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T Wasserman

Publications and source records attributed to T Wasserman.

At least 19 recordsLinked to original sources
PubMed2026

Outcomes of elacestrant in patients with ER-positive, HER2-negative, ESR1-mutated metastatic breast cancer who received prior endocrine therapy and cyclin-dependent kinase inhibitor in a real-world setting.

BACKGROUND: Real-world data analyses show durable benefits with elacestrant, with or without prior treatment with cyclin-dependent kinase 4/6 inhibitor (CDK4/6i). This cohort focused on patients with ER-positive/HER2-negative estrogen receptor 1 (ESR1)-mutated metastatic breast cancer (mBC) treated with elacestrant after at least one line of endocrine therapy (ET) combined with CDK4/6i (N = 281). PATIENTS AND METHODS: Claims data from the Komodo Research Dataset linked with Foundation Medicine clinical-genomics data were used. Primary outcome was median time-to-next-treatment (mTTNT). RESULTS: In patients with ER-positive/HER2-negative ESR1-mutated mBC who received one to two prior lines of ET + CDK4/6i (n = 108), mTTNT with elacestrant was 8.2 months [95% confidence interval (CI) 6.0-12.2]. In patients who received one to two prior lines of ET + CDK4/6i for ≥12 months (n = 85), mTTNT was 9.0 months (95% CI 7.7-13.7), including an mTTNT of 12.2 months (95% CI 9.0-not reached) in those who received one prior line of ET (n = 31). In patients with liver and/or lung metastasis (n = 169), mTTNT was 6.9 months (95% CI 5.8-8.3), whereas it was 7.4 months (95% CI 5.6-12.9) in patients with brain metastasis (n = 68). In patients with coexisting ESR1- and phosphoinositide 3-kinase-pathway-mutated tumors (n = 115), mTTNT was 6.1 months (95% CI 5.0-8.1). CONCLUSIONS: Elacestrant showed durable benefits in patients with ER-positive/HER2-negative ESR1-mutated mBC previously exposed to at least one line of ET + CDK4/6i, reinforcing the role of elacestrant as a potential first-choice option for patients with endocrine-sensitive tumors.

ESR1 mutation↗
PubMed1999

Radioprotective effects of amifostine.

Effective radiotherapy for patients with cancer should include maximal tumor cell killing with minimal injury to normal tissue. However, current radiation doses that can be delivered without causing severe damage to surrounding normal tissues are often insufficient to eradicate a tumor. Recently, a number of agents have been developed to protect normal tissue from the harmful effects of antitumor therapies. The aminothiol amifostine (Ethyol; Alza Pharmaceuticals, Palo Alto, CA/US Bioscience, West Conshohocken, PA) has been the subject of extensive research as a prospective protector. While this drug has been approved for use to reduce toxicities associated with cisplatin, several studies also have demonstrated that amifostine protects normal tissues from both acute and late radiation damage without protecting the tumor. Consequently, higher radiation doses could be used with less than or equal risk to surrounding normal tissues. This report reviews the physicochemical basis of radiation therapy on biologic tissues and the mechanisms responsible for the cytoprotective effects of amifostine. The increasing body of biochemical, preclinical, and clinical data could justify the use of protectors such as amifostine with radiotherapy to provide improved therapeutic efficacy and quality of life for the patient.

Amifostine↗
PubMed1997

When is a negative study not negative?

Results of Phase III randomized clinical trials can be categorized into three groups: positive, null, and negative. The jargon used in discussing results of comparative studies requires clarification because misclassification can result in incorrect interpretation. A positive result indicates that the experimental therapy(ies) is(are) superior to standard therapy. A null result indicates that no statistically significant difference between therapies was found; hence, standard therapy should not be replaced. A negative result indicates that the experimental therapy had a deleterious effect compared to standard therapy. This article presents a discussion of these categories and examples of each.

Clinical Trials, Phase III as Topic↗
PubMed1997

Recursive partitioning analysis (RPA) of prognostic factors in three Radiation Therapy Oncology Group (RTOG) brain metastases trials.

