Adenocarcinoma of the uterine cervix. Prognosis and patterns of failure in 367 cases

Between 1965 and 1985, 367 patients received initial treatment for adenocarcinoma of the uterine cervix at the M. D. Anderson Cancer Center (MDACC). Of the 334 patients treated with curative intent, 223 had International Federation of Gynecology and Obstetrics (FIGO) Stage I, 60 had Stage II, and 51 had Stage III/IV disease. The 5-year and 10-year relapse-free survival (RFS) rates for all patients treated for Stage I disease were 73% and 70%, respectively. RFS was strongly correlated with initial bulk of disease (P = 0.002), although locoregional control (LRC) was good in all groups: 91 patients with a normal-sized cervix (tumor less than 3 cm) had a 5-year RFS rate of 88% and an actuarial LRC rate of 94%; 102 patients with lesions 3 to 5.9 cm in diameter had an RFS rate of 64% and an LRC rate of 82%; and 22 patients with bulky lesions greater than 6 cm in diameter had a comparable LRC rate of 81%, but an RFS rate of only 45%. Decreased RFS also was strongly correlated with positive lymphangiogram (LAG) results (P = 0.02) and poorly differentiated lesions (P = 0.0014). When initial primary tumor size was taken into account, there was no significant difference in RFS or LRC between patients treated with radiation (RT) alone or RT plus extrafascial hysterectomy (R + S). The 5-year and 10-year RFS rates of 60 patients who received curative therapy for Stage II disease were 32% and 25%, respectively, with an LRC rate of 62% at 5 years. Patients with bulky Stage II disease did particularly poorly, with a 5-year RFS rate of 15%. Decreased RFS was correlated with positive LAG results and poorly differentiated tumors. Most Stage II patients whose disease relapsed died with distant metastases (73%). Forty-eight patients with Stage III/IV disease treated with curative intent had a 5-year survival rate of 31% and a 5-year pelvic disease control rate of 52%. In summary, patients with small volume Stage IB lesions have excellent LRC and survival with RT alone. RT achieves good LRC of bulkier Stage I lesions, but survival decreases with increasing primary tumor size. R + S holds no apparent advantage over RT alone. Patients with more advanced disease have a high rate of relapse with frequent distant metastasis. In particular, the survival of patients with FIGO Stage II disease is much lower than what we have observed after treatment of comparable stage squamous carcinoma.(ABSTRACT TRUNCATED AT 400 WORDS)     

Long-term survival of nasopharyngeal carcinoma patients treated with adjuvant chemotherapy subsequent to conventional radical radiotherapy

PURPOSE: To assess the long-term survival of patients with nasopharyngeal carcinoma (NPC) who were treated with conventional radical radiotherapy (RT) followed by adjuvant chemotherapy. METHODS AND MATERIALS: Ninety-one newly diagnosed patients with Stage III and IV (American Joint Committee on Cancer, 1988) NPC, seen at the University of Malaya Medical Center, Kuala Lumpur, Malaysia between January 1992 and May 1997, were treated with RT followed by adjuvant chemotherapy. The tumor dose was 70 Gy delivered in 35 fractions, 5 fractions weekly. Three cycles of chemotherapy, each consisting of 5-fluorouracil, 1 g/m(2)/d on Days 1-4 and cisplatin 100 mg/m(2) on Day 1, were administered 3 weeks after RT completion. Thirty-six patients had Stage II, 10 had Stage III, and 45 had Stage IV disease (AJCC 1997 staging system). RESULTS: After a median follow-up of 61 months, the 5-year overall survival rate for all 91 patients was 80.1%, the disease-free survival rate was 76%, and the locoregional control rate was 85%. The 3-year overall survival rate for Stage II was 94.3%; it was 80% for Stage III and 79.8% for Stage IV (p = 0.0108). The 3-year DFS rate for Stage II was 90%; it was 80% for Stage II and 65% for Stage IV. The rate of distant failure for Stage IV was 8.9%. CONCLUSION: Radical RT followed by adjuvant chemotherapy was effective in our patients with locoregionally advanced NPC. The long-term results appear encouraging, even for patients with Stage IV disease. This single institution experience deserves further investigation in prospective trials.     

