Merle M. Salter

CONVENTIONAL FOUR-FIELD PELVIC RADIOTHERAPY TECHNIQUE WITHOUT COMPUTED TOMOGRAPHY-TREATMENT PLANNING IN CANCER OF THE CERVIX: POTENTIAL GEOGRAPHIC MISS AND ITS IMPACT ON PELVIC CONTROL

PURPOSEnTo evaluate the impact of inadequate margins on pelvic control using the conventional four-field pelvic portals without computed tomography (CT)-treatment planning.nnnMETHODS AND MATERIALSnBetween 1986 and 1991, 34 patients with invasive cancer of the cervix were eligible for outcome study of conventional four-field radiation therapy (10 Stage I, 16 Stage II, 8 Stage III). The eligibility for this study includes four-field pelvic technique, definitive radiation therapy, and diagnostic CT scan of the pelvis. For this study, an inadequate margin is arbitrarily defined as < or = 1.0 cm of normal tissue around the CT-defined tumor volume.nnnRESULTSnAll 34 patients had adequate margins for anterio-posterior/posterio-anterior portals. However, 19 patients had an inadequate margin at the posterior border (S2-S3 interspace) and/or custom-shaped rectal block for lateral pelvic portals. Two patients had inadequate margins at the anterior border (level of symphysis pubis) due to an enlarged uterus. With a median follow-up of 36 months, pelvic control for adequate margins and inadequate margins was 100% and 71% for Stage IB disease and 88% and 50% for Stage IIB disease, respectively. However, pelvic control for Stage IIIB disease was 50% for both groups. There was no difference in total dose to point A or point B between the two groups.nnnCONCLUSIONnOur preliminary data show higher local failure in patients with an inadequate margin. For four-field pelvic radiation therapy, we strongly recommend CT-treatment planning. Otherwise, anterio-posterior/posterio-anterior pelvic therapy is the most reliable treatment for cancer of the uterine cervix.

Treatment of recurrent head and neck cancer with 5-fluorouracil, hydroxyurea, and reirradiation

Head and neck cancer locally recurrent after previous irradiation and surgery presents a difficult management problem. Conventional treatment alternatives include chemotherapy, reirradiation with interstitial implant, and hyperthermia. Reirradiation with external beam is generally not considered because of previous high radiation dose and limited tissue tolerance. In this study, 21 patients with recurrent and previously irradiated head and neck cancer were treated in a Phase I-II fashion. Patients received 5 days of 5-fluorouracil, 300 mg/m2/day IV bolus, Hydroxyurea 1.5 or 2 g/day by mouth and external beam radiation therapy every 2 weeks for up to four courses. Of 20 evaluable patients, 9 have attained a complete response (CR) and 6 a partial response (PR). Fifteen patients completed all planned therapy, eight on time, seven patients with delays. With a median follow-up of 7 months, 13 patients are alive, 7 disease-free (3 after salvage surgery) and 6 with recurrence. Eight patients have died. The 1-year survival is 56%. Treatment toxicity was mainly neutropenia. No major early or late radiation related side effects have been observed at a median follow-up of 7 months. Neither previous radiation dose, time since first radiation, prior chemotherapy, or site of recurrence was predictive of response or treatment tolerance. Patients with a performance status of at least 80 had a significant higher CR rate, with 7/10 patients in this group, as compared to 2/10 patients in patients with a performance status less than 80, achieving a CR. Reirradiation with 5-fluorouracil and hydroxyurea is a well tolerated outpatient treatment program for patients with recurrent and previous irradiated head and neck cancer that produces a high response rate and can provide significant palliation of symptoms.

Thoracic and Elective Brain Irradiation with Concomitant or Delayed Multiagent Chemotherapy in the Treatment of Localized Small Cell Carcinoma of the Lung: A Randomized Prospective Study by the Southeastern Cancer Study Group

A prospective randomized study was carried out to compare the effectiveness of concomitant or delayed multiagent chemotherapy combined with irradiation to the primary tumor and regional lymph nodes and to the brain in a group of 70 patients with histologically proven small cell undifferentiated carcinoma of the lung. Complete and partial response in both groups was comparable, and the overall survival was comparable. However, relapse‐free survival was significantly higher in patients receiving concomitant chemotherapy and irradiation in comparison with the radiotherapy alone group. Disease‐free survival was higher in the concomitant chemotherapy‐radiotherapy patients, although survival was not significantly modified, probably because of suboptimal chemotherapy. The initial intrathoracic failure rate was 40.7% in the concomitant chemotherapy‐irradiation group, compared with 53.8% in the radiotherapy‐alone patients. None of the patients receiving delayed chemotherapy following the radiotherapy recurrence showed signficant tumor response to the drugs. The incidence of distant metastasis was slightly lower in the chemotherapy groups. Brain metastases were noted in 7% of the patients in both groups. Increased intrathoracic recurrences were noted in patients with lower doses of irradiation. Nine of 13 patients treated with inadequate portals developed intrathoracic recurrences in comparison to 13 of 40 treated with adequate irradiation fields. The study emphasizes the need for intensive chemotherapy and adequate radiation therapy to improve survival of patients with small cell undifferentiated carcinoma of the lung. Additional trials are necessary to assess the role of each modality in the management of these patients.