PURPOSE: Promising results from new approaches such as radiosurgery or stereotactic surgery of brain metastases have recently been reported. Are these results due to the therapy alone or can the results be attributed in part to patient selection? An analysis of tumor/patient characteristics and treatment variables in previous Radiation Therapy Oncology Group (RTOG) brain metastases studies was considered necessary to fully evaluate the benefit of these new interventions. METHODS AND MATERIALS: The database included 1200 patients from three consecutive RTOG trials conducted between 1979 and 1993, which tested several different dose fractionation schemes and radiation sensitizers. Using recursive partitioning analysis (RPA), a statistical methodology which creates a regression tree according to prognostic significance, eighteen pretreatment characteristics and three treatment-related variables were analyzed. RESULTS: According to the RPA tree the best survival (median: 7.1 months) was observed in patients < 65 years of age with a Karnofsky Performance Status (KPS) of at least 70, and a controlled primary tumor with the brain the only site of metastases. The worst survival (median: 2.3 months) was seen in patients with a KPS less than 70. All other patients had relatively minor differences in observed survival, with a median of 4.2 months. CONCLUSIONS: Based on this analysis, we suggest the following three classes: Class 1: patients with KPS > or = 70, < 65 years of age with controlled primary and no extracranial metastases; Class 3: KPS < 70; Class 2- all others. Using these classes or stages, new treatment techniques can be tested on homogeneous patient groups.

Adult↗
PubMed1997

The perception of sexual attractiveness: sex differences in variability.

Results of three independent studies supported predictions derived from evolutionary theory: Men's assessments of sexual attractiveness are determined more by objectively assessable physical attributes; women's assessments are more influenced by perceived ability and willingness to invest (e.g., partners' social status, potential interest in them). Consequently, women's assessments of potential partners' sexual attractiveness and coital acceptability vary more than men's assessments. The proposition that polygamous women's assessments of men's sexual attractiveness vary less than those of monogamous women (because the former allegedly are more influenced by target persons' physical attributes) was also tested. In Study 1 male college students showed more agreement than females in their rankings of the sexual attractiveness of opposite-sex target persons. Target persons' flesh and bodily display enhanced this sex difference. In Study 2 men exhibited less variance than did women in their ratings of target persons' acceptability for dating and sexual relations. Women who viewed models described as having low status showed more variability than did women in the high-status condition. In Study 3 women showed more variability than men did in their ratings of 20 opposite-sex celebrities' sexual attractiveness. Studies 2 and 3 included the Sociosexual Orientation Inventory (SOI)-a measure of polygamous attitudes and behavior. Women's SOI scores did not affect the variability of their assessments in either Study 2 or 3. In Study 3 men with low SOI scores showed less variability than did men with high SOI scores. Alternative explanations of the findings are examined. Theoretical and empirical implications are discussed.

Adolescent↗
PubMed1995

Pathophysiology of irradiated skin and breast.

The evolution, time course, and dose response of gross and histologic changes associated with the acute and late changes of the skin are noted and a composite pathophysiologic operational model given. This model focuses the selection of the observations to be "scored" to assess the tolerance and cosmetic response of the skin and breast to different dose and combined therapy studies. Skin scoring, Late effects skin, Late effects breast, Skin irradiation response, Breast radiation response, Pathophysiology of irradiated skin, Dose tolerance of skin, Dose tolerance of breast, Skin functional unit, Microvessel response to irradiation.

Animals↗
PubMed1995

The impact on quality of life by radiation late effects.

The Radiation Therapy Oncology Group (RTOG) is developing an improved scoring system for the late effects of radiation therapy. There is a need to assess the impact of treatment on long-term survival. The RTOG Late Effects Toxicity Grading Scale documents the absence or the degree to which a symptom or sign is present. The scale in itself does not, however, score the impact of symptoms on survival. This Late Effects Scale in conjunction with quality-of-life assessments will provide the information necessary to assess the impact of treatment toxicities on normal daily living. Neither documentation of late effects nor their impact on quality of survival is an end in itself. These scales are only instruments that should serve to direct us toward our higher goal of designing interventional studies concerned with the quality of survival or rehabilitation. The development of the Late Effects Toxicities Grading Scale is a beginning.

