Steve P. Lee

Quality of life after surgery, external beam irradiation, or brachytherapy for early-stage prostate cancer

The primary treatments for clinically localized prostate cancer confer equivalent cancer control for most patients but disparate side effects. In the current study, the authors sought to compare health‐related quality of life (HRQOL) outcomes after the most commonly used treatments.

Survivorship Beyond Convalescence: 48-Month Quality-of-Life Outcomes After Treatment for Localized Prostate Cancer

Decision making for treatment of localized prostate cancer is often guided by therapeutic side-effect profiles. We sought to assess health-related quality-of-life outcomes for patients 48 months after treatment for localized prostate cancer. Men treated for localized prostate cancer (N = 475) were evaluated before treatment and at 11 intervals during the 48 months after intervention. Changes in mean health-related quality-of-life scores and the probability of regaining baseline levels of health-related quality of life were compared between treatment groups. All statistical tests were two-sided. Urinary incontinence was more common after prostatectomy (n = 307) than after brachytherapy (n = 90) or external beam radiation therapy (n = 78) (both P < .001), whereas voiding and storage urinary symptoms were more prevalent after brachytherapy than after prostatectomy (both P < .001). Sexual dysfunction profoundly affected all three treatment groups, with a lower likelihood of regaining baseline function after prostatectomy than after external beam radiation therapy or brachytherapy (P < .001). Bowel dysfunction was more common after either form of radiation therapy than after prostatectomy. These results may guide decision making for treatment selection and clinical management of patients with health-related quality-of-life impairments after treatment for localized prostate cancer.

THE ROLE OF ADJUVANT RADIOTHERAPY IN THE TREATMENT OF RESECTABLE DESMOID TUMORS

PURPOSE Desmoid tumors have a high propensity for local recurrence with surgical resection. There are many reports describing good responses of desmoid tumors to irradiation, but none have clearly established the indications for adjuvant radiotherapy in treating resectable desmoid tumors. METHODS AND MATERIALS A retrospective analysis was performed on 61 patients with resectable desmoid tumor(s) who were treated at our institution from 1965 to February of 1992. Five patients had multifocal disease and are analyzed separately. Fifty-six patients had unifocal disease, of which 34 had positive surgical margins. Forty-five of the 56 patients with unifocal disease were treated with surgery alone, while 11 were treated with surgery plus adjuvant radiotherapy. Median follow-up was 6 years. Local control was measured from the last day of treatment, and all cases were reviewed by our Department of Pathology. RESULTS Multivariate analysis of the 56 patients with unifocal disease revealed that positive margins independently predicted for local recurrence (p < or = 0.01). Only 3 of 22 patients with clear margins experienced a local recurrence, with a 6-year actuarial local control of 85%. Multivariate analysis of the 34 patients with positive margins revealed that adjuvant radiotherapy independently predicted for improved local control (p = 0.01), and patients with recurrent disease had a slightly higher risk of local recurrence (p = 0.08). The 6-year actuarial local control determined by Kaplan-Meier for patients with unifocal disease and positive margins was 32% (+/-12%) with surgery alone, and 78% (+/-14%) with surgery plus adjuvant radiotherapy (p = 0.02). Subgroup analysis of the patients with positive margins and recurrent disease revealed that those treated with surgery alone had a 6-year actuarial local control of 0% vs. 80% for those treated with surgery plus radiotherapy (p < or = 0.01). Patients with positive margins and primary disease had a trend towards improved local control with adjuvant radiotherapy, but this was not statistically significant. None of the patients treated with radiotherapy developed serious complications or a secondary malignancy. CONCLUSIONS Margin status is the most important predictor of local recurrence for patients with resectable, unifocal desmoid tumor. Adjuvant radiotherapy is indicated in the treatment of patients with positive margins following wide excision of recurrent disease. The role of adjuvant radiotherapy in patients with positive margins following resection of primary disease is controversial, and should be based on a balanced discussion of the potential morbidity from radiotherapy compared to the potential morbidity of another local recurrence. Adjuvant radiotherapy is less likely to benefit those with clear margins due to the excellent results for these patients treated with surgery alone. The local control of desmoid tumor in the adjuvant setting is excellent with total doses ranging from 50-60 Gy, with acceptable morbidity. Field sizes should be generous to prevent marginal recurrences, and large volume MRIs of patients with extremity lesions should be used to identify those patients with multifocal disease.

