Search PubMed⌕ Search

Biomedical subjects

T S Lawrence

Publications and source records attributed to T S Lawrence.

At least 37 records · Page 2Linked to original sources
PubMed2000

The role of p53 in gemcitabine-mediated cytotoxicity and radiosensitization.

PURPOSE: We compared the cytotoxic and radiosensitizing effects of gemcitabine (2',2'-difluoro-2'-deoxycytidine, dFdCyd), a clinically valuable radiosensitizer, in colon cancer RKO cells which differed in their p53 status. The parental RKO cells, RKO-P, contain wild-type p53 protein. In RKO-E6 cells, the p53 function has been disrupted by transfection of the cells with the human papillomavirus type-16 E6 gene. RESULTS: We found that the RKO-P cells were significantly more sensitive to dFdCyd-mediated cytotoxicity and apoptosis than RKO-E6 cells (IC10 39.3 +/- 5.3 nM and 62.0 +/- 6.9 nM, respectively). The cytotoxic effect of dFdCyd in RKO-P cells was accompanied by induction of the proapoptotic protein Bax at the time when p53 was induced. In contrast, similar treatment of RKO-E6 cells with dFdCyd resulted in only limited expression of Bax, suggesting that the cytotoxic effect of dFdCyd was mediated, in part, by a p53-dependent apoptosis pathway. We also studied the effect of dFdCyd on radiation sensitivity. We found that at minimally cytotoxic concentrations dFdCyd failed to radiosensitize either RKO-P or RKO-E6 cells, whereas at cytotoxic concentrations equal sensitization was produced. Finally, we assessed the influence of dFdCyd on cell cycle distribution. We found that dFdCyd synchronized RKO-P cells, whereas synchrony was not produced in p53-disrupted RKO-E6 cells. CONCLUSION: These results suggest that p53 status may influence dFdCyd-mediated apoptosis, cytotoxicity, and cell cycle progression but do not support an important role for p53 in radiosensitization.

Antimetabolites, Antineoplastic↗
PubMed2000

Escalated focal liver radiation and concurrent hepatic artery fluorodeoxyuridine for unresectable intrahepatic malignancies.

PURPOSE: To evaluate the response, time to progression, survival, and impact of radiation (RT) dose on survival in patients with intrahepatic malignancies treated on a phase I trial of escalated focal liver RT. PATIENTS AND METHODS: From April 1996 to January 1998, 43 patients with unresectable intrahepatic hepatobiliary cancer (HB; 27 patients) and colorectal liver metastases (LM; 16 patients) were treated with high-dose conformal RT. The median tumor size was 10 x 10 x 8 cm. The median RT dose was 58.5 Gy (range, 28.5 to 90 Gy), 1.5 Gy twice daily, with concurrent continuous-infusion hepatic arterial fluorodeoxyuridine (0.2 mg/kg/d) during the first 4 weeks of RT. RESULTS: The response rate in 25 assessable patients was 68% (16 partial and one complete response). With a median potential follow-up period of 26.5 months, the median times to progression for all tumors, LM, and HB were 6, 8, and 3 months, respectively. The median survival times of all patients, patients with LM, and patients with HB were 16, 18, and 11 months, respectively. On multivariate analyses, escalated RT dose was independently associated with improved progression-free and overall survival. The median survival of patients treated with 70 Gy or more has not yet been reached (16.4+ months), compared with 11.6 months in patients treated with lower RT doses (P =.0003). CONCLUSION: The excellent response rate, prolonged intrahepatic control, and improved survival in patients treated with RT doses of 70 Gy or more motivate continuation of dose-escalation studies for patients with intrahepatic malignancies.

Adult↗
PubMed2000

Lack of effect of TP53 status on fluorodeoxyuridine-mediated radiosensitization.

Substantial evidence suggests that TP53 (also known as p53) status can influence the response of cells to chemotherapy and radiation. We wished to determine if TP53 function affected the response of cells to fluoropyrimidines and radiation, a combination used for tens of thousands of patients each year. To assess the role of TP53 in fluoropyrimidine-mediated radiosensitization, we carried out experiments using RKO parental cells (wild-type TP53) and RKO cells overexpressing mutant TP53 (which blocks TP53 function) or expressing E6 (which degrades TP53). We found that TP53 function had no effect on the ability of fluorodeoxyuridine to increase radiation sensitivity. These findings are consistent with the hypothesis that the late G(1)-phase checkpoint, which is mediated by TP53, is not crucial to radiosensitization. Rather, the ability of cells to progress in to S phase in the presence of the drug, which is independent of TP53, is more closely associated with increased radiation sensitivity.