Goals↗
PubMed1995

Clinical introduction of a commercial treatment chair to facilitate thorax irradiation.

There are occasions when patients can benefit significantly from being treated upright. This technique is beneficial in the treatment of Hodgkin's disease when the mediastinum is involved. The main benefit is the lung volume spared resulting from narrowing of a bulky mediastinum. We purchased a commercial treatment chair to facilitate upright treatment. Clinical implementation required rigorous testing, documentation of procedures, and acknowledgment of and corresponding solutions to limitations. The purchased chair is designed to couple with the spine bar of the treatment couch, allowing patient positioning via pendant functions. The chair has no obstruction as immobilization is afforded by arm, shoulder, and knee supports, which allows isocentric treatments. An additional hydraulic mount is used for simulation. We have treated five patients thus far, including Hodgkin's disease patients with and without mediastinal involvement, and one lung cancer patient with a large lower lobe lesion. All patients have benefited by having a greater volume of lung spared (as much as 60% additional blocking) when upright simulation films are compared with supine and prone films. Immobilization has been adequate as confirmed by daily light field projections and portal films. We are routinely evaluating Hodgkin's disease patients for upright treatment. Patients treated in the chair have benefited in terms of lung volume spared without loss of immobilization. A patient with a large lower lobe lung lesion has also benefited as the tumor "dropped," thus affording lung sparing via blocking.

Equipment Design↗
PubMed1993

Iododeoxyuridine (IUdR) combined with radiation in the treatment of malignant glioma: a comparison of short versus long intravenous dose schedules (RTOG 86-12).

PURPOSE: To evaluate the toxicity and tumor efficacy of the halopyrimidine IUdR (NSC #39661, IND 22475) as a chemical modifier of radiation response when used in a high dose short time infusion versus the acceptable 4 day infusion. METHODS AND MATERIALS: In August 1987 we initiated a prospective study in patients with newly diagnosed anaplastic astrocytoma and glioblastoma. The study was designed to have a fixed dose of radiation (60.16 Gy = 1.88 Gy in 32 fractions in 6.5 weeks) but varying the dose schedule of IUdR, keeping the total dose between 21 and 24 g/m2. IUdR was delivered in a 96, 48, or 24 hr continuous intravenous infusion per week for 6.5 weeks during radiation treatment. RESULTS: The study was closed for patient accrual on October 1, 1991. Twenty-two patients were treated on the 96 hrs, 32 on the 48 hr and 25 on the 24 hr schedules. The incidence of glioblastoma ranged between 68 and 75% in the three arms. Seventy percent of the patients had a Karnofsky of 80-90% at the onset of treatment. Over 50% of the patient population were under age 55. Drug tolerance was related to the duration of the IUdR infusion. Toxicities were most pronounced in the 96 hr IUdR infusion schedule where 27.4% of the patients reported a grade 3 drug toxicity. No fatal or grade 4 toxicities were observed. More patients on the 24 and 48 hr schedule received at least 80% of the IUdR dose specified per protocol. We did not observe a trend in acute normal tissue radiation reactions in any of the three arms. The median survivals calculated from the Kaplan-Meier plot are 13.4, 10.5, and 11 months, respectively, for the 96, 48, and 24 hr infusions. The Cox Proportional Hazards model showed that any difference in survival can be attributed to histological grade, type of previous surgery and, to some extent, age of the patient. Dose schedule was not a significant predictor of survival, although statistically nonsignificant trend toward longer survival is seen in those patients with glioblastoma treated in the "long" 4 day schedule. CONCLUSION: Overall, our treatment combination, particularly for patients with glioblastoma, has not shown convincing evidence of an improvement in survival. Of interest, however, it is the 2 year survival rate of 68% for patients with anaplastic astrocytoma. In our experience, the administration of IUdR is laborious, time consuming and with bothersome acute gastrointestinal and hematological toxicities.