Impact of T and N stage and treatment on survival and relapse in adjuvant rectal cancer: a pooled analysis.

PURPOSE: To determine survival and relapse rates by T and N stage and treatment method in five randomized phase III North American rectal adjuvant studies. PATIENTS AND METHODS: Data were pooled from 3,791 eligible patients enrolled onto North Central Cancer Treatment Group (NCCTG) 79-47-51, NCCTG 86-47-51, US Gastrointestinal Intergroup 0114, National Surgical Adjuvant Breast and Bowel Project (NSABP) R01, and NSABP R02. Surgery alone (S) was the treatment arm in 179 patients. The remaining patients received adjuvant treatment as follows: irradiation (RT) alone (n = 281), RT + fluorouracil (FU) +/- semustine bolus chemotherapy (CT; n = 779), RT + protracted venous infusion CT (n = 325), RT + FU +/- leucovorin or levamisole bolus CT (n = 1,695), or CT alone (n = 532). Five-year follow-up was available in 94% of surviving patients, and 8-year follow-up, in 62%. RESULTS: Overall (OS) and disease-free survival were dependent on TN stage, NT stage, and treatment method. Even among N2 patients, T substage influenced 5-year OS (T1-2, 67%; T3, 44%; T4, 37%; P <.001). Three risk groups of patients were defined: (1) intermediate (T1-2/N1, T3/N0), (2) moderately high (T1-2/N2, T3/N1, T4/N0), and (3) high (T3/N2, T4/N1, T4/N2). For intermediate-risk patients, those receiving S plus CT had 5-year OS rates of 85% (T1-2/N1) and 84% (T3/N0), which was similar to results with S plus RT plus CT (T1-2/N1, 78% to 83%; T3/N0, 74% to 80%). For moderately high-risk lesions, 5-year OS ranged from 43% to 70% with S plus CT, and 44% to 80% with S plus RT plus CT. For high-risk lesions, 5-year OS ranged from 25% to 45% with S plus CT, and 29% to 57% with S plus RT plus CT. CONCLUSION: Different treatment strategies may be indicated for intermediate-risk versus moderately high- or high-risk patients based on differential survival rates and rates of relapse. Use of trimodality treatment for all patients with intermediate-risk lesions may be excessive, since S plus CT resulted in 5-year OS of approximately 85%; however, 5-year disease-free survival rates with S plus CT were 78% (T1-2/N1) and 69%(T3/N0), indicating room for improvement.     

Radiation therapy for squamous cell carcinoma of the supraglottic larynx

Sixty-five patients with invasive squamous cell carcinoma of the supraglottic larynx received irradiation with curative intent between 1975 and 1984, with a 5-year actuarial survival of 48% and a local control rate of 70%. Five-year survivals for clinical Stages I, II, and III + IV were 60, 53, and 52%, respectively; local control rates were 88, 76, and 63%, respectively. These patients included one treated with preoperative irradiation, 35 treated with surgery followed by postoperative irradiation, and 29 treated with radiation therapy alone. In the surgery plus irradiation group, 5-year local control was 93% for clinical Stages I + II (14 patients), and 61% for clinical Stages III + IV (21 patients). Three patients had pathologic Stage II disease, with the remainder demonstrating a higher pathologic than clinical stage. Multiple positive nodes predisposed to local/regional recurrence, while no relationship could be established between recurrence and extracapsular nodal spread, positive margins, emergency tracheostomy, total versus less-than-total laryngectomy, radiation field size, radiation dose, or delay until radiation therapy, probably because of patient numbers. Six patients, five with positive nodes, developed distant metastases, and three developed second primary tumors outside the head and neck region. In the radiation therapy alone group, 5-year local control rates were 86, 59, and 53% for clinical Stages I (7 patients), II (11 patients), and III + IV (11 patients), respectively. However, three of four Stage II local/regional failures were surgically salvaged for periods greater than 30 months, for an ultimate Stage II local control of 89%. No relationship could be established between local control and radiation dose or field size, again probably because of small patient numbers. Three patients developed distant metastases, and eight developed second malignancies, one within the irradiated volume. Fifteen patients developed acute toxicity during irradiation, and there were eight chronic complications, five requiring surgery; toxicity was more common in the group treated with radiation alone. Radiation therapy alone with surgical salvage is an effective, function-preserving treatment for clinical Stages I and II carcinoma of the supraglottic larynx, and appears to yield local control and survival comparable with that of combined irradiation and surgery in more advanced disease.     

