of the above mechanisms or combination of mechanisms are responsible we investigated the re-formation of microtubules after depolymerisation by nocodazole, using antibodies against pericentrin, gamma-tubulin, EB1, and tyrosinated alpha-tubulin. In myoblasts, we found that when microtubules were allowed to recover after complete depolymerisation with nocodazole, microtubule recovery began within 1 min and was complete after 5 min. Microtubules grew out from the centrosome, which was positively stained for gamma-tubulin or pericentrin. In untreated myotubes, microtubules were arranged in linear arrays, with EB1 at their ends. The pericentriolar protein, pericentrin was arranged in a band around the nucleus as well as discrete spots in the cytoplasm. In contrast, the microtubule nucleating protein gamma-tubulin was not found in a band around the nucleus, but was found in several punctuate spots throughout the cytoplasm. Further, when microtubules were allowed to recover, after complete depolymerisation with nocodazole, recovery was not as rapid as that seen in myoblasts, and we found that regrowth began with the formation of short microtubule fragments throughout the cytoplasm. Gamma-tubulin was associated with these fragments. These results suggest that in myotubes, nucleation of microtubules can be non-centrosomal.

Animals↗
PubMed2000

The American Brachytherapy Society recommendations for high-dose-rate brachytherapy for carcinoma of the cervix.

PURPOSE: This report presents guidelines for using high-dose-rate (HDR) brachytherapy in the management of patients with cervical cancer, taking into consideration the current availability of resources in most institutions. METHODS: Members of the American Brachytherapy Society (ABS) with expertise in HDR brachytherapy for cervical cancer performed a literature review, supplemented their clinical experience to formulate guidelines for HDR brachytherapy of cervical cancer. RESULTS: The ABS strongly recommends that definitive irradiation for cervical carcinoma must include brachytherapy as a component. Each institution should follow a consistent treatment policy when performing HDR brachytherapy, including complete documentation of treatment parameters and correlation with clinical outcome, such as pelvic control, survival, and complications. The goals are to treat Point A to at least a total low-dose-rate (LDR) equivalent of 80-85 Gy for early stage disease and 85-90 Gy for advanced stage. The pelvic sidewall dose recommendations are 50-55 Gy for early lesions and 55-65 Gy for advanced ones. The relative doses given by external beam radiation therapy (EBRT) vs. brachytherapy depend upon the initial volume of disease, the ability to displace the bladder and rectum, the degree of tumor regression during pelvic irradiation, and institutional preference. As with LDR brachytherapy, every attempt should be made to keep the bladder and rectal doses below 80 Gy and 75 Gy LDR equivalent doses, respectively. Interstitial brachytherapy should be considered for patients with disease that cannot be optimally encompassed by intracavitary brachytherapy. While recognizing that many efficacious HDR fractionation schedules exist, some suggested dose and fractionation schemes for combining the EBRT with HDR brachytherapy for each stage of disease are presented. These recommendations are intended only as guidelines, and the suggested fractionation schemes have not been thoroughly tested. The responsibility for the medical decisions ultimately rests with the treating radiation oncologist. CONCLUSION: Guidelines are established for HDR brachytherapy for cervical cancer. Practitioners and cooperative groups are encouraged to use these guidelines to formulate their treatment and dose-reporting policies. These guidelines will be modified, as image-based treatment becomes more widely available.

Antineoplastic Agents↗
PubMed2000

American brachytherapy society recommendations for clinical implementation of NIST-1999 standards for (103)palladium brachytherapy. The clinical research committee of the American Brachytherapy Society.