Adolescent↗
PubMed1989

The role of hemoglobin concentration in the outcome of misonidazole-sensitized radiotherapy of head and neck cancers: based on RTOG trial #79-15.

Recent data from the DAHANCA (Danish Head and Neck Cancer) 2 study implies a positive effect of high hemoglobin concentration in concert with misonidazole for the treatment of head and neck cancers by radiotherapy. We have therefore reviewed and updated our analysis of RTOG protocol 79-15, which included the effect of misonidazole plus radiotherapy in a presumably similar population. Despite additional follow-up and more sophisticated analysis, our analysis does not demonstrate an influence of hemoglobin concentration on any of the outcome measures we examined. Possible explanations for the difference in findings of RTOG 79-15 and DAHANCA 2 are discussed. Radiation therapy of head and neck squamous cancers, Hypoxia and hemoglobin conc. in head and neck cancers, Oral cavity cancer, Effect of radiation therapy, Oropharynx cancer, Hemoglobin and radiotherapy, Hemoglobin concentration, Effect upon radiotherapy, Irradiation of oropharynx cancer, Hgb effect.

Carcinoma, Squamous Cell↗
PubMed1987

Radiotherapy with or without misonidazole for patients with stage IIIB or stage IVA squamous cell carcinoma of the uterine cervix: preliminary report of a Radiation Therapy Oncology Group randomized trial.

Between August 1980 and November 1984, 119 patients with FIGO Stage IIIB or IVA squamous cell carcinoma of the uterine cervix were randomized to receive radiation therapy (4600 cGy pelvis plus 1000 cGy parametrial boost) followed by intracavitary or external boost to the primary with or without misonidazole (MISO) (400 mg/m2 daily 2 to 4 hours prior to radiation therapy). Patients in the two treatment groups were evenly distributed with respect to stratification variables including stage, Karnofsky Performance score, and positivity of para-aortic nodes. Eighty-nine percent of patients had Stage IIIB disease and 88% had a Karnofsky score of 80 or better. Seventy-five percent of patients treated with radiation therapy alone and 79% of patients treated with radiation therapy plus MISO received a boost via intracavitary application. Life threatening (Grade 4) complications occurred in 5 patients receiving radiation therapy alone and one patient receiving radiation therapy plus MISO. MISO toxicity (Grade 3) was limited to severe nausea and vomiting in two patients. With 119 evaluable patients and a median follow-up of 33 months, 64% of patients receiving radiation therapy alone are alive at 18 months compared with 54% for patients assigned to radiation therapy plus MISO. The median survival for patients treated with radiation therapy alone and radiation therapy plus MISO was 1.9 years and 1.6 respectively. At this point in the study the difference in survival is inconsistent with the hypothesis of an improvement associated with MISO. There have been 23 deaths among the 49 patients treated with radiation therapy plus MISO who have been followed for at least 18 months compared with 17 deaths in 48 patients treated with radiation therapy alone. The chance of observing this number of deaths with radiation therapy plus MISO if the addition of MISO improves survival by 10 to 20% is 0.003 and less than 0.001, respectively. The addition of MISO to radiation failed to improve survival for these patients. The results cannot be explained by an uncharacteristically high survival on the radiation therapy alone arm or by an imbalance in the distribution of prognostic factors. Local-regional control remains a problem in the management of patients with advanced cervical carcinoma. More effective and less toxic radiosensitizing agents are needed.

Adolescent↗
PubMed1987

Failure of misonidazole-sensitized radiotherapy to impact upon outcome among stage III-IV squamous cancers of the head and neck.

