Benjamin W. Corn

Common toxicity criteria: version 2.0. an improved reference for grading the acute effects of cancer treatment: impact on radiotherapy

In 1997, the National Cancer Institute (NCI) led an effort to revise and expand the Common Toxicity Criteria (CTC) with the goal of integrating systemic agent, radiation, and surgical criteria into a comprehensive and standardized system. Representatives from the Radiation Therapy Oncology Group (RTOG) participated in this process in an effort to improve acute radiation related criteria and to achieve better clarity and consistency among modalities. CTC v. 2.0 replaces the previous NCI CTC and the RTOG Acute Radiation Morbidity Scoring Criteria and includes more than 260 individual adverse events with more than 100 of these applicable to acute radiation effects. One of the advantages of the revised criteria for radiation oncology is the opportunity to grade acute radiation effects not adequately captured under the previous RTOG system. A pilot study conducted by the RTOG indicated the new criteria are indeed more comprehensive and were preferred by research associates. CTC v. 2.0 represents an improvement in the evaluation and grading of acute toxicity for all modalities.

Edema associated with I-125 or Pd-103 prostate brachytherapy and its impact on post-implant dosimetry: an analysis based on serial CT acquisition

PURPOSEnTo characterize the magnitude and duration of post-implant edema following the implantation of I-125 or Pd-103 seeds into the prostate and to investigate its effect on the CT-based calculation of the total dose delivered by the implant.nnnMATERIALS AND METHODSnA pre-implant CT scan and 3 to 5 serial post-implant CT scans were obtained on 10 patients who received either I-125 or Pd-103 seed implants. None of the patients received hormone therapy. The magnitude and duration of edema were determined from the change in the spatial distribution of the implanted seeds as the edema resolves. Dose volume histograms were compiled to determine the percentage of the prostate volume that received a dose equal to, or greater than, the prescribed dose.nnnRESULTSnThe magnitude of the edema, expressed as the ratio of the post- to pre-implant volume on the day of the procedure, ranged from 1.33 to 1.96 (mean 1.52). The edema decreased exponentially with time; however, the edema half-life (time for the edema to decrease by 1/2) varied from 4 to 25 days (mean 9.3 days). As the edema resolved, the percentage of the prostate that received a dose equal to or greater than the prescribed dose increased by at least 7% in 7 of the 10 patients and increased by more than 15% in 2. In those patients in whom dose coverage was unaffected by the resolution of edema, more than 90% of the prostate was covered by the prescribed dose in the initial CT scan.nnnCONCLUSIONnPost-implant edema increased the prostate volume by factors which ranged from 1.33 to 1.96 (mean: 1.52). The edema resolved exponentially with an edema half-life which varied from 4 to 25 days (mean: 9.3 days). Edema had a significant effect on the post-implant dosimetry in 7 of 10 cases. Factors that affect the impact of edema on the dosimetry are the magnitude of the edema and the planned margin between the prescribed isodose line and the periphery of the prostate.

Stereotactic radiosurgery and fractionated stereotactic radiotherapy for the treatment of acoustic schwannomas: comparative observations of 125 patients treated at one institution

BACKGROUNDnStereotactic radiosurgery (SRS) and, more recently, fractionated stereotactic radiotherapy (SRT) have been recognized as noninvasive alternatives to surgery for the treatment of acoustic schwannomas. We review our experience of acoustic tumor treatments at one institution using a gamma knife for SRS and the first commercial world installation of a dedicated linac for SRT.nnnMETHODSnPatients were treated with SRS on the gamma knife or SRT on the linac from October 1994 through August 2000. Gamma knife technique involved a fixed-frame multiple shot/high conformality single treatment, whereas linac technique involved daily conventional fraction treatments involving a relocatable frame, fewer isocenters, and high conformality established by noncoplanar arc beam shaping and differential beam weighting.nnnRESULTSnSixty-nine patients were treated on the gamma knife, and 56 patients were treated on the linac, with 1 NF-2 patient common to both units. Three patients were lost to follow-up, and in the remaining 122 patients, mean follow-up was 119 +/- 67 weeks for SRS patients and 115 +/- 96 weeks for SRT patients. Tumor control rates were high (> or =97%) for sporadic tumors in both groups but lower for NF-2 tumors in the SRT group. Cranial nerve morbidities were comparably low in both groups, with the exception of functional hearing preservation, which was 2.5-fold higher in patients who received conventional fraction SRT.nnnCONCLUSIONnSRS and SRT represent comparable noninvasive treatments for acoustic schwannomas in both sporadic and NF-2 patient groups. At 1-year follow-up, a significantly higher rate of serviceable hearing preservation was achieved in SRT sporadic tumor patients and may therefore be preferable to alternatives including surgery, SRS, or possibly observation in patients with serviceable hearing.