PURPOSE: Recent important developments in palladium-103 ((103)Pd) dosimetry mandate a reevaluation of (103)Pd brachytherapy prescribing practices. METHODS AND MATERIALS: The clinical research committee of the American Brachytherapy Society (ABS) convened a consensus session of brachytherapists and physicists to develop recommendations regarding future dose prescribing guidelines for National Institute of Standards and Technology (NIST-1999) calibrated (103)Pd sources. RESULTS: The ABS recommends that clinicians attempt to reproduce the implant doses delivered and reported in the literature through the past decade. CONCLUSIONS: The following should be immediately implemented for (103)Pd dosimetry: 1) All practicing physicians, physicists, dosimetrists, and suppliers implement NIST-1999 air-kerma strength standard for (103)Pd brachytherapy. 2) All treatment planning systems and dose calculation algorithms must be updated to reflect new dose rate constants. The AAPM-recommended validated value for Theraseed model 200 is 0.665 cGy h(-1) U(-1). The dose rate constant for the Mentor MED3633 seed is currently reported as 0.68 cGy h(-1) U(-1). This latter value and the values for seeds from other manufacturers are awaiting independent confirmation. 3) Physicians who previously prescribed 115 Gy for (103)Pd monotherapy prostate implants should now prescribe 125 Gy. When using (103)Pd as a boost following 45 Gy of external beam irradiation, 100 Gy should be prescribed instead of the previous 90 Gy. It is critical that all three changes be implemented concurrently, because they are interdependent.

Brachytherapy↗
PubMed1999

Neutron and photon clonogenic survival curves of two chemotherapy resistant human intermediate-grade non-Hodgkin lymphoma cell lines.

BACKGROUND: The potential role of neutron therapy in the management of intermediate-grade non-Hodgkin lymphoma (IGNHL) has not been examined because of the belief that the anticipated radiobiological effectiveness (RBE) would be uniformly very low. PURPOSE: To determine the fast neutron RBE for two chemotherapy-resistant IGNHL cell lines. METHODS AND MATERIALS: Conventional soft agar clonogenic survival curves following irradiation by 60Co and fast neutron were established for two IGNHL cell lines. These cell lines, WSU-DLCL2 and SK-DHL2B, were found in previous studies to be able to repair sublethal damage, and were also resistant to L-Pam and doxorubicin chemotherapy. RESULTS: When the surviving fraction after 2 Gy photon was chosen as the biological endpoint, the RBE for WSU-DLCL2 and SK-DHL2B measured 3.34 and 3.06. Similarly, when 10% survival was considered, the RBE for these two cell lines measured 2.54 and 2.59. The RBE, as measured by the ratios alpha neutron/alpha photon, for WSU-DLCL2, SK-DHL2B cell lines are 6.67 and 5.65, respectively. These results indicate that the RBE for these IGNHL cell lines is higher than the average RBE for cell lines of other histological types. CONCLUSION: Fast neutron irradiation may be of potential value in treating selected cases of IGNHL.

Cell Survival↗
PubMed1999

Radiobiological characterization of two human chemotherapy-resistant intermediate grade non-Hodgkin's lymphoma cell lines.

Intermediate grade non-Hodgkin's lymphoma (IGNHL) is generally considered a radiosensitive tumor that can be controlled with moderate radiation doses. Cell-survival curves of cell lines derived from IGNHL have been typically described to exhibit small or no shoulder, implying inability to accumulate or repair sublethal radiation damage. We characterize in this report the clonogenic radiation survival curves of two human IGNHL cell lines, WSU-DLCL2 and SK-DHL2B, established from patients who expired after having exhibited chemotherapy resistance of their tumors. The cells were irradiated with 60Co radiation at a dose rate of 85-100 cGy/min and cell survival data were analyzed according to the linear quadratic model. The alpha/beta values for WSU-DLCL2 and SK-DHL2B cells are 2 and 8.6, respectively. The corresponding SF2 are 0.42 and 0.35, respectively. Both cell lines are able to repair radiation-induced sublethal damage. These data indicate that these cells are only moderately radiosensitive.

Cell Survival↗
PubMed1999

Combined low-dose-rate brachytherapy and external beam radiation for cervical cancer: experience over ten years.