Concomitant chemotherapy and reirradiation as management for recurrent cancer of the head and neck.

Thirty-five patients with inoperable recurrent head and neck cancer previously treated with definitive irradiation were treated with reirradiation and concomitant chemotherapy. Patient records were retrospectively reviewed to assess toxicity, response, and survival. Patients received one of three regimens: 1) 40 Gy total (2 Gy daily), 300 mg/m2 5-fluorouracil intravenous bolus, and 2 g hydroxyurea orally daily for 5 days; 2) 48 Gy total (1.2 Gy twice daily), 300 mg/m2 5-fluorouracil intravenous bolus, and 1.5 g hydroxyurea orally daily for 5 days; 3) 60 Gy total (1.5 Gy twice daily), 300 mg/m2 5-fluorouracil intravenous bolus, and 1.5 g hydroxyurea orally daily for 5 days. For all regimens, treatment was given only on weeks 1, 3, 5, and 7. Acute toxicity was mainly hematologic and was less severe with the lower hydroxyurea dose. Acute mucosal and skin toxicity was acceptable for all regimens. Late toxicity was noted in 4 of 17 patients who survived 12 months or more. Late effects were Radiation Therapy Oncology Group grade 3 or less. Fifteen of 35 patients achieved a complete response, and 11 of 35 patients achieved a partial response. The median survival rate was 10.5 months. There was no significant difference in responses or median survival between the groups. Reirradiation of head and neck cancer with 5-fluorouracil and hydroxyurea offers acceptable acute toxicity and minimal late effects. The clinical response rates and median survival are encouraging. Further investigation is warranted.

Conventional four-field pelvic radiotherapy technique without CT treatment planning in cancer of the cervix: potential geographic miss

The advantage of 4-field radiation to the pelvis is the use of lateral ports which spare the small bowel anteriorly and a portion of the rectum posteriorly from radiation. However, guidelines for the lateral pelvic ports are poorly defined. This is a comparative analysis to determine adequate margins by correlating conventional lateral pelvic treatment portals with CT defined tumor volume. The study included 52 patients treated definitively for carcinoma of the uterine cervix between 1986 and 1991. The most common site of inadequate margin (< or = 1.0 cm) was at the rectal block. The incidence of inadequate margin ranged from 39% to 50% and was independent of the stage of the disease except non-bulky stage IB disease. The next most common site was at the posterior border where frequency of inadequate margin for cervical tumor depended on stage with 8% of stage IB, 27% of stage IIB and 22% of stage IIIB/IVA disease. For the anterior border, an enlarged uterus was the only reason for inadequate margin rather than cervical tumor in 8% of stage IB, 18% of stage IIB, and 27% of stage IIIB/IVA disease. Without knowledge of precise tumor volume, the 4-field pelvic technique is potentially dangerous, risking underdosing of the tumor volume. For 4-field pelvic radiotherapy, we strongly recommend CT treatment planning.

Malignant epidural spinal cord compression associated with a paravertebral mass: its radiotherapeutic outcome on radiosensitivity.

PURPOSEnTo evaluate clinical characteristics and functional outcome of malignant epidural spinal cord compression associated with a paravertebral mass.nnnMETHODS AND MATERIALSnBetween 1987 and 1990, 136 patients with epidural spinal cord compression were treated with irradiation. Of these, 25 patients (18%) had epidural spinal cord compression associated with a paravertebral mass. This report is based on analysis of these 25 patients. Fourteen patients received 3000 cGy in 10 fractions. Seven received 4000 cGy in 16 fractions. Four received 2000 cGy in 5 fractions. Motor function was evaluated by five grades.nnnRESULTSnLung cancer accounted for the majority of epidural spinal cord compression with a paravertebral mass (60%) followed by lymphoma (8%) and kidney tumor (8%). This pattern of epidural spinal cord compression has a longer duration of pain before developing neurologic symptoms and has a high propensity of the upper thoracic spine involvement by an apical lung cancers. The functional outcome of radiation treatment reveals a significant difference between moderately radiosensitive tumors (lung, prostate, cervix, esophagus) and very radiosensitive tumor (lymphoma). None of the nonambulatory patients became ambulatory following radiotherapy except for the very radiosensitive tumors. Higher doses of radiation treatment (4000 cGy in 16 fractions) did not improve functional outcome.nnnCONCLUSIONnDue to the larger tumor burden, radiation treatment for epidural spinal cord compression associated with a paravertebral mass is not as effective as treatment of epidural spinal cord compression without a paravertebral mass except for the very radiosensitive tumor. Therefore, combined treatment modality might be beneficial for improving functional outcome.