Radiation therapy alone for medically inoperable patients with adenocarcinoma of the endometrium

Surgery with adjuvant radiation is the definitive method for treating patients with Stage I and II FIGO endometrial carcinoma. However, radiation therapy alone becomes the only curative alternative for patients who presented with severe, acute, and chronic medical illnesses which prevented surgical management. We report on 104 such patients treated at Centre Alexis Vautrin in Nancy (FRANCE) between 1975 and 1984. The minimum follow-up was 2 years, the maximum was 11 years. Fifty-two patients were treated by association of external irradiation (RT) and curietherapy (CUR), and 52 by curietherapy alone. The median age of the patients was 68.8 years with a minimum of 43 and maximum of 89 years old. Ninety-six patients (92.3%) were obese. Forty-nine (47.1%) were hypertensive. Forty-one (39.4%) had cardiovascular diseases, 25 (24%) had diabetes mellitus, and 13 (12.5%) had history of phlebitis. Seventy-nine patients (75.9%) were Stage I FIGO, 15 (14.4%) were Stage II, 4 patients (3.8%) were Stage III, and 6 patients (5.7%) were Stage IV. The 5- and 10-year overall absolute survival was 51.6% and 35.9% respectively. The 5- and 10-year determinate survival was 65.9% and 58.6% respectively. The 5- and 10-year absolute survival of patients treated by combination RT + CUR was 59.6 and 49.8% respectively. The 5- and 10-year survival of patients treated by CUR alone was 42.3% and 27% significantly worse (p = 0.025). The 5- and 10-year determinate survival for Stage Ia was 82.1%, 71.4% and for Stage Ib 64.6% and 64.6% respectively. The difference was not significant (p = 0.18). While the 5- and 10-year determinate survival for Stage II was 56.2% and 56.3%, significantly worse than Stage I patients (p = 0.043). Tumor differentiation (G) was found to be a significant prognostic factor in survival (p less than 0.05). Local failure was seen in 9 patients (8.6%) 5 in association with distant metastasis (DM). The 5- and 10-year actuarial local control were 87.6% and 85.1% respectively. Severe complications occurred in 18 patients (17.3%). Five of these patients are still alive with a mean follow-up of 8.8 years (minimum 6 years and maximum 11 years). The rate of complications had considerably diminished after 1980, as techniques improved and computerized dosimetry was used.     

Comparison of the Radiation Therapy Oncology Group and American Joint Committee on Cancer staging systems among patients with non-small cell lung cancer receiving hyperfractionated radiation therapy. A report of the Radiation Therapy Oncology Group protocol 83-11.

Since 1973, the Radiation Therapy Oncology Group (RTOG) has staged and stratified patients in non-small cell lung cancer (NSCLC) protocols according to the RTOG staging system. In 1985, the American Joint Committee on Cancer (AJCC) revised its lung cancer staging system, with the principle differences from the RTOG system being the staging of involvement of the chest wall and of contralateral mediastinal and hilar lymph nodes. To determine if the AJCC system discriminated outcome differently than the RTOG system in a nonoperative series, all 850 evaluable patients treated with hyperfractionated radiation therapy (RT) on the RTOG protocol 83-11 were restaged by the AJCC system. There was 67% agreement in patient distribution between the following comparable stages in each system: RTOG Stage II/AJCC Stage II; RTOG Stage III/AJCC Stage IIIA; and RTOG Stage IV/AJCC Stage IIIB. Both systems successfully predicted for survival (P less than 0.001), although the RTOG staging was more discriminating (relative risk ratios, 1.59 versus 1.38). Among the 507 favorable patients (those with less than or equal to 5% weight loss and Karnofsky performance status [KPS] of 70 to 100), the RTOG staging was also more predictive (P = 0.004 versus P = 0.01). When RTOG Stage III (462 patients) was divided into those without contralateral mediastinal or hilar adenopathy (AJCC Stage II/IIIA) and those with (AJCC Stage IIIB), a significant survival (P = 0.0001) was noted with 2-year survival rates of 26% versus 4%, respectively. When AJCC Stage IIIA (348 patients) was divided into the patients without chest wall invasion (RTOG Stage II/III) and those with (RTOG Stage IV), a difference in 2-year survival of 22% versus 10% was observed (P = 0.002). Although both staging systems independently predict for survival, a fusion of both staging systems is the most discriminating of outcome. Future nonoperative studies in locally advanced NSCLC should stratify for contralateral nodal involvement (per AJCC staging) and chest wall invasion (per RTOG staging).     