Cervical cancer was treated with a combination of external beam and intracavitary radiation during a 10-year period at Wayne State University. Data were collected for 216 patients treated radically with external beam radiation (EBRT) and low-dose-rate brachytherapy for cervical cancer between 1980 and 1991 at Wayne State University. Patient distribution by stage was IB, 20.8%; IIA, 7.4%; IIB, 26.9%; IIIA, 1.8%; IIIB, 40.7%; and IVA, 2.3 %. Survival curves were constructed using Kaplan-Meier methods and differences between groups were tested for significance using the log-rank test. Multivariate analysis was done using the Cox proportional hazards model. With a median follow-up of 114 months, actuarial disease-free survival for all patients was 60% at 5 years and 55% at 10 years. Actuarial 5-year survival for Stage IB was 79%; for Stage II, 59%; and for Stage III, 53%. There were 14/216 (6%) of patients with severe late complications. On univariate analysis, race was found to be statistically significant, with Caucasian patients having better survival than African American (P = 0.03). The survival for patients treated in shorter overall times was significantly higher (P<0.001), especially with treatment completion in under 58 days. The stepwise Cox multivariate analysis provided the following significant results: race (African American vs. Caucasian; P = 0.04, RR = 1.6), Stage (II vs. I, P = 0.004, RR = 2.6), Stage (III vs. I; P = 0.004, RR = 2.5), and overall treatment time (P = 0.006, RR = 1.62). Rates of local control, survival, and complications among women treated with combined external beam and intracavitary radiation for cervix cancer were similar to those of prior retrospective studies.

Actuarial Analysis↗
PubMed1999

The American brachytherapy society survey of brachytherapy practice for carcinoma of the cervix in the United States.

PURPOSE: The purpose of this study was to survey the brachytherapy practice for cervical cancer in the United States. METHODS: The Clinical Research Committee of the American Brachytherapy Society (ABS) performed a retrospective survey of individual physicians of the ABS and American Society of Therapeutic Radiologists and Oncologists regarding the details of the brachytherapy techniques they personally used in the treatment of cervical cancer patients for the year 1995. The replies (some of which may have been an estimate only) were tabulated. The scope of this survey did not allow us to verify the data by chart audits. RESULTS: A total of about 3500 questionnaires were mailed out; 521 responses were received. Of these responders, 206 (40%) did not perform any brachytherapy for carcinoma of the cervix in 1995. Of the other 315 responders reporting a total of 4892 patients treated in 1995, 88% used low dose rate (LDR) while 24% used high dose rate (HDR). There was a wide variation in the doses used. For LDR treatments, the median total external beam radiation therapy (EBRT) dose was 45 and 50 Gy and the LDR dose was 42 and 45 Gy for early and advanced cancers, respectively. For HDR treatments, the median EBRT dose was 48 and 50 Gy and the median HDR dose was 29 and 30 Gy for early and advanced cancers, respectively. The median dose per fraction was 6 Gy for a median of five fractions. Interstitial brachytherapy was used as a component of the treatment in 6% of the patients by 21% of responders. Very few responders treated with pulsed or medium dose rates. CONCLUSION: This retrospective survey showed the current brachytherapy practice pattern in the treatment of cervical cancer in the United States and can serve as a basis for future prospective national brachytherapy data registry. There was wide variation in the practice pattern, emphasizing the urgent need for consensus on these issues.

Brachytherapy↗
PubMed1996

Hyperfractionated conformal radiotherapy in locally advanced prostate cancer: results of a dose escalation study.

PURPOSE: This study was initiated to assess the incidence of chronic complications and histologic and biochemical control following hyperfractionated conformal radiotherapy in patients with locally advanced prostate cancer. METHODS AND MATERIALS: Between October 1991 and October 1994, 49 patients with locally advanced prostate cancer were entered on the first two dose levels of a prospective dose-escalation study using hyperfractionated three dimensional conformal radiotherapy. The first 25 patients received a minimum tumor dose of 78 Gy to the prostate and seminal vesicles in 6 weeks at 1.3 Gy, b.i.d. No increase in chronic toxicity compared with conventional radiotherapy was noted; therefore, an additional 24 patients were treated to a minimum tumor dose of 82.8 Gy to the prostate and seminal vesicles in 7 weeks at 1.15 Gy, b.i.d. Toxicity was scored according to the Radiation Therapy Oncology Group morbidity grading scale. Efficacy was assessed through scheduled postradiation prostate specific antigen values and ultrasound-guided biopsies. The median follow-up for the entire group was 20 months. RESULTS: The hyperfractionated external radiation was well tolerated with minimal acute morbidity. At 30 months, the actuarial probability of Grade 2 gastrointestinal toxicity was 17%. At 30 months, the actuarial probability of Grade 2 genitourinary toxicity was 16%. There was no statistically significant difference between the two dose levels. No Grade 3 or 4 gastrointestinal or genitourinary toxicity was noted. At 12 months, 84% of patients had a prostate specific antigen < or = 4; and 53% < or = 1 ng/ml. At 12 months, 71% of patients had post radiation biopsies that were either negative (55% or showed a marked therapeutic effect (16%). CONCLUSION: The use of hyperfractionated conformal radiotherapy facilitated dose escalation with no increase in chronic toxicity compared to standard doses. The initial tumor response based on prostate specific antigen measurements and postradiation biopsies is highly encouraging. Based on these results, an increase in dose to 87.4 Gy has been planned according to the schema of this ongoing dose escalation study.