Mucosal melanoma of the head and neck: The impact of local control on survival

The management for mucosal melanoma of the head and neck is controversial in view of the poor prognosis. Thirty‐five patients seen from 1955 to 1991 were analyzed retrospectively. Almost all (34/35) presented with localized disease. Primary treatments included radical surgery (15), local resection (11), radiation therapy (6), or systemic treatment (2). While the rate of local recurrence was high (27/34), only 5 patients developed distant disease before local relapse. Furthermore, only 5/21 achieved successful local salvage. Patients with their disease controlled locally had significantly longer survival than those with persistent local disease (P = .0001). The 5‐year disease‐specific survival was 45%.

The prognostic significance of pre- and posttreatment SCC levels in patients with squamous cell carcinoma of the cervix treated by radiotherapy

PURPOSE To investigate the prognostic significance of the pre- and posttreatment serum squamous cell carcinoma antigen (SCC) levels in patients with Stage I-IVA squamous cell carcinoma of the cervix primarily treated by radiotherapy. MATERIALS AND METHODS 401 patients with squamous cell carcinoma of cervix primarily treated with radiotherapy (RT) were included in this study. All had preRT, and 249 patients had postRT serum SCC values. The association of pretreatment SCC level with the clinical parameters, including stage, hemoglobin (Hb) level, age, cell differentiation, and lymph node status, was assessed by univariate and multivariate analysis. The prognostic significance of pretreatment SCC level and these clinical parameters were evaluated. The impact of postRT residual induration and SCC levels on survival was analyzed. RESULTS 1. PreRT SCC level strongly correlated with stage. After controlling for stage, only SCC levels higher than 10 ng/ml were associated with enlarged lymph nodes shown in CT scan. No association of preRT SCC level with other clinical parameters was found. 2. SCC level higher than 10 ng/ml, but not between 2-10 ng/ml, had significant impact on survival in a multivariate analysis. Stage, Hb levels (<10 g/dl) and positive lymph node shown by CT scan were also independent prognostic factors for survival. No significant difference in failure pattern in terms of local and/or distant sites was found in patients with different SCC levels. 3. Patients with residual induration and/or persistently elevated SCC level at 2-3 months after RT had a significantly higher incidence of treatment failure. Persistently elevated SCC level is a stronger predictor for treatment failure than residual induration by pelvic examination, and is associated with a higher incidence of distant metastasis. One third of patients with initial SCC level higher than 10 ng/ml had persistently elevated SCC. CONCLUSION Pretreatment SCC levels higher than 10 ng/ml are an independent predictor for poor prognosis in patients included in this study, and can be used as one of the prognostic factors for selection of patients for intensive treatment. Persistently elevated SCC levels after RT is a strong predictor for treatment failure. A combination of clinical pelvic examination and SCC levels provides useful information for the need of further work-up and management.

