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Howard D Thames

Publications and source records attributed to Howard D Thames.

At least 37 records · Page 2Linked to original sources
PubMed2004

Clinically relevant pneumonitis after sequential paclitaxel-based chemotherapy and radiotherapy in breast cancer patients.

BACKGROUND: Taxane-based chemotherapy has been associated with an increased risk of radiation pneumonitis in patients with breast cancer. To obtain additional information about this association, we investigated the association between paclitaxel chemotherapy and radiation pneumonitis in patients participating in a phase III randomized study. METHODS: Five hundred and twenty-four breast cancer patients were prospectively and randomly assigned to receive either four cycles of paclitaxel followed by four cycles of 5-fluorouracil, doxorubicin, cyclophosphamide (FAC) or eight cycles of FAC. One hundred and eighty-nine of these patients (100 in the paclitaxel-FAC group and 89 in the FAC group) subsequently underwent radiation therapy in our institution and had medical records available to review for pulmonary symptoms. In addition, a radiologist who was unaware of the type of treatment scored chest x-ray changes after radiation treatment. Crude rates of radiation pneumonitis were compared with chi-square or Fisher's exact test, and actuarial rates were assessed with Kaplan-Meier and log-rank tests. All statistical tests were two-sided. RESULTS: No difference in the rate of clinically relevant radiation pneumonitis was observed between the two groups (5.0% in the paclitaxel-FAC group versus 4.5% in the FAC group; difference = 0.5%, 95% CI = -6.6% to 5.5%; P = 1.00). Oral steroids for pneumonitis were taken by two patients in the paclitaxel-FAC group but by none in the FAC group, and no patient was hospitalized for or died of radiation pneumonitis. The paclitaxel-FAC group (39.3%) had a higher rate of radiographic changes after irradiation than the FAC group (23.7%; difference = 15.6%, 95% CI = -0.11% to 28.8%; P = .034). CONCLUSION: Patients with breast cancer treated with sequential paclitaxel, FAC, and radiation therapy appeared to have a very low rate of clinically relevant radiation pneumonitis that was no different from that of patients treated with FAC alone.

Adult↗
PubMed2004

Cluster models of dose-volume effects.

PURPOSE: Describe cluster models, normal-tissue complication probability models in which both the number and the spatial location of radiation-sterilized functional subunits play a role in defining complication probability. METHODS AND MATERIALS: Computer simulation was used to determine the maximum size cluster of sterilized subunits associated with a given dose distribution. Complications were associated with large clusters. RESULTS: Cluster models showed a volume effect, as increasing effect for constant dose when the volume increased or constant effect when the dose was reduced with increasing volume. Cluster models gave similar results to existing models when tissues were irradiated uniformly. With inhomogeneous dose distributions, on the other hand, different spatial distributions of "hot spots" may lead to different predictions of complication probability by cluster models. The result was that a higher complication probability resulted when hot spots were contiguous (clustered) than when they were dispersed, even if both situations are characterized by the same dose-volume histogram. A potential advantage of cluster models is to provide an easy, internally consistent way to predict complications arising from the inhomogeneous dose distributions that sometimes arise with intensity-modulated radiotherapy. CONCLUSION: Cluster models offer a new way to quantify complication probability in treatment situations in which a wide variety of hot-spot distributions occur.

Animals↗
PubMed2004

Factors predictive of having four or more positive axillary lymph nodes in patients with positive sentinel lymph nodes: implications for selection of radiation fields.