Antimetabolites, Antineoplastic↗
PubMed1999

Noninvasive quantitation of cytosine deaminase transgene expression in human tumor xenografts with in vivo magnetic resonance spectroscopy.

Analysis of transgene expression in vivo currently requires destructive and invasive molecular assays of tissue specimens. Noninvasive methodology for assessing the location, magnitude, and duration of transgene expression in vivo will facilitate subject-by-subject correlation of therapeutic outcomes with transgene expression and will be useful in vector development. Cytosine deaminase (CD) is a microbial gene undergoing clinical trials in gene-directed enzyme prodrug gene therapy. We hypothesized that in vivo magnetic resonance spectroscopy could be used to measure CD transgene expression in genetically modified tumors by directly observing the CD-catalyzed conversion of the 5-fluorocytosine (5-FC) prodrug to the chemotherapeutic agent 5-fluorouracil (5-FU). The feasibility of this approach is demonstrated in subcutaneous human colorectal carcinoma xenografts in nude mice by using yeast CD (yCD). A three-compartment model was used to analyze the metabolic fluxes of 5-FC and its metabolites. The rate constants for yCD-catalyzed prodrug conversion (k(1)(app)), 5-FU efflux from the observable tumor volume (k(2)(app)), and formation of cytotoxic fluorinated nucleotides from 5-FU (k(3)(app)) were 0.49 +/- 0.27 min(-1), 0.766 +/- 0.006 min(-1), and 0.0023 +/- 0.0007 min(-1), respectively. The best fits of the 5-FU concentration data assumed first-order kinetics, suggesting that yCD was not saturated in vivo in the presence of measured intratumoral 5-FC concentrations well above the in vitro K(m). These results demonstrate the feasibility of using magnetic resonance spectroscopy to noninvasively monitor therapeutic transgene expression in tumors. This capability provides an approach for measuring gene expression that will be useful in clinical gene therapy trials.

Animals↗
PubMed1999

Superiority of yeast over bacterial cytosine deaminase for enzyme/prodrug gene therapy in colon cancer xenografts.

The enzyme/prodrug strategy using bacterial cytosine deaminase (bCD) and 5-fluorocytosine (5-FC) is currently under investigation for cancer gene therapy. A major limitation for the use of bCD is that it is inefficient in the conversion of 5-FC into 5-fluorouracil. In the present study, we show that the K(m) of yeast cytosine deaminase (yCD) for 5-FC was 22-fold lower when compared with that of bCD. HT29 human colon cancer cells transduced with yCD (HT29/yCD) were significantly more sensitive to 5-FC in vitro than HT29 cells transduced with bCD (HT29/bCD). In tumor-bearing nude mice, complete tumor regression was observed in 6 of 13 HT29/yCD tumors in response to 5-FC treatment (500 mg/kg i.p. daily, 5 days a week for 2 weeks), whereas 0 of 10 HT29/bCD tumors were cured. Our study demonstrates an improved efficacy of the CD/5-FC treatment strategy when yCD was used. This enzyme has, therefore, a high potential to increase the therapeutic outcome of the enzyme/prodrug strategy in cancer patients.

Animals↗
PubMed1999

Resistance of paroxysmal nocturnal hemoglobinuria cells to the glycosylphosphatidylinositol-binding toxin aerolysin.

Paroxysmal nocturnal hemoglobinuria (PNH) is a clonal stem cell disorder caused by a somatic mutation of the PIGA gene. The product of this gene is required for the biosynthesis of glycosylphosphatidylinositol (GPI) anchors; therefore, the phenotypic hallmark of PNH cells is an absence or marked deficiency of all GPI-anchored proteins. Aerolysin is a toxin secreted by the bacterial pathogen Aeromonas hydrophila and is capable of killing target cells by forming channels in their membranes after binding to GPI-anchored receptors. We found that PNH blood cells (erythrocytes, lymphocytes, and granulocytes), but not blood cells from normals or other hematologic disorders, are resistant to the cytotoxic effects of aerolysin. The percentage of lysis of PNH cells after aerolysin exposure paralleled the percentage of CD59(+) cells in the samples measured by flow cytometry. The kinetics of red blood cell lysis correlated with the type of PNH erythrocytes. PNH type III cells were completely resistant to aerolysin, whereas PNH type II cells displayed intermediate sensitivity. Importantly, the use of aerolysin allowed us to detect PNH populations that could not be detected by standard flow cytometry. Resistance of PNH cells to aerolysin allows for a simple, inexpensive assay for PNH that is sensitive and specific. Aerolysin should also be useful in studying PNH biology.