Will primary central nervous system lymphoma be the most frequent brain tumor diagnosed in the year 2000

There has been a dramatic increase in the diagnosis of primary lymphoma of the brain during the past decade, prompting speculation that it may become the most frequently diagnosed tumor of the central nervous system by the year 2000. The current analysis drew from the updated Surveillance, Epidemiology, and End Results (SEER) database to establish projections for the incidence of brain lymphoma. The study also attempted to determine whether increased incidence rates are attributable to the increasing incidence of acquired immunodeficiency syndrome (AIDS) and whether there is gender or age dependence.

Vaginal stenosis and sexual function following intracavitary radiation for the treatment of cervical and endometrial carcinoma

PURPOSEnThis study was designed to document the incidence and degree of vaginal stenosis, sexual activity, and satisfaction in women treated with intracavitary radiation therapy for cervical or endometrial carcinoma.nnnMETHODS AND MATERIALSnThe incidence of vaginal stenosis in 90 patients treated for either cervical carcinoma (n = 42) or endometrial carcinoma (n = 48) with standard doses of intracavitary radiation from 1989 to 1992 with at least 6 months follow-up was recorded. Vaginal length was measured using a modified vaginal dilator calibrated in centimeters. Semistructured patient interviews documented pretreatment and posttreatment sexual activity and sexual satisfaction.nnnRESULTSnVaginal length was found to be dependent on diagnosis (cervical vs. endometrial), stage (I vs. II/III), and follow-up interval (6-12 months, 12-24 months, and > 24 months). Slightly more women reported sexual activity post vs. pretreatment (31% active pretreatment vs. 43% active posttreatment). However, 22% of women reported a decrease in sexual frequency and 37% reported a decrease in sexual satisfaction. Reports for all parameters were worse for women treated for cervical carcinoma vs. women treated for endometrial carcinoma with the exception of dyspareunia.nnnCONCLUSIONnHigh-dose radiation for either cervical or endometrial carcinoma at standard doses with or without hysterectomy can cause a decrease in vaginal length as compared to the normal vaginal length of 8 to 9 cm documented by Masters and Johnson. Women treated with intracavitary implants remained as sexually active postimplant as preimplant, however, coital frequency and sexual satisfaction decreased while dyspareunia increased. The decrease in vaginal length may explain in part the decrease in sexual satisfaction but cause and effect have not been established.

A phase I dose escalation study of hypofractionated stereotactic radiotherapy as salvage therapy for persistent or recurrent malignant glioma