As part of the RTOG research effort in the treatment of advanced, inoperable squamous cancer of the head and neck region, the hypoxic cell sensitizer, misonidazole, was selected for investigation as an adjuvant to definitive irradiation. Based upon a pilot experience (78-02) showing a 67% complete response rate among 36 AJC Stage III-IV patients receiving full-dose irradiation and 6 weekly p.o. doses of misonidazole, a phase III trial was carried out from '79-'83. Three hundred and six patients were entered, 42% of whom had oropharyngeal primaries and with 78% of all cases representing T3 or T4 (inoperable) lesions. Only 16% of the entire series presented with N0 necks. Fractionation was altered among the misonidazole-receiving patients, in contrast to "standard" 5 treatments per week among "control" patients, such that 2 separate treatments were given on each day of p.o. misonidazole administration (2.0 gm/m2/wk X 6 doses, 2.5 Gy in a.m., 2.1 Gy in p.m.). Total tumor doses were identical among the two treatment arms except that a limitation of 40.0 Gy to spinal cord was specified for sensitized radiotherapy vs. 45.0 Gy for "control" patients. Primary tumor clearance was observed to be 55-60%, with minor variations according to tumor stage and site. The local regional control rate among radiotherapy-alone patients was 26% at 2 years compared to 22% (2 years) within the misonidazole-receiving group. Analysis of survival revealed no advantage to the sensitized patients, with 55 +/- 2% surviving 1 year and 22 +/- 1% living 3 years following treatment in both treatment categories. Distant metastases as first site of failure (12-13%) and the local failure among initial complete responders (46%) showed no advantage to the misonidazole group. Although a misonidazole dosage of 2.0 gm/m2/wk X 6 (12 gm/m2 total) is well tolerated, no clinical benefit was demonstrated in this randomized trial. Other nitroimidazole analogs (e.g. SR-2508) are now being investigated.

Aged↗
PubMed1987

Palliation of advanced pelvic malignant disease with large fraction pelvic radiation and misonidazole: final report of RTOG phase I/II study.

Between October 1979 and June 1982 forty-six patients were entered on a non-randomized Phase I-II protocol for the evaluation of Misonidazole combined with high dose per fraction radiation for the treatment of advanced pelvic malignancies. Pelvic radiation consisted of 1000 cGy in one fraction repeated at 4-week intervals for a total of three treatments. Oral Misonidazole at a dose of 4 gm/m2 was administered 4-6 hr prior to radiation (total dose 12 g/m2). The distribution of histology consisted of 20 gynecologic, 24 bowel, and 2 prostate malignancies. Of the thirty-seven patients completing the three treatments; there were 6 complete responses (14% CR), 10 partial responses (27% PR) 19 minimal or no response (32% NR), and 4 unevaluable. One patient remains NED 5.5 years following radiation. Toxicity directly related to Misonidazole was minimal and consisted primarily of transcient Grade 1, 2 peripheral neuropathy (20% Grade 1, 4% Grade 2) and Grade 2 ototoxicity (4%). Radiation toxicity was significant for late bowel damage. There were 4 (11%) Grade 3 and 7 (19%) Grade 4 gastro-intestinal (GI) toxicities. Kaplan-Meier plot of GI toxicity showed a progressive increase in incidence with time for projected rate of 49% Grade 3, 4 by 12-month. GI toxicity (Grade 3, 4) was also related to tumor response. The complication rate was 80% (4/6) for CR, 30% (3/10) for PR and 26% (5/19) for NR or progression. Because of the GI complication rate, this protocol for palliation of advanced pelvic malignancies has been replaced by a protocol that uses 4 fractions over 2 days (b.i.d.) of 370 cGy per fraction repeated at 3-week intervals for a total of 3 courses.

Combined Modality Therapy↗
PubMed1986

Effect of misonidazole dose on survival in patients with stage IIIB-IVA squamous cell carcinoma of the uterine cervix: an RTOG randomized trial.