Bacterial Toxins↗
PubMed1999

Estimation of tumor control probability model parameters from 3-D dose distributions of non-small cell lung cancer patients.

Tumor control probability (TCP) model calculations may be used in a relative manner to evaluate and optimize three-dimensional (3-D) treatment plans. Using a mathematical model which makes a number of simplistic assumptions, TCPs can be estimated from a 3-D dose distribution of the tumor given the dose required for a 50% probability of tumor control (D50) and the normalized slope (gamma) of the sigmoid-shaped dose-response curve at D50. The purpose of this work was to derive D50 and gamma from our clinical experience using 3-D treatment planning to treat non-small cell lung cancer (NSCLC) patients. Our results suggest that for NSCLC patients, the dose to achieve significant probability of tumor control may be large (on the order of 84 Gy) for longer (> 30 months) local progression-free survival.

Carcinoma, Non-Small-Cell Lung↗
PubMed1999

HPV16-E7 expression causes fluorodeoxyuridine-mediated radiosensitization in SW620 human colon cancer cells.

We have reported that HT29 colon cancer cells, which are radiosensitized by fluorodeoxyuridine (FdUrd), exhibit a greater increase in cyclin E-dependent kinase activity and progress further into S phase in the presence of FdUrd than do SW620 colon cancer cells, which are only minimally sensitized by this drug (Cancer Res 56: 3203, 1996). Although these findings suggested that the ability to progress into S phase in the presence of FdUrd permits cells to be radiosensitized, we wished to test this hypothesis by attempting to drive SW620 human colon cells into S phase by transducing them with the HPV16-E7 gene. Two-parameter flow cytometry showed that E7-transduced cells progressed through S phase after radiation and FdUrd treatment more rapidly than SW620 parental cells. We found that E7-transduced SW620 cells were significantly radiosensitized by FdUrd (100 nmol/L, 14 hours) with an enhancement ratio for 2 clones of 1.47 +/- 0.03 and 1.51 +/- 0.14, compared with 1.24 +/- 0.04 in SW620 parental cells. These data strongly support the hypothesis that dysregulation of S-phase progression is an important factor in FdUrd-mediated radiosensitization.

Antimetabolites, Antineoplastic↗
PubMed1999

Expression and properties of an aerolysin--Clostridium septicum alpha toxin hybrid protein.

Aerolysin is a bilobal channel-forming toxin secreted by Aeromonas hydrophila. The alpha toxin produced by Clostridium septicum is homologous to the large lobe of aerolysin. However, it does not contain a region corresponding to the small lobe of the Aeromonas toxin, leading us to ask what the function of the small lobe is. We fused the small lobe of aerolysin to alpha toxin, producing a hybrid protein that should structurally resemble aerolysin. Unlike aerolysin, the hybrid was not secreted when expressed in Aeromonas salmonicida. The purified hybrid was activated by proteolytic processing in the same way as both parent proteins and, after activation, it formed oligomers that corresponded to the aerolysin heptamer. Like aerolysin, the hybrid was far more active than alpha toxin against human erythrocytes and mouse T lymphocytes. Both aerolysin and the hybrid bound to human glycophorin, and both were inhibited by preincubation with this erythrocyte glycoprotein, whereas alpha toxin was unaffected. We conclude that aerolysin contains two receptor binding sites, one for glycosyl-phosphatidylinositol-anchored proteins that is located in the large lobe and is also found in alpha toxin, and a second site, located in the small lobe, that binds a surface carbohydrate determinant.

Aeromonas↗
PubMed1999

Decreased 13-S-hydroxyoctadecadienoic acid levels and 15-lipoxygenase-1 expression in human colon cancers.