PURPOSEnA phase I dose escalation of hypofractionated stereotactic radiotherapy (H-SRT) in recurrent or persistent malignant gliomas as a means of increasing the biologically effective dose and decreasing the high rate of reoperation due to toxicity associated with single-fraction stereotactic radiosurgery (SRS) and brachytherapy.nnnMATERIALS AND METHODSnFrom November 1994 to September 1996, 25 lesions in 20 patients with clinical and/or imaging evidence of malignant glioma persistence or recurrence received salvage H-SRT. Nineteen patients at the time of initial diagnosis had glioblastoma multiforme (GBM) and one patient had an anaplastic astrocytoma. All of these patients with tumor persistence or recurrence had received initial fractionated radiation therapy (RT) with a mean and median dose of 60 Gy (44.0-72.0 Gy). The median time from completion of initial RT to H-SRT was 3.1 months (0.7-45.5 months). Salvage H-SRT was delivered using daily 3.0-3.5 Gy fractions (fxs). Three different total dose levels were sequentially evaluated: 24.0 Gy/3.0 Gy fxs (five lesions), 30.0 Gy/3.0 Gy fxs (10 lesions), and 35.0 Gy/3.5 Gy fxs (nine lesions). Median treated tumor volume measured 12.66 cc (0.89-47.5 cc). The median ratio of prescription volume to tumor volume was 2.8 (1.4-5.0). Toxicity was judged by RTOG criteria. Response was determined by clinical neurologic improvement, a decrease in steroid dose without clinical deterioration, and/or radiologic imaging.nnnRESULTSnNo grade 3 toxicities were observed and no reoperation due to toxicity was required. At the time of analysis, 13 of 20 patients had died. The median survival time from the completion of H-SRT is 10.5 months with a 1-year survival rate of 20%. Neurological improvement was found in 45% of patients. Decreased steroid requirements occurred in 60% of patients. Minor imaging response was noted in 22% of patients. Using Fishers exact test, response of any kind correlated strongly to total dose (p = 0.0056). None of six lesions treated with 21 Gy or 24 Gy responded, whereas there was a 79% response rate among the 19 lesions treated with 30 or 35 Gy. Tumor volumes < or =20 cc were associated with a higher likelihood of response (p = 0.053).nnnCONCLUSIONSnH-SRT used in this cohort of previously irradiated patients with malignant glioma was not associated with the need for reoperation due to toxicity or grade 3 toxicity. This low toxicity profile and encouraging H-SRT dose-related response outcome justifies further evaluation and dose escalation.

Management of extremity soft tissue sarcomas with limbsparing surgery and postoperative irradiation: Do total dose, overall treatment time, and the surgery-radiotherapy interval impact on local control?

PURPOSEnTo evaluate potential prognostic factors in the treatment of extremity soft tissue sarcomas that may influence local control, distant metastases, and overall survival.nnnMETHODS AND MATERIALSnSixty-seven patients with extremity soft tissue sarcomas were treated with curative intent by limb-sparing surgery and postoperative radiation therapy at the Fox Chase Cancer Center or the Hospital of the University of Pennsylvania, between October 1970 and March 1991. Follow-up ranged from 4-218 months. The median external beam dose was 60.4 Gy. In 13 patients, interstitial brachytherapy was used as a component of treatment.nnnRESULTSnThe 5-year local control rate for all patients was 87%. The 5-year local control rate for patients who received < or = 62.5 Gy was 78% compared to 95% for patients who received > 62.5 Gy had larger tumors (p = 0.008) and a higher percentage of Grade 3 tumors and positive margins than patients who received < or = 62.5 Gy. The 5-year local control rate for patients with negative or close margins was 100% vs. 56% in patients with positive margins (p = 0.002). Cox proportional hazards regression analysis was performed using the following variables as covariates: tumor dose, overall treatment time, interval from surgery to initiation of radiation therapy, margin status, grade, and tumor size. Total dose (p = 0.04) and margin status (p = 0.02) were found to significantly influence local control. Only tumor size significantly influenced distant metastasis (p = 0.01) or survival (p = 0.03).nnnCONCLUSIONnPostoperative radiation therapy doses > 62.5 Gy were noted to significantly improve local control in patients with extremity soft tissue sarcomas. This is the first analysis in the literature to demonstrate the independent influence of total dose on local control of extremity soft tissue sarcomas treated with adjuvant postoperative irradiation.