Total lymphoid irradiation in the treatment of early or recurrent heart transplant rejection

PURPOSEnRecurrent acute cardiac allograft rejection is an important cause of repeat hospitalization and a major mode of mortality, particularly during the 6 months immediately following transplant. Total lymphoid irradiation (TLI) has been shown experimentally to induce a state of partial tolerance when administered prior to transplantation. Anecdotal reports of clinical experience have also suggested efficacy of TLI in treatment of recurrent cardiac rejection. The purpose of this study is to evaluate the safety and efficacy of TLI for treatment of early or recurrent heart transplant rejection.nnnMATERIALS AND METHODSnBetween January 1990 and June 1992, 49 patients postallograft cardiac transplant were given courses of TLI for treatment of early or recurrent rejection after conventional therapy with Methylprednisolone, antithymocyte globulin, OKT3, and methotrexate. Two patients failed to complete their therapy and were not evaluated. Two other patients received a second TLI course, making a total of 49 courses delivered. Indications for TLI were early rejection (n = 5), recurrent rejection (n = 38), and recurrent rejection with vasculitis (n = 6). The dose goal of the TLI protocol was 8 Gy in 10 fractions given twice weekly. Three separate fields were used to encompass all major lymph node-bearing areas. The actual mean dose was 7 Gy (range 2.4-8.4 Gy), and the duration of treatment was 8 to 106 days. These variations were secondary to leukopenia or thrombocytopenia.nnnRESULTSnThe mean posttransplant follow-up is 15 +/- 1.2 months (maximum 27 months). Among patients initiating TLI within 1 month posttransplant (n = 15), the rejection frequency decreased from 1.83 episodes/patient/month pre-TLI to 0.13 episodes/patient/month post-TLI (p < 0.001). For those who began TLI 1-3 months after transplant (n = 21), rejection decreased from 1.43 to 0.10 episodes/patient/month (p < 0.001). When TLI was started more than 3 months posttransplant (n = 11), the pre-TLI and post-TLI rejection frequencies were 0.67 and 0.07/patient/month (p < 0.001), respectively. The reduced post-TLI rejection frequencies were maintained to 24 months. There was no increase in the frequency of infection after TLI, nor were there any deaths during or immediately following TLI.nnnCONCLUSIONnTotal lymphoid irradiation is a safe and effective adjunct for prolonged control of early or recurrent cardiac rejection. Bone marrow suppression is transient in nearly all patients and is not associated with an increased incidence of infection. The long-term benefits, possible late deleterious effects, and the potential role of TLI as induction therapy remain to be elucidated.

A phase I study of high-dose cisplatin, prolonged infusion 5-fluorouracil, and concomitant conventional fraction radiation therapy in patients with inoperable squamous cell carcinoma of the head and neck.

Cisplatin (CDDP) and 5-fluorouracil (5-FU) have been used alone, in combination, and in various doses and sequences with radiation therapy in attempts to improve local control and survival of patients with advanced head and neck cancer. This study was undertaken to determine the toxicity and maximum tolerated dose of high-dose CDDP plus prolonged infusion 5-FU with concomitant conventional radiation therapy. Twenty-two patients with inoperable Stage III and IV squamous cell cancer were treated with CDDP (30 or 35 mg/m2 for 5 days every 4 weeks for three courses) and 5-FU (200 or 300 mg/m2 per day continuous i.v. infusion for 12 weeks) with concomitant conventional radiation therapy. This aggressive treatment regimen is accompanied by severe mucositis, myelosuppression, and chronic neuropathy. CDDP, 35 mg/m2/day χ 5, and 200 mg/m2/day of 5-FU infused over 12 weeks were identified as potential doses for future Phase II studies.