PURPOSE: The optimal design of radiation fields for patients with positive sentinel lymph nodes (SLNs) who do not undergo axillary dissection is unknown. We have previously shown that modified breast tangent fields can include most axillary Level I-II lymph nodes. We have also reported that irradiation of the axillary apex/supraclavicular fossa is indicated for patients with four or more positive axillary lymph nodes. To determine the optimal arrangement for patients with positive SLNs, we studied what factors predicted for having four or more positive lymph nodes. METHODS AND MATERIALS: We reviewed the records of 339 consecutive patients with one to three positive SLNs who underwent complete axillary dissection at our institution between 1995 and 2002. We separately analyzed the outcome for those initially treated with surgery (n = 265) and those receiving neoadjuvant chemotherapy (n = 74). A logistic regression model was used to identify independent factors predictive for four or more positive lymph nodes. RESULTS: A total of 28 of 265 patients in the initial surgery group and 20 of 74 patients in the neoadjuvant group had four or more positive lymph nodes. In the initial surgery group, the independent factors associated with four or more positive lymph nodes were no drainage seen on lymphoscintigraphy (rate, 38%, odds ratio [OR] = 5.4, p = 0.03), more than one positive SLN (rate, 24-42%, OR = 2.9, p = 0.02), and lymphovascular space invasion (LVSI; rate, 25%, OR = 4.8, p = 0.01). Of the 106 patients without any of these factors, only 2 had four or more positive lymph nodes. For the patients treated with neoadjuvant chemotherapy, the independent factors were clinical Stage III (rate, 48%, OR = 3.1, p = 0.03), more than one positive SLN (rate, 37-67%, OR = 4.8, p = 0.03), and LVSI (rate, 62%, OR = 8.1, p = 0.02). Of the 28 patients without any of these factors, only 1 had four or more positive lymph nodes. CONCLUSION: It is reasonable to treat with modified tangents fields that include most axillary Level I-II nodes for patients with one positive SLN who do not undergo axillary dissection if drainage is seen on lymphoscintigraphy and no LVSI is present. This approach is also reasonable for patients treated with neoadjuvant chemotherapy who have Stage II disease, no LVSI, and only one positive SLN. The remaining patients have a greater risk of having four or more positive lymph nodes, and, therefore, the high axilla/supraclavicular fossa should also be included in the radiation fields.

Adult↗
PubMed2004

Breast conservation after neoadjuvant chemotherapy: the MD Anderson cancer center experience.

PURPOSE: To determine patterns of local-regional recurrence (LRR) and ipsilateral breast tumor recurrence (IBTR) among patients treated with breast conservation therapy after neoadjuvant chemotherapy. PATIENTS AND METHODS: Between 1987 and 2000, 340 cases of breast cancer were treated with neoadjuvant chemotherapy followed by conservative surgery and radiation therapy. Clinical stage at diagnosis (according to the 2003 American Joint Committee on Cancer system) was I in 4%, II in 58%, and III in 38% of patients. Only 4% had positive surgical margins. RESULTS: At a median follow-up period of 60 months (range, 10 to 180 months), 29 patients had developed LRR, 16 of which were IBTRs. Five-year actuarial rates of IBTR-free and LRR-free survival were 95% and 91%, respectively. Variables that positively correlated with IBTR and LRR were clinical N2 or N3 disease, pathologic residual tumor larger than 2 cm, a multifocal pattern of residual disease, and lymphovascular space invasion in the specimen. The presence of any one of these factors was associated with 5-year actuarial IBTR-free and LRR-free survival rates of 87% to 91% and 77% to 84%, respectively. Initial T category (T1-2 v T3-4) correlated with LRR but did not correlate with IBTR (5-year IBTR-free rates of 96% v 92%, respectively, P =.19). CONCLUSION: Breast conservation therapy after neoadjuvant chemotherapy results in acceptably low rates of LRR and IBTR in appropriately selected patients, even those with T3 or T4 disease. Advanced nodal involvement at diagnosis, residual tumor larger than 2 cm, multifocal residual disease, and lymphovascular space invasion predict higher rates of LRR and IBTR.

Adult↗
PubMed2004

Dose-volume response analyses of late rectal bleeding after radiotherapy for prostate cancer.

PURPOSE: To compare the fits of various normal tissue complication probability (NTCP) models to a common set of late rectal toxicity data, with the aim of identifying the best model for predicting late rectal injury after irradiation. METHODS AND MATERIALS: Late toxicity data from 128 prostate cancer patients treated on protocol with three-dimensional conformal radiotherapy at The University of Texas M.D. Anderson Cancer Center (UTMDACC) were analyzed. The dose-volume histogram for total rectal volume, including contents, was obtained for each patient, and the presence or absence of Grade 2 or worse rectal bleeding within 2 years of treatment was scored. Five different NTCP models were fitted to the data using maximum likelihood analysis: the Lyman model, the mean dose model, a parallel architecture model, and models based on either a cutoff dose or a cutoff volume. RESULTS: All five of the NTCP models considered provided very similar fits to the UTMDACC rectal bleeding data. In particular, none of the more highly parameterized models (the four-parameter parallel model, three-parameter Lyman model, or three-parameter cutoff dose and volume models) provided a better fit than the simplest of the models, the two-parameter NTCP model describing rectal bleeding as a probit function of mean dose to rectum. CONCLUSION: No dose-volume response model has yet been identified that provides a better description of the UTMDACC rectal toxicity data than the mean dose model. Because this model has relatively low predictive accuracy, the need to identify a better model remains.