Acid Phosphatase↗
PubMed1996

Multifractionated high-dose-rate brachytherapy with concomitant daily teletherapy for cervical cancer.

BACKGROUND: High-dose-rate (HDR) brachytherapy has been the preferred treatment for cervical cancer at Wayne State University since 1987. The outcome of the first 105 patients treated is analyzed. PURPOSE: To determine clinical efficacy of the HDR modality. METHODS: We reviewed 105 patients and evaluated the 88 patients treated for cervical carcinoma with HDR and external beam radiotherapy (EBRT) from August 1987 to December 1992. Patients received initial external radiation to the pelvis (total dose of 19.8 to 39.6 Gy in 11 to 22 fractions), followed by outpatient HDR brachytherapy (3 fractions/week, 386 cGy/fraction to Point A, total of 8 to 12 fractions) and concurrent daily EBRT (1.8 to 2.0 Gy) to lateral parametria. During the HDR period of treatment, step wedge transmission blocks were used to shield central pelvic tissue while treating peripheral pelvic tissues with EBRT. Patient distributions were as follows: 25, IB/IIA; 35, IIB/IIIA; and 28, IIIB/IVA. There were 56 African American and 32 Caucasian patients with mean age of 55 (range 19-89). The median follow-up was 33 months (range 20 to 76 months). Kaplan-Meier analysis was performed. RESULTS: Three-year survival rates were 88%, IB/IIA; 69%, IIB/IIIA; 56%, IIIB/IVA; and 72% overall. Local control was achieved in 71/88 (80%) of patients. Failure site was cervix or within the pelvis in 12 patients, distant metastasis only 17 patients, and combined local and distant in 5 patients. Of the failures, 82% (28/34) died within 2 years. There were 3 grade III/complications (3.4%). CONCLUSION: Results compare favorably with previous LDR experience.

Adult↗
PubMed1996

Comparison of hyperfractionated conformal photon with conformal mixed neutron/photon irradiation in locally advanced prostate cancer.

In an attempt to improve the probability of complication-free local control for patients with locally advanced prostate cancer, a series of dose-finding studies have been conducted at Wayne State University using conformal neutron and hyperfractionated photon irradiation. In total, 96 patients with locally advanced prostate cancer (T3/T4 N0/N1 M0, and/or Gleason score > or = 8) were treated in two prospective studies. Forty-seven patients received conformal neutron/photon (15 NGy + 18 PhGy) and 49 patients were treated in a dose-escalation study using conformal photons (25 patients/78 Gy and 24 patients/83 Gy minimum dose). The median follow-up for both studies was 20 months (range 6-36 months). There was no significant difference in the rate of chronic gastrointestinal (GI) or gastrourinary (GU) morbidity between the two groups. However, the neutron treated patients had a significantly higher rate of moderate (14%) and severe (12%) hip stiffness. The rates of prostate-specific antigen (PSA) decline and 12-month negative biopsy were comparable. In conclusion, the therapeutic gain of neo-adjuvant hormonal therapy in combination with photon hyperfractionation to 83 Gy appears identical to that seen with the mixed neutron-photon dose of 15 NGy + 18 PhGy. Further efforts at improving the therapeutic ratio of radiotherapy for patients with locally advanced prostate cancer should be undertaken.

