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Biomedical subjects

J M Kurtz

Publications and source records attributed to J M Kurtz.

At least 19 recordsLinked to original sources
PubMed2006

Local therapy, systemic benefit: challenging the paradigm of biological predeterminism.

This paper briefly reviews the historical evolution of paradigms that have been purported to characterise the clinical behaviour of breast cancer, with the intention of guiding treatment approaches. Results from randomised clinical trials and the explosion of knowledge in the area of cancer biology have discredited the monolithic paradigms that had dominated thinking about breast cancer in the past. Contemporary notions of breast cancer biology recognise that, although some cancers disseminate well before becoming clinically detectable, acquisition of a metastatic phenotype can occur at any point (or not at all) in the local evolution of the tumour. As a consequence, both systemic and timely local--regional therapies can be expected to influence disease dissemination and patient survival. This is consistent with results observed in clinical trials, overviews of which indicate that prevention of four local recurrences will, on the average, prevent one death from breast cancer. Optimisation of local-regional treatment is an important goal in breast cancer management.

Breast Neoplasms↗
PubMed2001

The impact of gap duration on local control in anal canal carcinoma treated by split-course radiotherapy and concomitant chemotherapy.

PURPOSE: To investigate the potential benefit of reducing the intersequence gap in patients with anal cancer treated with split-course chemoradiotherapy. METHODS: The study group consisted of 90 patients with anal squamous carcinoma treated between 1981 and 1998, using concomitant chemotherapy (CT) and radiation (RT). Median age was 65 years (range 41-87). RT was delivered in a split course, with a median gap of 37.5 days (range 4-97) between sequences. First (pelvic) sequence delivered a median dose of 40 Gy (range 36-50.4), using AP/PA megavoltage photon beams. Boost treatment (median dose 20 Gy, range 13-26) consisted of either Iridium-192 implantation (49 patients) or external beam RT (41 patients). CT consisted of 1-2 cycles of a 5-day continuous infusion of 5-fluorouracil and bolus mitomycin C, usually administered during the first week of each RT course. Median follow-up was 76.2 months. Univariate and multivariate analyses were performed to determine the factors associated with locoregional control (LRC). RESULTS: Five-year actuarial LRC was 72.5%. Factors associated with poorer LRC (univariate) were: age < or = 65, male gender, and gap > 37.5 days. Number of CT cycles (1 vs. 2 or more), boost technique (brachytherapy vs. external), and T-stage were not significantly associated with LRC. In multivariate analysis, only age (p = 0.01), and gap (p = 0.02) retained their significance. In patients older than 65 years, LRC was 92.3% and 75% for shorter and longer gaps, respectively. In younger patients, the corresponding values for LRC were 73.7% and 50%. CONCLUSION: In anal cancers, split-course RT with > 50 Gy dose delivery is difficult to avoid because of acute toxicity. The present analysis suggests that shortening the gap contributes to optimizing LRC. Gaps longer than 5 weeks correlated with poorer LRC, with especially unsatisfactory results observed in younger patients.

Adult↗
PubMed2001

Which patients don't need a tumor-bed boost after whole-breast radiotherapy?

BACKGROUND: Retrospective dose-response data suggest that a boost of about 15 Gy to the tumor bed following whole-breast radiotherapy reduces the risk of local recurrence (IBTR) by as much as 2-fold. Even if this benefit is confirmed by prospective trials, boost irradiation may not be considered cost-effective in patients having an IBTR risk of less than 1% per annum. METHODS: Published prospective trials of invasive breast cancers (National Surgical Adjuvant Breast and Bowel Project; Stockholm Adjuvant Tamoxifen Trial) in which patients received 50 Gy whole-breast irradiation, without a boost, were analyzed to identify subgroups with IBTR risk less than 1% per year. All studies were based on lumpectomy (rather than segmental or quadrant excision) and eligibility required the absence of cancer cells at the margins. It was assumed that clinical and pathological factors, other than those defining trial eligibility, were of negligible importance regarding IBTR risk, with the exception of young age. RESULTS: All patients not receiving adjuvant systemic therapy, including tumors < 1 cm, have IBTR risk justifying boost irradiation. Of patients receiving systemic therapy, only patients with node-negative, estrogen receptor-positive tumors have low IBTR risk (3% at 10 years), provided that tamoxifen is administered. Of patients receiving only adjuvant chemotherapy, low IBTR risk seems to be associated with administration concomitantly with radiotherapy. IBTR risk in patients receiving chemotherapy sequentially with respect to radiotherapy probably is high enough to justify a boost. A boost is probably indicated in all patients younger than 40 years, regardless of other factors.