Dose-Response Relationship, Radiation↗
PubMed2004

Dose-volume conundrum for response of prostate cancer to brachytherapy: summary dosimetric measures and their relationship to tumor control probability.

PURPOSE: Although it is known that brachytherapy dose distributions are highly heterogeneous, the effect of particular dose distribution patterns on tumor control probability (TCP) is unknown. It is unlikely that clinical results will throw light on the question in the near future, given the long follow-up and detailed dosimetry required for each patient. We used detailed dose distribution data from 50 patients combined with radiobiologic parameters consistent with what is known about TCP curves for prostate cancer to study the changes in TCP that accompany gross dosimetric measures and particular dosing irregularities (e.g., moderate underdosing of large volumes vs. extreme underdosing of small volumes). METHODS AND MATERIALS: For each of the 50 patients with organ-confined prostate cancer who had undergone 125I prostate implants alone at our clinic, postimplant CT scans were obtained approximately 1 month after implantation. Dose distribution information was obtained from postimplant dosimetry. The percentage of the prostate volume receiving a specified dose was recorded from the respective differential dose-volume histograms in 10-Gy bins. In addition, the percentage of prostate volume underdosed at varying fractions of the prescription dose were determined, as was the minimal prostate dose. The log-normal distributions of the radiobiologic parameters [ln(initial clonogen number), alpha, and alpha/beta] were adjusted so that the predicted population parameters (steepness and location) of the dose-response curves for external beam radiotherapy agreed with the published estimates. The variability in the dose-volume details was increased by scaling the dose distributions by factors ranging from 0.7 to 1.5, thereby simulating, for each of the patients, nine new patients with different total doses but identical relative distributions of the dose over the voxels. Radiobiologic variability between the selected dose distributions was then removed by averaging >50 randomly chosen sets of radiobiologic parameters from the log-normal distributions to estimate the TCP for each of the dose distributions, giving some insight into the TCP variations with conventional dosimetric indexes and different patterns of underdosing. RESULTS: Using the 450 dose distributions created by expanding the 50-patient data set, the volume of the prostate that was extremely underdosed (between 50% and 70% of the prescription dose) was related to the volume that was moderately underdosed (between 80% and 100% of the prescription dose). We found that the individual TCP is greatly dependent on the inhomogeneous dose distribution and the dosimetric indexes, such as the volume of prostate receiving 100% of the prescribed dose (V100) and the maximal dose received by 90% of the prostate volume (D90), which, by themselves, are not always accurate predictors of control probabilities. In a multivariate analysis of the dependence of TCP on these parameters (V100, D90, minimal dose, and moderately and severely underdosed volumes), only D90 and the minimal dose were statistically significant. Generally speaking, however, a lower minimal dose means a lower TCP. CONCLUSION: The work described here was an hypothesis-generating study. Our results showed that even if the V100 and D90 are nearly identical for 2 patients, there can be (and frequently are) significant differences in the dose distributions in the subvolumes of the prostate. Under simulated dose-response conditions (i.e., with variations in the dose distribution), the D90 and minimal dose significantly affected the TCP but the V100 and the volumes moderately or severely underdosed did not. In general, one must consider the totality of the dose distribution to evaluate the dosimetric quality of a low-dose-rate prostate implant. TCP is not a monotonic function of extreme or moderate underdosing. In some instances, extreme underdosing of relatively small volumes may result in a greater TCP than moderate underdosing of relatively large volumes and vice versa.

Brachytherapy↗
PubMed2004

Predicting radiosensitivity using DNA end-binding complex analysis.

Previous reports have suggested that measuring radiosensitivity of normal and tumor cells would have significant clinical relevance for the practice of radiation oncology. We hypothesized that radiosensitivity might be predicted by analyzing DNA end-binding complexes (DNA-EBCs), which form at DNA double-strand breaks, the most important cytotoxic lesion caused by radiation. To test this hypothesis, the DNA-EBC pattern of 21 primary human fibroblast cultures and 15 tumor cell lines were studied. DNA-EBC patterns were determined using a modified electrophoretic mobility shift assay and were correlated with radiosensitivity, as measured by SF2. DNA-EBC analysis identified a rapidly migrating ATM-containing band (identified as "band-A") of which the density correlated with SF2 (0.02 </= SF2 </= 0.41) in primary fibroblasts (r(2) = 0.77). The DNA-EBC pattern of peripheral blood lymphocytes was identical to that of fibroblasts. In addition, band-A density correlated with SF2 (0.35 </= SF2 </= 0.80) in 15 human tumor cell lines (r(2) = 0.91). Densitometry of other bands, or total DNA-EBC binding, correlated more poorly with SF2 (r(2) < 0.45). These data indicate that DNA-EBC analysis may be a practical, clinically relevant predictor of tumor and primary cell radiosensitivity.