13-S-Hydroxyoctadecadienoic acid (13-S-HODE), the product of 15-lipoxygenase (15-LOX) metabolism of linoleic acid, enhances cellular mitogenic responses to certain growth factors. Other observations have questioned whether 13-S-HODE has tumorigenic effects. Our study evaluated the hypothesis that 15-LOX-1 is overexpressed in colon cancers resulting in an increase in intracellular 13-S-HODE. 15-LOX-1 and 13-S-HODE were quantified using western blots, ELISA and immunohistochemistry in 18 human colon cancers with paired normal colonic mucosa. Additionally, 15-LOX-1 expression was measured by western blots in three transformed colonic cell lines and in a human umbilical vein endothelial cell line. Next, we evaluated 13-S-HODE effects on cellular proliferation, cell cycle distribution and apoptosis in a transformed colonic cell line (RKO). Cell cycle distributions were measured by flow cytometry and apoptosis was assessed by phase contrast microscopy, electron microscopy, flow cytometry and DNA fragmentation assay. 15-LOX-1 immunohistochemistry staining scores were reduced in tumor tissues (P </= 0.0001) and 15-LOX-1 expression was absent in three transformed colonic cell lines. 13-S-HODE levels were also reduced in tumors tissues compared with normal controls by ELISA (median 3.3-fold, P = 0.02) and by immunohistochemistry (P </= 0.0001). In vitro 13-S-HODE inhibited RKO cell proliferation and induced cell cycle arrest and apoptosis. 13-S-HODE produced similar effects in HT-29 cells. Our observations indicate that: (i) human colon cancers are associated with a down-regulation in 15-LOX-1 expression and a reduction in 13-S-HODE intracellular levels; (ii) 13-S-HODE can suppress cell proliferation and induce apoptosis in transformed colonic epithelial cells.

Apoptosis↗
PubMed1999

Bromodeoxyuridine alternating with radiation for advanced uterine cervix cancer: a phase I and drug incorporation study.

PURPOSE: Preclinical studies show a significant increase in the ratio of the radiosensitizer bromodeoxyuridine (BUdR) in tumors versus the intestinal mucosa during the drug elimination period, compared with the ratio during drug infusion. We constructed a phase I study in patients with locally advanced cervix cancer, using alternating cycles of BUdR and radiation therapy (RT). PATIENTS AND METHODS: Eighteen patients with stage IIB to IVA cervix cancer participated. A treatment cycle consisted of a 4-day BUdR infusion followed by a week of pelvic RT, 15 Gy twice daily in 1.5-Gy fractions. After three cycles, additional BUdR was infused, followed by brachytherapy. The fraction of thymidine replaced by BUdR and the fraction of cells incorporating BUdR were determined in rectal mucosa and tumor biopsies at the end of the first BUdR infusion (day 5), at the middle of the first RT week (day 10), and at the time of brachytherapy. RESULTS: Dose-limiting toxicity was observed in one of 16 patients receiving 1,000 mg/m2/d x 4 days and in both patients receiving 1,333 mg/m2/d x 4 days each cycle. After a median follow-up of 39 months, 12 patients (66%) were free of pelvic disease and nine (50%) were alive and disease free. The ratio of tumor to rectum BUdR incorporation averaged 1.5 to 1.8 and did not differ significantly between day 5 and day 10. A trend toward reduced ratio was observed at brachytherapy. Drug-containing cells in rectal biopsies migrated from the crypts to the mucosal surface. CONCLUSION: In this schedule, 1,000 mg/m2/d is the maximum-tolerated dose of BUdR. BUdR incorporation levels in tumors were consistent with clinically significant radiosensitization. The migration of BUdR-containing rectal mucosa cells from the crypts to the surface at the time of RT suggests that this regimen may offer a relative sparing of the mucosa from radiosensitization.

Adenocarcinoma↗
PubMed1999

Radiosensitization by gemcitabine.

Gemcitabine is a potent radiosensitizer in both laboratory studies and in the clinic. Initial laboratory studies showed that gemcitabine radiosensitizes a wide variety of rodent and human tumor cells in culture. Maximum radiosensitization occurs in cells that demonstrate concurrent redistribution into S phase and d-adenosine triphosphate pool depletion. Although the mechanism of sensitization is not yet clear, recent evidence from our laboratory suggests that gemcitabine lowers the threshold for radiation-induced apoptosis. Our preclinical data were used to design gemcitabine dose-escalation trials in combination with standard radiation for patients with unresectable head and neck cancer and pancreatic cancer. In head and neck cancer, we have found that gemcitabine doses far below the maximum tolerated dose for the drug when used alone significantly potentiate the toxicity of treatment. Comparatively, normal tissue sensitization has not been as marked in the treatment of pancreatic tumors. These findings have led us to conduct experiments using an animal model to improve the therapeutic index of treatment. We conclude that gemcitabine is a promising radiation sensitizer that will need to be developed cautiously if excessive normal tissue toxicity is to be avoided.

Animals↗
PubMed1998

Improvement of CT-based treatment-planning models of abdominal targets using static exhale imaging.