Adenocarcinoma↗
PubMed1995

Concurrent outbreaks of pertussis and Mycoplasma pneumoniae infection: clinical and epidemiological characteristics of illnesses manifested by cough.

Concurrent outbreaks of illnesses that were manifested by cough and that were suspected to be due to Bordetella pertussis and Mycoplasma pneumoniae infection were investigated in a midwestern town in Illinois. Three studies were conducted: questionnaires on the clinical and epidemiological characteristics of illness were administered to patients; serological tests were performed to confirm the presence of each pathogen and to develop case definitions for each illness; and case definitions were applied to responses to a mail-in questionnaire for estimating the magnitude of both outbreaks. In 135 cases of suspected pertussis and 42 cases of suspected mycoplasmal infection, subjects had a cough for > or = 14 days (the pertussis outbreak case definition). Among 20 laboratory-confirmed cases, a cough for > or = 14 days had a specificity of 20% for pertussis, and a cough for > or = 28 days plus whoop and/or vomiting had a specificity of 90% for pertussis. Six hundred-seventeen pertussis cases per 100,000 population and 1,179 cases of M. pneumoniae infection per 100,000 population occurred. In this setting, the standard outbreak case definition for pertussis lacked adequate specificity to distinguish pertussis from mycoplasmal infection. The magnitude of each outbreak was greater than the number of reported cases suggested.

Adolescent↗
PubMed1993

Preliminary results of a hyperfractionated dose escalation study for locally advanced adenocarcinoma of the prostate.

The objective of this study was to build on our experience with 3-D conformal radiotherapy (CRT) by using a hyperfractionated dose escalation scheme to maximize the therapeutic ratio between improved local control and reduced morbidity in patients with locally advanced prostate cancer. Twenty patients with locally advanced (T3, T4) adenocarcinoma of the prostate were treated with a hyperfractionated radiotherapy schedule. All fields were designed with a conformal therapy based beam's eye view, 3-D planning system. The pelvic lymph nodes received 1.8 Gy/day to a total dose of 45 Gy in 5 weeks. Using partial transmission blocks, the prostate and periprostatic tissues received 1.3 Gy twice daily (minimum interval of 6 h) to a total dose of 78 Gy in 6 weeks. The dose was chosen by calculating the biologically effective dose (BED) which would produce the same effect in late reacting tissue but an increase for the tumor as our standard dose of 69 Gy delivered in 1.8-2.0 Gy fractions. The alpha/beta chosen for late damage was 3 Gy and 10 Gy was used for the tumor. All 20 patients completed the planned course of treatment. Although an increase in the tumor BED would be expected to result in increased acute effects, no significant worsening of acute side-effects was observed compared with standard treatment. All patients had only mild (Grade 1) rectal or bladder toxicity during treatment. One patient had an exacerbation of diverticulitis during treatment requiring hospitalization for antibiotics but completed treatment on schedule.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗
PubMed1991

Initial experience with a practical hyperfractionated accelerated radiotherapy regimen.

This paper presents early results of a trial of a three-fractions-per-day (TID) regimen that is more convenient to schedule than the Continuous Hyperfractionated Accelerated Radiotherapy (CHART) protocol currently being tested in Europe. The treatment schedule used in the CHART regimen has been modified from 36 fractions of 1.5 Gy TID in 12 days to 72 fractions of 1.1 Gy in 24 treatment days, with all fractions delivered during normal working hours. With no weekend treatments, the entire course of radiotherapy is completed in less than 5 weeks. The doses used were determined using the L-Q model, with correction for incomplete repair between fractions and for accelerated repopulation of cancer cells. Comparison with historical controls shows statistically significant improvements both in CR rates for the primary tumor and in acute toxicity, as measured by reduced treatment interruptions. L-Q model calculations predict that, compared to the highest dose achieved in previous studies without exceeding tolerance, we are able to obtain a 12% increase in bioeffect dose to the primary tumor due to accelerating the treatment. An analysis of the potential tumoricidal effectiveness of this new treatment regimen shows that it should be better than several other accelerated fractionation schedules being tested for all values of Tpot. For short Tpot times, the advantage may be as much as one log cell kill, corresponding to a 10-15% potential improvement in local control.

Aged↗