Cell Line↗
PubMed2004

Effect of reduced EGFR function on the radiosensitivity and proliferative capacity of mouse jejunal crypt clonogens.

BACKGROUND AND PURPOSE: Previous data indicate that the EGFR pathway is involved in the response of tumor cell lines to irradiation. To determine if this receptor plays a role in the response of the intestinal mucosa, the effect of a spontaneous mutation in EGFR (B6C3-a-wa-2) on radiosensitivity and proliferative capacity was investigated using in vivo clonogenic assays and immunohistochemistry. PATIENTS AND METHODS: EGFR mutant mice were compared with wild-type mice using the in vivo jejunal microcolony assay using single and split doses to measure the radiosensitivity and repopulation of clonogenic jejunal mucosal cells. In addition, paraffin-embedded tissue sections were assessed for proliferation (PCNA), DNA repair (Ku70 and gamma H2AX), and apoptosis (TUNEL) by immunofluorescent staining (wild-type vs. heterozygous only) at various times after 5 Gy single dose. RESULTS: After the high doses used in the split-dose experiments, EGFR heterozygous and homozygous mutant mice were significantly more radiosensitive than their wild-type littermates. There was no clear difference in split-dose repair based on EGFR function. After 5 Gy single dose there were significantly more apoptotic cells within the crypts of heterozygous mice than of wild-type mice, beginning at 3h post irradiation. Decreased proliferation was observed only in the homozygous mutant mice. PCNA staining was lower in the heterozygous mice than in wild-type mice at 1 and 3 h post-5 Gy. CONCLUSION: The results indicate that after high doses the radiosensitivity of EGFR mutant mice is significantly higher than that of wild-type, and that this could be the result of an increase in apoptosis rather than reduced DNA repair. Proliferative capacity was modestly reduced, but only in the homozygous mutants.

Animals↗
PubMed2004

PSA after radiation for prostate cancer.

The introduction of prostate-specific antigen (PSA) as a reliable tumor marker for prostate cancer brought significant changes in the end points used for outcome reporting after therapy. With regard to a definition of failure after radiation, a consensus was reached in 1996 that took into account the particular issues of an intact prostate after therapy. Over the next several years, the consensus definition issued by the American Society for Therapeutic Radiology and Oncology (ASTRO) was used and studied. Concerns and criticisms were raised. The sensitivity and specificity of this definition vs other proposals has been investigated, and differences in outcome analyzed and compared. Although the ASTRO definition came from analysis of datasets on external-beam radiation and most of the work on this topic has been with this modality, failure definitions for brachytherapy must be explored as well. The concept of a universal definition of failure that might be applied to multiple modalities, including surgery, should also be investigated, at least for comparative study and research purposes.

Brachytherapy↗
PubMed2003

Long-term multi-institutional analysis of stage T1-T2 prostate cancer treated with radiotherapy in the PSA era.