EFFECT OF HIGHER RADIATION DOSE ON BIOCHEMICAL CONTROL AFTER RADICAL PROSTATECTOMY FOR PT3N0 PROSTATE CANCER

PURPOSEnThe appropriate radiation dose has not been determined for postoperative radiation therapy (RT) of prostate cancer. Postoperative PSA level is a useful marker of local residual disease, and may allow evaluation of RT dose-response after radical prostatectomy.nnnMETHODS AND MATERIALSnBetween 1989 and 1996, 86 consecutive patients with pT3N0 prostate cancer who did not receive prior hormonal therapy or chemotherapy were irradiated postoperatively. All patients received 55.8 to 70.2 Gy (median = 64.8 Gy) to the prostatic/seminal vesicle bed. Patients were judged to be free of biochemical failure (bNED) if their PSA remained undetectable or decreased to undetectable level (< 0.2 ng/ml). The median follow-up time was 32 months from time of irradiation.nnnRESULTSnUnivariate and multivariate analyses of variables showed that the preRT PSA level was the most significant predictor of improved bNED survival (p < 0.001). Actuarial analyses of radiation dose grouped with preRT PSA levels found higher radiation dose to be significant (p < 0.05). For the 52 patients with an undetectable preRT PSA level, the 3-year bNED rate was 91% for patients irradiated to 61.5 Gy or more and 57% for those irradiated to lower doses (p = 0.01). For the 21 patients with preRT PSA level > 0.2 and < or = 2.0 ng/ml, the 3-year bNED rate was 79% for patients irradiated to 64.8 Gy or more and 33% for those irradiated to a lower dose (p = 0.02). No other preRT PSA interval or radiation dose level was associated with a dose-response function.nnnCONCLUSIONnIn patients with pT3N0 prostate cancer after radical prostatectomy, a radiation dose-response function may be present and depends on the preRT PSA value. Patients with high postoperative PSA levels (> 2.0 ng/ml) may be less likely to benefit from higher doses of RT, and should be considered a group for which systemic therapy should be tested.

White matter changes are correlated significantly with radiation dose. Observations from a randomized dose-escalation trial for malignant glioma (Radiation Therapy Oncology Group 83-02).

Background. A Phase I/II randomized dose‐seeking trial was performed to document the severity, time course, and significance of white matter changes seen on serial imaging scans (magnetic resonance imaging, computed tomography) associated with bis‐chlorethyl nitrosourea (BCNU) and hyperfractionated cranial irradiation.

Conformal treatment of prostate cancer with improved targeting: Superior prostate-specific antigen response compared to standard treatment

PURPOSEnConformal radiation therapy (CRT) decreases the morbidity of prostate cancer treatment, but no published data attest to the improved ability of CRT to control disease. Therefore, we compared Prostate-Specific Antigen (PSA) response at 1 year among similarly staged patients treated by conformal techniques to those treated with conventional approaches, looking for an early indicator of tumor response.nnnMETHOD AND MATERIALSnPatients with locally advanced disease were treated by pelvic field followed by prostate field conedowns; those with early stage/low grade disease received only prostate field irradiation. Between October, 1987 and November, 1991, conventional treatments used rectangular beams with or without corner blocks. Neither urethrography nor immobilization casts were used for conventionally treated patients. Between April, 1989 and December, 1992, conformal treatments have used rigid immobilization and Computed Tomography-based, beams-eye-view field design. As such, our conformal approach allowed improved targeting. Median prescribed doses (minimal doses to the Planning Target Volume) were 70 Gy (66-73 Gy) and 70.2 Gy (64.8-75 Gy) for conventionally and conformally treated patients, respectively. Median daily fraction size was 1.8 Gy for conventional treatment and 2.0 Gy for conformal therapy. Baseline PSA data were available on 170 consecutive patients treated conformally and 90 consecutive patients treated conventionally.nnnRESULTSnAmong those receiving only prostatic field irradiation, 12-month PSA values returned to normal in 96% and 85% of conformally and conventionally treated patients, respectively, when normalization was defined as < or = 4 ng/ml (p < 0.03) and in 76% vs. 55% of patients when PSA normalization was defined as < or = 1.5 ng/ml (p < 0.02). Among those receiving pelvic irradiation prior to prostatic conedown, PSA normalization (< or = 4 ng/ml) occurred in 82% and 61% (p < 0.01) of conformally and conventionally treated patients, respectively, and in 56% vs. 38% of patients when normalization was defined as < or = 1.5 ng/ml (p < 0.05). In a multivariate analysis, pretreatment PSA level (< or = 15 vs. > 15), and the use of conformal irradiation were statistically significant prognostic discriminants of PSA normalization at 1 year while total irradiation dose, clinical stage, and the addition of pelvic fields were not significant.nnnCONCLUSIONSnAs measured by PSA normalization, conformal techniques with improved targeting produced responses that were significantly better than conventional techniques among patients treated with definitive irradiation. These results, coupled with our previously documented reduction of acute and chronic sequelae, support the continued use of CRT as a more effective method of treatment for prostate cancer.