Antineoplastic Agents, Hormonal↗
PubMed2001

Assessment of target dose delivery in anal cancer using in vivo thermoluminescent dosimetry.

PURPOSE: To measure anal dose during external beam radiotherapy (EBRT) using in vivo dosimetry, to study the difference of measured from prescribed dose values, and to evaluate possible associations of such differences with acute and late skin/mucosal toxicity and anorectal function. MATERIALS: Thirty-one patients with localized anal carcinoma underwent in vivo measurements during the first EBRT session. Themoluminescent dosimeters (TLD) were placed at the center of the anal verge according to a localization protocol. No bolus was used. Patients received a median dose of 39.6 Gy (range: 36-45 Gy) by anteroposterior opposed AP/PA pelvic fields with 6 or 18 MV photons, followed by a median boost dose of 20 Gy (range: 13-24 Gy). Concomitant chemotherapy (CCT), consisting of 1-2 cycles of continuous infusion 5-fluorouracil (5-FU) and bolus mitomycin-C (MMC), was usually administered during the first weeks of the pelvic and boost EBRT courses. Acute and late skin/mucosal reactions were recorded according to the Radiation Therapy Oncology Group (RTOG) toxicity scale. Anal sphincter function was assessed using the Memorial Sloan Kettering Cancer Center (MSKCC) scale. RESULTS: TLD anal doses differed by a mean of 5.8% (SD: 5.8) in comparison to the central axis prescribed dose. Differences of at least 10% and at least 15% were observed in eight (26%) and three (9.7%) patients, respectively. TLD doses did not significantly correlate with acute or late grade 2-3 skin or mucosal toxicity. However, patients having good-fair MSKCC anal function had a significantly greater mean difference in anal TLD dose (10.5%, SD: 5.9) than patients having excellent function (3.8%, SD: 4.6) (P = 0.004). Prescribed dose values, length of follow-up, and age at diagnosis did not correlate with late sphincter function. CONCLUSIONS: These data show that AP/PA fields using megavoltage photons deliver adequate dose to the anal verge. However, in about one quarter of patients treated with this technique the anal dose varied from the prescribed dose by at least 10%. The observed correlation of TLD values and late sphincter function suggests that direct measurement of the dose delivered to the anal verge might be clinically relevant.

Adult↗
PubMed2001

Sphincter-conserving treatment of carcinomas of the anal margin.

Between April 1982 and December 1997 24 patients with carcinoma of the anal margin were treated with radiation therapy (RT) (10 patients) or RT-chemotherapy (CT) (14 patients). External beam RT (EBRT) was delivered in 18 patients, combined with brachytherapy in 5 patients, while one patient was treated with brachytherapy alone. Inguinal nodes were irradiated in 17 patients. Chemotherapy was based on 5-fluorouracil and mitomycin-C. At 5 years, the overall survival rate was 56% and the locoregional rate was 69.5%. Anal sphincter was preserved in 16/24 treated patients. Grade 4 late complications were observed in 3 patients. This study reinforces the notion that radical RT +/- CT provides a high probability of cure and sphincter preservation in patients presenting with this rare condition. Major late toxicity is uncommon; a better adaptation of treatment technique to the individual clinical situation may prevent some of the more severe complications in the future.

Adult↗
PubMed2001

The Pregnancy Discrimination Act: employer health insurance plans must cover prescription contraceptives.

The Equal Employment Opportunity Commission (EEOC), which recently took the position that employer health plans are required, in many instances, to cover prescription contraceptives, has issued guidelines to assist employers in complying with the law prohibiting discrimination on the basis of sex and pregnancy. Employers should review these guidelines carefully in relation to their health care plans.

Contraceptives, Oral↗
PubMed2000

Assessment of quality of life in patients treated with accelerated radiotherapy for laryngeal and hypopharyngeal carcinomas.