PURPOSE: To report the long-term outcome for patients with Stage T1-T2 adenocarcinoma of the prostate definitively irradiated in the prostate-specific antigen (PSA) era. METHODS AND MATERIALS: Nine institutions combined data on 4839 patients with Stage T1b, T1c, and T2 adenocarcinoma of the prostate who had a pretreatment PSA level and had received >or=60 Gy as definitive external beam radiotherapy. No patient had hormonal therapy before treatment failure. The median follow-up was 6.3 years. The end point for outcome analysis was PSA disease-free survival at 5 and 8 years after therapy using the American Society for Therapeutic Radiology and Oncology (ASTRO) failure definition. RESULTS: The PSA disease-free survival rate for the entire group of patients was 59% at 5 years and 53% at 8 years after treatment. For patients who had received >or=70 Gy, these percentages were 61% and 55%. Of the 4839 patients, 1582 had failure by the PSA criteria, 416 had local failure, and 329 had distant failure. The greatest risk of failure was at 1.5-3.5 years after treatment. The failure rate was 3.5-4.5% annually after 5 years, except in patients with Gleason score 8-10 tumors for whom it was 6%. In multivariate analysis for biochemical failure, pretreatment PSA, Gleason score, radiation dose, tumor stage, and treatment year were all significant prognostic factors. The length of follow-up and the effect of backdating as required by the ASTRO failure definition also significantly affected the outcome results. Dose effects were most significant in the intermediate-risk group and to a lesser degree in the high-risk group. No dose effect was seen at 70 or 72 Gy in the low-risk group. CONCLUSION: As follow-up lengthens and outcome data accumulate in the PSA era, we continue to evaluate the efficacy and durability of radiotherapy as definitive therapy for early-stage prostate cancer. Similar studies with higher doses and more contemporary techniques will be necessary to explore more fully the potential of this therapeutic modality.

Adenocarcinoma↗
PubMed2003

The addition of continuous infusion 5-FU to preoperative radiation therapy increases tumor response, leading to increased sphincter preservation in locally advanced rectal cancer.

PURPOSE: To compare the outcome from preoperative chemoradiation (CXRT) and from radiation therapy (RT) in the treatment of rectal cancer in two large, single-institutional experiences. PATIENTS AND METHODS: Between 1978 and 1995, 403 patients with localized, nonmetastatic, clinically staged T3 or T4 rectal cancer patients were treated with preoperative RT alone at two institutions. Patients at institution 1 (n = 207) were treated with pelvic CXRT exclusively, and patients at institution 2 were treated (except for 8 given CXRT) with pelvic RT alone (n = 196). In addition, a third group (n = 61) was treated with CXRT at institution 2 between 1998 and 2000 after a policy change. Both institutions delivered 45 Gy in five fractions as a standard dose, but institution 2 used 20 Gy in five fractions in selected cases (n = 26). At both institutions, concurrent chemotherapy consisted of a continuous infusion of 5-fluorouracil (5-FU) at a dosage of 1500 mg/m(2)/week. The end points were response, sphincter preservation (SP), relapse-free survival (RFS), pelvic disease control (PC), and overall survival (OS). RESULTS: Median follow-up was 63 months for all living patients at institution 1 and in the primary group of institution 2. Multivariate analysis of the patients in these groups showed that the use of concurrent chemotherapy improved tumor response (T-stage downstaging, 62% vs. 42%, p = 0.001, and pathologic complete response, 23% vs. 5% p < 0.0001), but did not significantly improve LC, RFS, or OS. Follow-up for the secondary group at institution 2 was insufficient to allow the analysis of these endpoints. In the subset of patients receiving 45 Gy who had rectal tumors < or /=6 cm from the anal verge (institution 1: n = 132; institution 2 primary: n = 79; institution 2 secondary: n = 33), there was a significant improvement in SP with the use of concurrent chemotherapy (39% at institution 1 compared with 13% in the primary group at institution 2, p < 0.0001). A logistic regression analysis of clinical prognostic factors indicated that the use of concurrent chemotherapy independently influenced SP in these low tumors (p = 0.002). This finding was supported by a 36% SP rate in the secondary group at institution 2. Thus SP increased after the addition of chemotherapy at institution 2. CONCLUSIONS: The use of concurrent 5-FU with preoperative radiation therapy for T3 and T4 rectal cancer independently increases tumor response and may contribute to increased SP in patients with low rectal cancer.

Academic Medical Centers↗
PubMed2003

Radiation for prostate cancer: use of biochemical failure as an endpoint following radiotherapy.

The introduction of prostate-specific antigen (PSA) as a reliable tumor marker for prostate cancer brought significant changes in endpoints after therapy and in outcome reporting. Over the last 15 years we have collected follow-up information in this new era and struggled with failure definitions using this new tool. Parameters for failure after radiation were especially controversial due to the fact that, unlike surgery, a variable amount of normal prostate function and PSA production remained. In 1996, the ASTRO Consensus Conference established a PSA failure definition based on the available information at the time. It was commonly used for outcome reporting subsequently although criticisms have been voiced and alternate definitions proposed. A recently assembled multi-institutional database was used both for long-term outcome reporting with external beam radiation and to test various other failure definitions. A summary of these results and the associated issues are presented here.