Between August 1980 and November 1984, 120 patients with FIGO Stage IIIB or IVA squamous cell carcinoma of the uterine cervix were randomized to receive radiation therapy (RT) (46 Gy pelvis + 10 Gy parametrial boost) followed by intracavitary or external boost to the primary +/- misonidazole (MISO) (400 mg/M2 2-4 hours prior to RT daily, maximum 12 gm/M2). The median at 24-28 hr misonidazole plasma level was 20 micrograms/ml 2-6 hr and 3.5 micrograms/ml. Approximately 60% of the patients on RT + MISO received 100% of expected total Misonidazole dose; peripheral neurologic toxicity was reported for nine patients receiving misonidazole (8 with mild and 1 with moderate paresthesia or pain). Time-dependent regression analyses found that actual cumulative misonidazole dose was not related to duration of survival from start of treatment (p = 0.5). MISO dose expressed as a percent of expected dose was marginally related to increased survival measured from 14 weeks on on study (p = 0.1). No improvement in survival was observed with the addition of misonidazole to RT (64% of the patients on RT alone were alive at 18 months versus 54% of those on RT + MISO).

Carcinoma, Squamous Cell↗
PubMed1984

Is misonidazole neurotoxicity altered by the use of phenytoin and/or dexamethasone in RTOG 79-18 and RTOG 79-16?

An analysis of Misonidazole (MISO) neurotoxicity in RTOG 79-16 and RTOG 79-18 was undertaken to evaluate the incidence of neurotoxicity relative to dexamethasone dose and phenytoin use. MISO was administered as follows: 79-16 arm A, 1 gm/m2 5 days a week for a total of 10 gm/m2 in 2 weeks; 79-16 arm B, 2 gm/m2 twice weekly for a total of 12 gm/m2 in 3 weeks; and 79-18, 2.5 gm/m2 once a week for a total of 15 gm/m2 in 6 weeks. Practically all patients were on dexamethasone, and 240 out of 550 were on phenytoin for seizures. CNS toxicity and ototoxicity rates were no different between treatment groups with overall rates of 2.7 and 1.1%, respectively. Peripheral neuropathy (PN) was 5.1% in 79-16 arm A, 5.9% in 79-16 arm B, and 8.7% in 79-18. Phenytoin did not significantly alter CNS and PN toxicity rates. All ototoxicities occurred in patients not on phenytoin. There was no correlation between dexamethasone dose and incidence of neurotoxicity within each study. However, the incidence of (PN) for the combined studies was 6.4% (35/550) which is lower than 18.9% (85/449) for non-brain Phase III protocols where patients are rarely, if ever, on dexamethasone or other corticosteroids. Four hour and 24 hour plasma MISO levels, and 24 hour/4 hour MISO ratios did not correlate with toxicity.

Brain Neoplasms↗
PubMed1983

A randomized comparison of misonidazole sensitized radiotherapy plus BCNU and radiotherapy plus BCNU for treatment of malignant glioma after surgery; preliminary results of an RTOG study.

A randomized prospective study was performed to evaluate misonidazole radiosensitized radiation therapy in the treatment of malignant glioma. The control arm, Group A, consisted of conventional radiation therapy (6000 cGy/6-7 weeks) to the whole brain plus BCNU (80 mg/m2 on day 3, 4, 5, and then repeated q 8 weeks for 2 years). The BCNU schedule was identical in both arms. In the experimental arm, Group B, misonidazole 2.5 gm/m2 was given once a week for six weeks, to a total dose of 15 gm/m2. It was given orally four hours prior to 400 cGy on Mondays. On Tuesdays, Thursdays and Fridays, 150 cGy was delivered to a total of 5100 cGy/6 weeks. An additional 900 cGy/5F/1 week was given without misonidazole. Patients were stratified according to the prognostic factors of age, performance status, and histology. Distribution of these characteristics among the treatment groups was comparable. As of March 1, 1982, 245 patients were randomized with follow-up information available on 202 patients. The median follow-up is 12 months (range 3-39 months). There is no significant difference in the survival of the two groups. The median survival for Group A was 12.6, and for Group B, 10.7 months. Misonidazole toxicity included an 11% peripheral neuropathy and a 3% central nervous system toxicity. BCNU toxicity included severe hematologic toxicity in 25%, including one death, and significant pulmonary toxicity in 6 out of 55 patients who received a minimum total dose of 960 mg/m2 of BCNU.

Adolescent↗