BACKGROUND: This study was conducted to evaluate quality of life (QOL) and functional outcome in patients with carcinomas of the larynx and hypopharynx treated with accelerated radiotherapy (RT). METHODS: Between January 1991 and September 1996, 21 patients treated with accelerated concomitant boost RT schedule (69.9 Gy in 5. 5 weeks) for laryngeal (n = 10) or hypopharyngeal (n = 11) carcinomas and who remained free of disease at 1-year minimum follow-up were evaluated. The functional outcome was assessed by the subjective Performance Status Scale for Head and Neck cancer (PSSHN) and general QOL by the European Organization for Research and Treatment of Cancer Core QOL questionnaire (EORTC QLQ-C30). The median length of follow-up was 37 months (range, 13 to 75). RESULTS: The PSSHN scores were 89, 84, and 86, respectively, for eating in public, understandability of speech and normalcy of diet (100 = normal function). Significantly lower scores for understandability of speech were observed in patients with advanced and laryngeal carcinomas. Normalcy of diet was affected negatively by the severity of xerostomia. All mean functional scale scores of the EORTC QLQ-C30 module were 20% to 25% below the higher score. Most of these scale scores were significantly affected by the severity of xerostomia. CONCLUSIONS: Patients treated with concomitant boost RT for laryngeal and hypopharyngeal carcinomas appear to have similar QOL and functional outcome to those reported for patients treated with conventional or hyperfractionated RT. As expected, many QOL scales were affected by the severity of xero- stomia.

Activities of Daily Living↗
PubMed2000

Breast conservation in the 21st century.

As breast cancers are diagnosed at increasingly early stages, and there is little biological rationale for mastectomy in most patients, breast conservation is likely to be practised with increased frequency in the future. Newer breast imaging techniques, particularly magnetic resonance imaging (MRI), should contribute to improved pretherapy planning, both aiding in the selection of patients for conservation approaches, and estimating the residual tumour burden following minimally invasive surgical interventions. Image-guided tumour mapping may permit local treatment to be individualised, most importantly allowing definition of subgroups not requiring treatment directed at the whole breast. Moreover, interventional radiology opens new possibilities for focalised treatments, which may come to be employed in the management of small lesions. The increasing use of primary chemo- or chemoendocrine therapy will also tend to favour the option of breast conservation. Functional imaging techniques, including MRI, may prove valuable in the assessment of response to medical therapy, allowing more individualised use of radiotherapy and surgery. Technical progress and the development of biological response modifiers may further improve the therapeutic ratio associated with radiation treatment.

Breast Neoplasms↗
PubMed2000

Sphincter-sparing surgery after preoperative radiotherapy for low rectal cancers: feasibility, oncologic results and quality of life outcomes.

The present study assesses the choice of surgical procedure, oncologic results and quality of life (QOL) outcomes in a retrospective cohort of 53 patients with low-lying rectal cancers (within 6 cm of the anal verge) treated surgically following preoperative radiotherapy (RT, median dose 45Gy) with or without concomitant 5-fluorouracil. QOL was assessed in 23 patients by using two questionnaires developed by the QOL Study Group of the European Organization for Research and Treatment of Cancer: EORTC QLQ-C30 and EORTC QLQ-CR38. After a median interval of 29 days from completion of RT, abdominoperineal resection (APR) was performed in 29 patients (55%), low anterior resection in 23 patients (20 with coloanal anastomosis) and transrectal excision in one patient. The 3-year actuarial overall survival and locoregional control rates were 71.4% and 77.5% respectively, with no differences observed between patients operated by APR or restorative procedures. For all scales of EORTC QLQ-C30 and EORTC QLQ-CR38, no significant differences in median scores were observed between the two surgical groups. Although patients having had APR tended to report a lower body image score (P = 0.12) and more sexual dysfunction in male patients, all APR patients tended to report better physical function, future perspective and global QOL. In conclusion, sphincter-sparing surgery after preoperative RT seems to be feasible, in routine practice, in a significant proportion of low rectal cancers without compromising the oncologic results. However, prospective studies are mandatory to confirm this finding and to clarify the putative QOL advantages of sphincter-conserving approaches.

Aged↗
PubMed1999

Effectiveness of surgical salvage therapy for patients with locally uncontrolled anal carcinoma after sphincter-conserving treatment.

BACKGROUND: Locally persistent or recurrent anal carcinoma represents a clinically significant problem, the management of which remains the subject of some controversy. Although the few current data suggest that radical surgery remains the sole salvage treatment able to provide some chance of cure, some authors have reported disappointingly low success rates. The current study presents the outcome of patients who failed locally after receiving radiotherapy or chemoradiotherapy for anal carcinoma. METHODS: Of 185 consecutive patients treated between January 1976 and December 1996 with sphincter conservation, 42 subsequently presented with local failure, either alone (27 patients) or with regional or distant metastases (15 patients). Nine patients (21%) received supportive care only, 7 patients (17%) received palliative therapy, and 26 patients (62%) underwent potentially curative surgical salvage treatment, including 23 abdominoperineal resections (APR) and 3 local excisions. The median follow-up after local failure for all patients was 21.5 months (range, 1-231 months). RESULTS: With the exception of 2 patients who committed suicide, all patients who did not undergo surgical salvage therapy died of progressive disease. Among 26 patients who received curative treatment, 11 ultimately achieved disease control. The 5-year overall survival rate after the diagnosis of local failure was 28% for all patients and 44.5% for those receiving curative salvage treatment. For the latter group the 5-year actuarial secondary local and locoregional control rates were 53% and 43%, respectively. CONCLUSIONS: Although APR no longer is the first-line treatment of patients with anal carcinoma, it continues to play an essential role in salvage therapy, resulting in ultimate disease control in approximately 50% of patients with isolated local failure. The curative potential of secondary surgical treatment suggests the possible importance of early detection of persistent or recurrent local disease after nonsurgical, sphincter-conserving therapy.