PURPOSE: CT-based models of the patient that do not account for the motion of ventilation may not accurately predict the shape and position of critical abdominal structures. Respiratory gating technology for imaging and treatment is not yet widely available. The purpose of the current study is to explore an intermediate step to improve the veracity of the patient model and reduce the treated volume by acquiring the CT data with the patients holding their breath at normal exhale. METHODS AND MATERIALS: The ventilatory time courses of diaphragm movement for 15 patients (with no special breathing instructions) were measured using digitized movies from the fluoroscope during simulation. A subsequent clinical protocol was developed for treatment based on exhale CT models. CT scans (typically 3.5-mm slice thickness) were acquired at normal exhale using a spiral scanner. The scan volume was divided into two to three segments, to allow the patient to breathe in between. Margins were placed about intrahepatic target volumes based on the ventilatory excursion inferior to the target, and on only the reproducibility of exhale position superior to the target. RESULTS: The average patient's diaphragm remained within 25% of the range of ventilatory excursion from the average exhale position for 42% of the typical breathing cycle, and within 25% of the range from the average inhale position for 15% of the cycle. The reproducibility of exhale position over multiple breathing cycles was 0.9 mm (2sigma), as opposed to 2.6 mm for inhale. Combining the variation of exhale position and the uncertainty in diaphragm position from CT slices led to typical margins of 10 mm superior to the target, and 19 mm inferior to the target, compared to margins of 19 mm in both directions under our prior protocol of margins based on free-breathing CT studies. For a typical intrahepatic target, these smaller volumes resulted in a 3.6% reduction in Veff for the liver. Analysis of portal films shows proper target coverage for patients treated based on exhale modeled plans. CONCLUSIONS: Modeling abdominal treatments at exhale, while not realizing all the gains of gated treatments, provides an immediate reduction in the volume of normal tissue treated, and improved reliability of patient data for NTCP modeling, when compared to current "free breathing" CT models of patients.

Diaphragm↗
PubMed1998

Preferential cytotoxicity of cells transduced with cytosine deaminase compared to bystander cells after treatment with 5-flucytosine.

In vitro experiments from our laboratory and others have suggested that herpes simplex virus thymidine kinase (HSV-TK)/ganciclovir (GCV) gene therapy depends on gap junctional intercellular communication (GJIC) to produce a strong bystander effect. Furthermore, we have shown that cells transduced with HSV-TK can be protected from GCV-mediated toxicity by GJIC with bystander cells. We wished to determine whether GJIC affected either the bystander or protective effect of the cytosine deaminase (CD)/5-flucytosine (5-FC) gene therapy approach, in which CD converts 5-FC to 5-fluorouracil (5-FU). To test this, we designed a coculture system using communication-competent WB rat hepatocytes and a noncommunicating subclone (aB1), which were transduced with CD and with antibiotic resistance genes so that we could independently determine the survival of the CD-containing or bystander cells. We found that, compared to the HSV-TK/GCV strategy, bystander killing resulting from treatment with CD/5-FC does not depend on GJIC. However, our most striking finding was that both communication-competent and -incompetent CD-transduced cells were preferentially killed, by a factor of up to 500, compared to bystander cells. The lesser dependence of the CD/5-FC system on GJIC, combined with the finding that most cancer cells lack the capacity for GJIC, suggest that the CD/5-FC system may be superior to the HSV-TK/GCV approach for gene therapy. However, the premature death of the CD-transduced 5-FU "factory" suggests that other strategies may be necessary to produce a sufficient quantity of 5-FU for a duration long enough to produce permanent tumor regression.

Animals↗
PubMed1998

The effect of activation of wild-type p53 function on fluoropyrimidine-mediated radiosensitization.