Phase I-II Study of Cisplatin, VP-16, MGBG, Mitomycin, and Vinblastine with Radiation Therapy for Non-Small-Cell Lung Cancer

Nineteen patients with locoregional non-small-cell lung cancer (NSCLC) were treated with two courses of cisplatin/VP-16/MGBG, followed by involved field radiotherapy and, subsequently, the same chemotherapy alternating with mitomycin-C/vinblastine. Five of 17 patients obtained a response (CR + PR) after induction chemotherapy. Following radiotherapy, an additional two patients responded. The median survival was 7.5 months, with the two longest survivors at 30 and 32 months. Hematologic toxicity was severe, with two deaths from severe neutropenia. Renal and gastrointestinal toxicities were moderate. This program of aggressive therapy did not increase the response rate or median survival compared with those of comparable patients treated in recent trials using radiotherapy alone or combined radiotherapy plus chemotherapy.

Local recurrence after breast conserving therapy for invasive breast cancer: analysis of prognostic factors

BackgroundIn recent years there has been a dramatic increase in the use of breast conservation therapy for patients with cancer. There are several factors associated with local recurrence but none are considered absolute contraindication for breast conserving therapy except multifocal carcinoma. This single-institution series investigates the effects of multiple factors on local relapse-free survival after breast-conserving therapy for women with invasive cancer.MethodsOne-hundred and ninety-two patients (193 cancers) with invasive carcinoma underwent breast-conserving therapy (surgery, radiation therapy and chemotherapy if indicated) at University of Alabama at Birmingham Hospital from 1986 through 1995. The Kaplan-Meier method was used to calculate curves for local recurrence. The log rank statistic test was used for statistical comparison between curves. The Cox proportional hazards model was used for multivariate analysis. Significance was defined as p<0.05.ResultsMean patient age was 56±12 years (range 25–83 years). Nineteen patients (9.8%) were 40 years age or younger. With a median time follow-up of 67 months the local recurrence rate for all patients was 6.7%. Ten patients developed local recurrence and three had combined local and distant recurrence. The mean local relapse-free interval was 71 months (range 10–148). The 5-year actuarial local relapse-free survival for all patients was 96%. Comparison of patients younger and older than 40 years age revealed a significantly lower risk of recurrence with increasing age (86 vs. 97% respectively, p=0.013). Patients 40 years age or younger with poorly differentiated tumors had a 5-year local relapse-free survival of only 40%. In multivariate analysis, only young age and poor tumor differentiation were found statistically significant in predicting local recurrence.ConclusionsAge and tumor differentiation are independent risk factors in our serie. These two factors should be taken into consideration when counseling breast cancer patients.ResumenAntecedentesEn años recientes ha habido un dramático incremento en la cirugía conservadora de mama para el tratamiento de pacientes con cáncer. Existen varios factores reportados que incrementan el riesgo de recurrencia local pero ninguno es considerado contraindicación absoluta para terapia conservadora, excepto el carcinoma multifocal. Esta serie de una sola institución investiga los efectos de múltiples factores sobre la sobrevida libre de recurrencia local después de tratamiento conservador para mujeres con carcinoma invasor de mama.MétodosCiento noventa y dos pacientes (193 cánceres) con carcinoma de mama invasivo fueron sometidas a tratamiento conservador (lumpectomía, radioterapia y quimioterapia si se encontraba indicada) en el Hospital de la Universidad de Alabama en Birmingham, USA de 1986 a 1995. Se utilizó el método de Kaplan-Meier para calcular las curvas de sobrevida y recurrencia local y la prueba de logrank para comparación estadística entre las curvas. Se utilizó el método de Cox para el análisis multivariado. Se definió significancia con una p<0.05.ResultadosLa edad promedio de las pacientes fue 56±12 años (rango 25–83 años). Diecinueve pacientes (9,8%) eran menores de 40 años de edad. Con una mediana de seguimiento de 67 meses, la tasa de recurrencia local para todas las pacientes fue 6.7%. Diez pacientes desarrollaron recurrencia local aislada y tres pacientes la combinación de recurrencia local y a distancia. El intervalo promedio libre de recurrencia local en estas pacientes fue de 71 bre de recurrencia local en estas pacientes fue de 71 meses (rango 10–148 meses). La sobrevida actuarial a 5 años libre de recurrencia local fue de 96% para todo el grupo de pacientes. La comparación de pacientes menores y mayores de 40 años demostró un riesgo significativamente menor de recurrencia local con mayor edad (86 frente al 97% respectivamente, p=0,013). Las pacientes menores de 40 años de edad con tumores poco diferenciados tuvieron una sobrevida actuarial libre de recurrencia local a 5 años de solo 40%. En el análisis mutivariado sólo la edad menor a 40 años y la pobre differenciación del tumor fueron encontrados predictores significativos de recurrencial local.ConclusionesLa edad y la diferenciación del tumor fueron encontrados predictores independientes. Estos factores deben ser tomados en consideración al plantear el tratamiento para las pacientes con carcinoma de mama invasivo.