Adult↗
PubMed1999

Avoidance of treatment interruption: an unrecognized benefit of accelerated radiotherapy in oropharyngeal carcinomas?

PURPOSE: To assess the impact of treatment interruption on the potential gain in locoregional control obtained with accelerated radiotherapy (RT) compared with conventionally fractionated RT in patients with oropharyngeal carcinomas. METHODS AND MATERIALS: 152 patients treated with radical RT for oropharyngeal carcinomas between 1979 and 1996 were retrospectively analyzed. According to the American Joint Committee on Cancer (AJCC) staging system, there were 6/30/43/73 stages III/III/IV. Sixty-one patients were treated with a conventional RT schedule (median dose 70 Gy in 35 fractions), and 91 patients with either of two 5/5.5-week accelerated RT schedules (median dose 69.6-69.9 Gy in 41 fractions). Discounting weekends, RT was interrupted for 2 consecutive days or more in 53 patients (median duration 11 days, range 2-97), including 67% of the patients in the conventional RT group and 13% in the accelerated RT group. Median follow-up for surviving patients was 55 months (range 23-230). The Cox proportional hazards model was used for the multivariate analysis of factors influencing locoregional control. RESULTS: In univariate analysis, factors associated with a significant decrease in locoregional control included WHO performance status > or =1, advanced AJCC stages (III and IV), conventional RT fractionation, overall treatment time > or =44 days (median), and RT interruption. In the multivariate analysis, when introduced into the model individually, the three significant therapeutic factors remained significant after adjustment for the forced clinical variables. However, when the three therapeutic factors were introduced together into the model, beside the AJCC stage (P = 0.017), only RT interruption remained a significant independent adverse prognostic factor (P = 0.026). CONCLUSIONS: This multivariate analysis highlights the potential negative impact of treatment gaps on locoregional control in oropharyngeal carcinomas. This suggests that treatment interruption may be an even more important parameter than the type of RT schedule per se. Thus, when assessing the relative merit of two RT schedules, inclusion of the other therapeutic factors in a multivariate model is mandatory in order to avoid misinterpretation of the results.

Adult↗
PubMed1999

Feasibility and tolerance of pulsed dose rate interstitial brachytherapy.

PURPOSE: Pulsed dose rate (PDR) treatment is a new approach that associates the physical advantages of high-dose-rate (HDR) technology with the potential radiobiological advantages of low-dose-rate (LDR) brachytherapy. This retrospective study analyzes the feasibility, toxicity, and preliminary oncologic results in a series of 43 patients treated with PDR interstitial brachytherapy. METHODS AND MATERIALS: Twenty-four patients with pelvic, 17 patients with head and neck, and 2 patients with breast cancers were treated. Twenty-eight patients had primary and 15 recurrent tumors; 14 had received prior external irradiation to the same site. The doses per pulse at the prescription isodose were 0.4-1 Gy (median 0.5 Gy), delivered using a single cable-driven 0.3-1.0 Ci 192-iridium source (PDR Nucletron Micro-Selectron). RESULTS: The median treated volumes (at the prescribed isodose) were 28 cc for pelvic, 8.33 cc for head and neck, and 40 cc for breast malignancies. Of 14,499 source and 14,499 dummy source transfer procedures, 3 technical machine failure events were observed (0.02%). Grade 3 acute toxicities were seen in 5/43 patients (4 oral stomatitis, 1 vaginal mucositis) and grade 4 acute toxicity in one patient (rectovaginal fistula). Grade 3-4 late complications were observed in 4/41 (9.8%) patients: 1 pubic fracture, 1 rectovaginal fistula, 1 vesicovaginal fistula and 1 local necrosis. With a median follow-up of 18 months, 10/41 patients progressed locoregionally (6 pelvic, 4 head and neck), 3 developed local recurrence and distant metastasis (3 pelvic), 3 only distant metastasis (2 pelvic, 1 head and neck). Two patients are lost to follow-up. CONCLUSION: PDR interstitial brachytherapy for pelvic, head and neck, and breast malignancies is feasible and the acute and late toxicities seem acceptable. Although the physical advantages of PDR are clear, further follow-up is required to determine how results compare with those obtained with standard LDR brachytherapy.