PURPOSE: We have hypothesized that fluoropyrimidine-mediated (FdUrd) radiosensitization occurs in cells that inappropriately enter S phase in the presence of drug, resulting in defective repair of radiation-induced DNA damage (14). This model would predict that prevention of entry into S phase would abrogate sensitization produced by FdUrd. We wished to test this prediction by blocking S phase entry of HT29 human colon cancer cells. METHODS: We used HT29 cells that had been transduced with a murine temperature-sensitive p53 (ts29G) and, as a control, HT29 cells transduced with a neomycin plasmid (HT29neo). The murine temperature-sensitive p53 demonstrates wild-type p53 function when cells are incubated at the permissive temperature (32 degrees C) and mutant p53 function at the nonpermissive temperature (38 degrees C). We determined the effect of wt p53 function on FdUrd-mediated radiosensitization and cell cycle progression. RESULTS: Incubation of ts29G cells at the permissive temperature (32 degrees C) activated p21 and blocked entry of cells into S phase. Whereas FdUrd greatly increased the radiosensitivity of HT29neo cells and ts29G cells incubated at 38 degrees C, FdUrd had no effect on the radiation sensitivity of ts29G cells incubated at the permissive temperature (32 degrees C). CONCLUSIONS: These findings are consistent with our hypothesis that FdUrd-mediated radiosensitization requires progression into S phase. It is possible that the heterogeneity of clinical responses seen after combined therapy with fluoropyrimidines and radiation is explained, in part, by differences among tumor cells in the control of S phase progression.

Antimetabolites, Antineoplastic↗
PubMed1998

Preoperative idoxuridine and radiation for large soft tissue sarcomas: clinical results with five-year follow-up.

BACKGROUND: Local control remains an important issue in the management of large soft tissue sarcomas. Radiation is the main adjuvant to surgery for local therapy of sarcomas, but it requires relatively high doses, hitherto considered prohibitive in areas such as the retroperitoneum. We developed a preoperative treatment approach to large soft tissue sarcomas that would deliver a high total dose of radiation administered in conjunction with the halogenated pyrimidine radiosensitizer idoxuridine (IdUrd). METHODS: Thirty-seven patients with large sarcomas of the head and neck, mediastinum, retroperitoneum, or extremity received three or five cycles of sequential IdUrd infusion (1000-1600 mg/m2/d x 5 d) alternating weekly with twice daily radiation (125-150 cGy per dose) and were then evaluated for resection. The delivered preoperative radiation dose was up to 6250 to 7500 cGy. RESULTS: Five patients (14%) had a partial response to preoperative therapy, and 28 of 37 patients underwent successful resection. There were no intra- or postoperative deaths. Local control was achieved in 19 of 28 resected patients, but in only 1 of 6 patients who remained unresectable despite therapy. With a median follow-up of 5.8 years, 28% of patients are alive with no evidence of disease, 17% are alive with disease, and 53% have died of their disease. CONCLUSIONS: Using the dose and schedule we employed, resection of large soft tissue sarcomas was possible after high-dose radiation delivered in conjunction with IdUrd. Although local control was acceptable, the high rate of distant failure represents a limitation of any local approach to the treatment of large soft tissue sarcomas and suggests the need for integration of this approach with an effective systemic therapy.

Adolescent↗
PubMed1998

Spinal cord dose from standard head and neck irradiation: implications for three-dimensional treatment planning.

BACKGROUND AND PURPOSE: Treatment with traditional standard field arrangements for patients with head and neck cancer rarely causes myelopathy. Often, initial treatment fields are reduced to avoid the spinal cord after 45 Gy has been delivered and the cord dose that is delivered by 'off-cord' fields is not calculated. To determine a conservative limit to set for the cord dose for conformally-planned field arrangements, the total spinal cord dose delivered with standard opposed lateral fields was evaluated. MATERIALS AND METHODS: Two types of treatment plans were evaluated for 10 patients enrolled on a parotid-sparing protocol for bilateral head and neck treatment, i.e. (1) standard opposed lateral fields, including large initial fields treating nodal volumes to 45 Gy, off-cord fields for an additional 25 Gy and electron nodal boost fields for an additional 5 Gy and (2) complex 3-D treatment planned field geometries with conformal dose distributions (actual treatment fields). Treatment fields for the protocol conformal plans were arranged so that the maximum cord dose was not to exceed 50 Gy. Dose-volume histograms for both types of planned treatments were analyzed. The maximum and minimum dose to the 1 cm3 cord volume receiving the highest dose were reported. RESULTS: The maximum dose to the cord from the standard composite plans was on average 52 Gy, with a range of 48.9-55.9 Gy. This consisted of an additional 6.3 Gy (average) from the scatter and block transmission dose from the off-cord lateral fields above the prescribed 45 Gy. For the conformal plans, the maximum dose was on average 49.4 Gy (which is protocol criteria). DISCUSSION AND CONCLUSION: The maximum spinal cord dose of 50 Gy set as a dose constraint for 3-D treatment planning for conformal plans is a comparable dose to that given in standard opposed lateral head and neck treatments and has been determined to be a conservative spinal cord dose limit, which we have applied in our clinic.

Head and Neck Neoplasms↗