The role of brachytherapy in early-stage nasopharyngeal carcinoma

PURPOSE To present the treatment results and assess the optimal radiation dose and the role of brachytherapy in early stage nasopharyngeal cancer (NPC). METHODS AND MATERIALS One hundred eighty-three patients with Stage I and II (American Joint Committee on Cancer Staging System, 1987) NPC completed the planned radiotherapy in our institution from 1979 to 1991. In 133 patients, radiotherapy was given to the nasopharynx by external beam to 64.8-68.4 Gy. Further boost was done by high dose rate (HDR) brachytherapy for 5-16.5 Gy in one to three fractions. For the remaining 50 patients, a course of external radiotherapy to the nasopharynx for 68.4-72 Gy was given to nasopharynx. Age (>40 or not), sex, neck boost or not, brachytherapy, and irradiation dose were analyzed to determine significant factors that influence the probabilities of local control and actuarial survival. RESULTS The 5-year disease-specific survival was 85.8% and local control was 83%. Only the brachytherapy and irradiation dose significantly affected the results. The use of the brachytherapy had significant impact on overall survival and local control. Furthermore, we compared the prognostic effect of various radiation dosage among Group I of 50 patients (<72.5 Gy, no brachytherapy, excluding four patients who received brachytherapy), Group II of 71 patients (72.5-75 Gy; one to two fractions of brachytherapy), and Group III of 58 patients (>75 Gy; three fractions of brachytherapy). Five-year disease-specific survival rates of Group I, Group II, and Group III were 77, 95.5, and 82.4%, respectively. Five-year local control rates were: 73.7, 93.9, and 79.5%. We found that the Group II had the best actuarial survival and local control rate (log-rank test,p < 0.05). Most patients receiving brachytherapy encountered foul odor because of nasopharynx crust; 12 of them had palate or sphenoid sinus floor perforation or nasopharynx necrosis. None of the patients without brachytherapy experienced the same complications. CONCLUSIONS The optimal radiotherapy dose to the nasopharynx area in early stage NPC may be within 72.5 to 75 Gy by our treatment protocol. A dose of more than 75 Gy did not have significant local control or survival advantage. The use of brachytherapy to elevate radiation dose had significant local control and survival benefit for early stage NPC patients, but the fractionation size should be decreased to reduce the complications.

Nasopharyngeal carcinoma: Treatment results with primary radiation therapy

One hundred three patients with nasopharyngeal carcinoma were treated with radiotherapy at UCLA Medical Center from January 1955 to December 1990. Overall survival, disease‐free survival, and local control rates were analyzed. In addition, survival from 1955 to 1978 and from 1979 to 1990 were evaluated. Overall 5‐ and 10‐year actuarial survival rates for all patients were 58% and 47%, respectively. Disease‐free survival rates at 3 and 5 years were 45% and 30%, respectively. Local, persistent, or recurrent disease in the nasopharynx was the primary cause of failure, occurring in 32% of patients and correlating with the initial tumor size (T stage). Twenty‐four percent of patients developed distant metastases, which correlated with nodal status but not with T stage. Seventy‐nine percent of patients failed either locally or distally by 4 years. Sex, race, age, and T and N stage categories were evaluated as prognostic variables in terms of survival. Control of primary disease is important in determining long‐term outcome. Modern imaging techniques have greatly assisted in the evaluation of disease extent and treatment options.

Second malignant tumors in patients with nasopharyngeal carcinoma and their association with Epstein-Barr virus.

Since previous published studies about second malignant tumors (SMTs) in nasopharyngeal carcinoma (NPC) patients usually included a limited sample size and did not attain consistent results, we conducted a large retrospective study in a cohort of 1,549 patients to assess the risk of SMT in NPC patients following radiotherapy (RT) in Taiwan. The follow‐up period ranged from 2 to 16 years, with a median of 7 years. Thirty‐nine patients developed SMTs during the 7,145 person‐year follow‐up [standardized incidence ratio (SIR): 2.8; 95% confidence interval (CI): 2.0 to 3.9]. Increased risks of developing SMTs were observed for head and neck (H/N) cancer (SIR: 16.5; 95% CI: 10.0 to 26.8), gastric cancer (SIR: 5.5; 95% CI: 2.2 to 11.4) and leukemia (SIR: 9; 95% CI: 1.9 to 26.3). Paraffin‐embedded specimens of secondary H/N cancer (11), secondary gastric cancer (6) and their corresponding NPC specimens were examined by EBER in situ hybridization to assess the association between Epstein‐Barr virus (EBV) and these SMTs. Twenty‐six primary H/N and 5 gastric cancer specimens were chosen as the control groups. In H/N cancer, EBV was detected in 3.8% of the primary cancers and 9.1% of the secondary cancers. All the positive specimens resulted from hypopharyngeal cancer. Of the secondary gastric cancers, only 1 case (16.6%) was associated with EBV. None of the primary gastric cancers was associated with EBV. Our results indicate an increased risk of developing SMTs, with a preference for head and neck cancer, gastric cancer and leukemia, in NPC patients after RT in Taiwan. Only a small proportion of the secondary H/N and gastric cancers was associated with EBV. Int. J. Cancer 87:228–231, 2000.