Humans↗
PubMed2003

Indium-111-capromab pendetide radioimmunoscintigraphy and prognosis for durable biochemical response to salvage radiation therapy in men after failed prostatectomy.

PURPOSE: We evaluated the prognostic significance of indium-111 (111In)-capromab pendetide imaging for patients with prostate cancer who underwent salvage radiotherapy (RT) for recurrent disease after prostatectomy. PATIENTS AND METHODS: Records were reviewed for all men who underwent 111In-capromab pendetide imaging at a single institution from February 1997 through December 1999. We identified 30 eligible men who were radiographically negative for metastatic disease, who had increasing serum prostate-specific antigen (PSA) after primary radical prostatectomy, and who received salvage RT. Clinical interpretations of indium monoclonal antibody (In-mab) scan results were compared with postsalvage RT PSA response. RESULTS: Using an American Society of Therapeutic Radiation and Oncology definition of PSA failure, in men with a positive scan in at least one location (n = 14), the cumulative 2-year PSA control after salvage RT was 0.38 +/- 0.13 (+/- SE) compared with 0.31 +/- 0.13 for men with a normal antibody scan in and outside the prostate fossa (n = 15; proportional hazard ratio [PHR] = 1.32; 95% confidence interval [CI], 0.52 to 3.36). For men with a positive antibody scan limited to the prostate fossa (n = 9), PSA control at 2 years was 0.13 +/- 0.12 (PHR 1.77; 95% CI, 0.65 to 4.85). The 2-year probability of PSA control after salvage RT for men with positive scan results outside the prostate bed irrespective of In-mab findings in the prostate fossa (n = 5) was 0.60 +/- 0.22 (PHR 0.81; 95% CI, 0.17 to 3.78). CONCLUSION: In contrast to previous reports, for patients with postprostatectomy biochemical relapse who received salvage RT, presalvage RT In-mab scan findings outside the prostate fossa were not predictive of biochemical control after RT.

Aged↗
PubMed2003

Response to preoperative chemoradiation increases the use of sphincter-preserving surgery in patients with locally advanced low rectal carcinoma.

BACKGROUND: Although controversial, some believe that preoperative chemoradiation increases the use of sphincter-preserving surgery in low rectal carcinoma patients. This article investigates the relationship between objective tumor response and sphincter preservation in low rectal carcinoma patients. METHODS: The authors reviewed the records of 238 patients with T3 or T4 low rectal carcinoma (< or = 6 cm from the anal verge) who underwent preoperative pelvic chemoradiation (45 Gy/25 fractions/5 weeks, n = 182 or 52.5 Gy/30 fractions/5 weeks, n = 56 with continuous infusion 5-fluorouracil at 300 mg/m(2), Monday to Friday) followed by mesorectal (n = 223) or local excision (n = 15). A logistic regression analysis was used to analyze the influence of objective tumor response (defined as complete clinical response) and other prognostic factors on sphincter preservation. Because degrees of partial response could not be objectively defined retrospectively, the influence of partial response on sphincter preservation could not be evaluated. RESULTS: Overall, 49% of patients (117 of 238) had sphincter-preserving surgery. The clinical complete response rate was 47%. Independent predictors of sphincter preservation included the year of surgery, tumor distance from the anal verge, circumferential tumor involvement, and response to chemoradiation. The sphincter preservation rate increased over the period of the study (from 28% [December 1989 to December 1992] to 44% [January 1993 to December 1996] to 67% [January 1997 to December 2000]). The difference in the rates of sphincter preservation according to response was most striking among patients with tumors 3 cm or less from the anal verge (44% vs. 22%, P = 0.01). The pelvic disease recurrence rate among patients undergoing sphincter-preserving surgery has been less than 10% since January 1993 and was not statistically different between the groups treated from January 1993 to December 1996 and from January 1997 to December 2000. CONCLUSIONS: There has been an increase in the use of sphincter-preserving surgery without an increase in pelvic disease recurrence over the past decade. Although not necessary for sphincter preservation, clinical response to preoperative chemoradiation independently contributed to sphincter-preserving surgery, particularly in patients with low rectal tumors.

Adult↗
PubMed2002

Pathologic tumor size and lymph node status predict for different rates of locoregional recurrence after mastectomy for breast cancer patients treated with neoadjuvant versus adjuvant chemotherapy.