Adult↗
PubMed1999

Treatment of anal carcinoma in the elderly: feasibility and outcome of radical radiotherapy with or without concomitant chemotherapy.

BACKGROUND: For most cancers, information on treatment tolerance and results for elderly patients is quite limited. This study was conducted to investigate the feasibility and results of curative nonsurgical treatment of patients age 75 years or older with anal carcinoma. METHODS: From January 1976 through June 1996, invasive anal squamous cell carcinoma was diagnosed in 58 patients age > or = 75 years. Curative treatment was administered to 47 patients (81%), of whom 42 received radiotherapy (RT), either used alone (21) or associated with concomitant chemotherapy (CT). RT was administered in two sequences, the first in which a median dose of 39.6 gray (Gy) was delivered with megavoltage photon beams, followed (after a median interval of 43 days) by a boost with either brachytherapy or external beam (median dose, 20 Gy). CT started on Day 1 and generally consisted of 1 cycle of mitomycin C (MMC; median dose, 9.5 mg/m2) and a 96-hour infusion of 5-fluorouracil (5-FU; median dose, 600 mg/m2/day). The median follow-up for all patients was 48 months (range, 5-163 months). RESULTS: Of 40 patients (95%) who completed curative treatment, acute toxicity resulted in shortening of the planned first irradiation sequence in 2 patients (1 in each group) and an unplanned treatment break in 11 patients (4 in the RT group and 7 in the RT-CT group). Grade 2 and 3 acute reactions (RTOG) were observed in 43% and 54% of patients, respectively. Among all Grade 3 reactions, 32% occurred in the RT group and 68% in the RT-CT group. In patients receiving RT-CT, Grade 2-3 leukopenia was observed in 25% of patients, Grade 2-3 fatigue was observed in 58% of patients, and Grade 2 cardiac toxicity related to 5-FU occurred in 1 patient. At 5 years, the overall survival was 54% (49% and 59% for the RT and RT-CT groups, respectively, P = 0.28), and the actuarial local control rate was 78.5% (73% and 83% for the RT and RT-CT groups, respectively, P=0.36). Five patients presented with Grade 3-4 late complications, all of them in the RT-CT group. CONCLUSIONS: The current series confirms the feasibility of sphincter-conserving treatment for elderly patients who present with anal carcinoma. Rates of acute or late complications appeared similar to those observed in younger patients, and the oncologic results were at least as favorable as those commonly reported.

Aged↗
PubMed1999

A conservation approach to pharyngeal carcinoma with advanced neck disease: optimizing neck management.

BACKGROUND: Surgical management of advanced neck disease remains controversial when a conservative approach based on radiotherapy is retained for primary tumors. The objective of this study was to evaluate retrospectively treatment results in pharyngeal cancers presenting with N2-N3 neck disease, using neck dissection followed by radical locoregional radiotherapy (RT) and to compare these results with those obtained in patients treated by radical RT alone. METHODS: From August 1991 to November 1996, 41 patients with carcinomas of the oro- or hypopharynx were staged as T1-T3 N2-N3 M0 (American Joint Committee on Cancer [AJCC] stage IV). Twenty-four patients were treated with neck dissection followed by RT (group 1) and 17 patients with radical RT (group 2) using a progressively accelerated concomitant boost schedule. Chemotherapy was delivered to 6 patients in group 1 and 8 in group 2 partially concomitantly with RT. RESULTS: Three-year actuarial locoregional control was 73% and 55% for groups 1 and 2, respectively (p = .52). The corresponding 3-year actuarial overall survival rates were 37% and 50% (p = .42). Severe postoperative complications were observed after neck dissection in four patients (16%). Acute toxicity during RT was similar in the two groups. Late toxicities were also similar, except for two patients in group 1 who developed severe laryngeal edema. CONCLUSIONS: Neck dissection followed by radical RT to the primary tumor and neck represents a valid treatment option in this subset of patients, allowing good control of advanced neck disease, while at the same time conserving pharyngolaryngeal function. However, for patients who are at high risk of severe postoperative complications, radical RT can be considered a worthy alternative, particularly for oropharyngeal carcinomas.

Carcinoma, Squamous Cell↗