Long-Term Outcome and Prognostic Factors for Adenocarcinoma/Adenosquamous Carcinoma of Cervix After Definitive Radiotherapy

PURPOSE To study the outcomes of patients with adenocarcinoma/adenosquamous carcinoma (AC/ASC) of the cervix primarily treated with radiotherapy (RT), identify the prognostic factors, and evaluate the efficacy of concurrent chemoradiotherapy (CCRT) or salvage surgery. METHODS AND MATERIALS A total of 148 patients with Stage I-IVA AC/ASC of cervix after full-course definitive RT were included. Of the 148 patients, 77% had advanced stage disease. Treatment failure was categorized as either distant or local failure. Local failure was further separated into persistent tumor or local relapse after complete remission. The effectiveness of CCRT with cisplatin and/or paclitaxel was examined, and the surgical salvage rate for local failure was reviewed. RESULTS The 5-year relapse-free survival rate was 68%, 38%, 49%, 30%, and 0% for those with Stage IB/IIA nonbulky, IB/IIA bulky, IIB, III, and IVA disease, respectively, and appeared inferior to that of those with squamous cell carcinoma of the cervix treated using the same RT protocol. Incomplete tumor regression after RT, a low hemoglobin level, and positive lymph node metastasis were independent poor prognostic factors for relapse-free survival. CCRT with weekly cisplatinum did not improve the outcome for our AC/ASC patients. Salvage surgery rescued 30% of patients with persistent disease. CONCLUSION Patients with AC/ASC of the cervix primarily treated with RT had inferior outcomes compared to those with squamous cell carcinoma. Incomplete tumor regression after RT was the most important prognostic factor for local failure. Salvage surgery for patients with persistent tumor should be encouraged for selected patients. Our results did not demonstrate a benefit of CCRT with cisplatin for this disease.

A Prospective Randomized Trial to Study the Impact of Pretreatment FDG-PET for Cervical Cancer Patients With MRI-Detected Positive Pelvic but Negative Para-Aortic Lymphadenopathy

PURPOSE This prospective randomized study was undertaken to determine the possible impact of 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) on extrapelvic metastasis detection, radiation field design, and survival outcome for cervical cancer patients with enlarged pelvic nodes on MRI image. METHODS AND MATERIALS Inclusion criteria were patients with newly diagnosed Stage I-IVA cervical cancer and with positive pelvic but negative para-aortic lymph nodes (PALN) as detected by magnetic resonance image and good performance status for concurrent chemoradiotherapy. Eligible patients were randomized to receive either pretreatment FDG-PET (study group) or not (control group). Whole pelvis was the standard irradiation field for the control group and those with no extrapelvic findings on PET. The radiation fields for the rest of the study group were extended to include the PALN region or were modified according to the extrapelvic PET finding. RESULTS From January 2002 to April 2006, 129 patients were included, and 66 of them were randomized to receive FDG-PET. PET detected seven extrapelvic metastases (11%, 6 PALN and 1 omental node), and four of them remained disease-free after treatment modification. For patients who underwent PET compared with those who did not, there were no differences in the 4-year rates of overall survival (79% vs. 85%, p = 0.65), disease-free survival (75 % vs. 77%, p = 0.64), and distant metastasis-free survival (82% vs. 78%, p = 0.83). CONCLUSIONS Pretreatment FDG-PET in conjunction with magnetic resonance imaging can improve the detection of extrapelvic metastasis, mainly PALN, and help select patients for extended-field radiotherapy. However, the addition of FDG-PET may not translate into survival benefit, even though PALN relapses are reduced.