PURPOSE: To compare the pathologic factors associated with postmastectomy locoregional recurrence (LRR) in breast cancer patients not receiving radiation who were treated with neoadjuvant chemotherapy (NEO) vs. adjuvant chemotherapy (ADJ). METHODS AND MATERIALS: We retrospectively analyzed the rates of LRR of subsets of women treated in prospective trials who underwent mastectomy and received chemotherapy but not radiation. These trials were designed to answer chemotherapy questions. There were 150 patients in the NEO group and 1031 patients in the ADJ group. In the NEO group, 55% had clinical Stage IIIA or higher vs. 9% in the ADJ group (p <0.001, chi-square test). RESULTS: Despite the more advanced clinical stage in the NEO group, the pathologic size of the primary tumor and the number of positive lymph nodes (+LNs) were significantly less in the NEO group than in the ADJ group (p <0.001 for both comparisons). However, the 5-year actuarial LRR rate was 27% for the NEO group vs. 15% for the ADJ group (p = 0.001, log-rank). The 5-year risk for LRR was higher in the NEO patients for all pathologic tumor sizes: 0-2 cm (18% vs. 8%, p = 0.011), 2.1-5 cm (36% vs. 15%, p <0.001), and >5 cm (46% vs. 28%, p = 0.028). The risk of LRR by the number of +LNs was similar in the NEO and ADJ groups, except for the subset of patients with > or =4 +LNs (53% vs. 23%, p <0.001). The rates of LRR in the patients with primary tumors measuring < or =2.0 cm and 1-3 +LNs were similar in both groups. However, for the patients with a pathologic tumor size of 2.1-5.0 cm and 1-3 +LNs, the LRR was higher in the NEO group than in the ADJ group (30% vs. 15%, p = 0.016). Most failures in this NEO subgroup had clinical Stage III disease. In a subset of NEO and ADJ patients matched for clinical stage, no significant differences were found in the rates of LRR according to primary tumor size and number of +LNs when these variables were analyzed independently. Again, however, differences were found in the subgroup of patients with tumors pathologically measuring 2.1-5.0 cm with 1-3 +LNs (32% NEO vs. 8% ADJ, p = 0.030). CONCLUSION: The rates of postmastectomy LRR for any pathologic tumor size are higher for patients treated with initial chemotherapy than for patients treated with initial surgery. Radiotherapy should be offered to all patients with > or =4 +LNs, tumor size >5 cm, or clinical Stage IIIA or greater disease, regardless of whether they receive neoadjuvant or postoperative chemotherapy. The information assessing LRR rates in patients with clinical Stage II disease who receive neoadjuvant chemotherapy, particularly if 1-3 lymph nodes remain pathologically involved, is insufficient to determine whether these patients should receive radiotherapy.

Adult↗
PubMed2002

Direct evidence that prostate tumors show high sensitivity to fractionation (low alpha/beta ratio), similar to late-responding normal tissue.

PURPOSE: A direct approach to the question of whether prostate tumors have an atypically high sensitivity to fractionation (low alpha/beta ratio), more typical of the surrounding late-responding normal tissue. METHODS AND MATERIALS: Earlier estimates of alpha/beta for prostate cancer have relied on comparing results from external beam radiotherapy (EBRT) and brachytherapy, an approach with significant pitfalls due to the many differences between the treatments. To circumvent this, we analyze recent data from a single EBRT + high-dose-rate (HDR) brachytherapy protocol, in which the brachytherapy was given in either 2 or 3 implants, and at various doses. For the analysis, standard models of tumor cure based on Poisson statistics were used in conjunction with the linear-quadratic formalism. Biochemical control at 3 years was the clinical endpoint. Patients were matched between the 3 HDR vs. 2 HDR implants by clinical stage, pretreatment prostate-specific antigen (PSA), Gleason score, length of follow-up, and age. RESULTS: The estimated value of alpha/beta from the current analysis of 1.2 Gy (95% CI: 0.03, 4.1 Gy) is consistent with previous estimates for prostate tumor control. This alpha/beta value is considerably less than typical values for tumors (> or =8 Gy), and more comparable to values in surrounding late-responding normal tissues. CONCLUSIONS: This analysis provides strong supporting evidence that alpha/beta values for prostate tumor control are atypically low, as indicated by previous analyses and radiobiological considerations. If true, hypofractionation or HDR regimens for prostate radiotherapy (with appropriate doses) should produce tumor control and late sequelae that are at least as good or even better than currently achieved, with the added possibility that early sequelae may be reduced.

Aged↗