Outcomes of patients receiving radiation for carcinoma of the rectum. Results of the 1988-1989 patterns of care study

BACKGROUND: Clinical trials of surgical adjuvant treatment for patients with rectal carcinoma (RC) indicate that postoperative radiation therapy with concurrent chemotherapy (CRT) is superior to postoperative radiation alone (RT) or surgery alone. Whether preoperative treatment is superior to postoperative treatment is controversial. This Patterns of Care Study (PCS) surveyed patients with RC treated with radiation during the years 1988-1989 to determine the national practice standards and outcomes and to compare these results with those of clinical trials. METHODS: A national survey of 73 institutions was conducted using 2-stage cluster sampling, and specific information on 406 patients with RC who received radiation at 69 facilities was collected. Follow-up information on 215 patients was subsequently collected by mail survey. There were no significant differences between the known prognostic indicators or treatment-related variables for patients for whom follow-up was available compared with the variables for patients for whom follow-up was not available. Follow-up ranged from 0 to 8.44 years with a median of 4 years. One hundred fifty-four patients (71%) received postoperative treatment, either RT (37%) or CRT (34%); and 40 (18%) received preoperative treatment, either RT (15%) or CRT (3%). Ninety-six patients (45%) received chemotherapy, and for 86% of those patients chemotherapy was administered concurrently with radiation. RESULTS: Survival was stage-dependent (85% Stage I, 69% Stage II, and 54% Stage III at 5 years, P = 0.04). Survival was also substage-dependent, and patients with C(1) cancer had significantly higher 5-year survival than those with C(2)/C(3) cancer (89% vs. 48%, P = 0.008). Local failure was similar for Stage II and Stage III patients (10% vs. 11% at 5 years, respectively). In multivariate analyses, only stage and use of chemotherapy were significant to survival (Stage III vs. Stage I and II, relative risk [RR] = 2.52, and chemotherapy vs. no chemotherapy, RR = 0.46). A significantly higher 5-year survival rate was seen with postoperative CRT than with postoperative RT (69% vs. 50%, P = 0. 011). Preoperative radiation resulted in a significantly higher 5-year survival rate than postoperative radiation (85% vs. 50%, P = 0.0006), but not compared with postoperative CRT. Survival and local failure did not differ according to radiation therapy interruption or the interval between surgery and radiation. CONCLUSIONS: Stage is an important prognostic indicator for survival, and among patients with Stage III malignancies survival in the substage C(1) is significantly higher than in the substages C(2) and C(3). As has been demonstrated in randomized trials, adjuvant postoperative CRT is superior to postoperative RT for patients with RC in this national study. These nationwide results of adjuvant treatment are comparable to those reported in randomized trials. The use of CRT was the only treatment-related factor that resulted in a significant reduction in the risk of death.     

Larynx preservation using induction chemotherapy plus radiation therapy as an alternative to laryngectomy in advanced head and neck cancer. A long-term follow-up report.

Since 1977, we have used induction chemotherapy (CT) plus radiation therapy (RT) with curative intent in 35 advanced head and neck cancer (Ca) patients who otherwise would have required total laryngectomy. Fourteen patients had advanced Ca of the larynx or supraglottic larynx (SGL); 21 patients had Ca of the hypopharynx. In six patients the Ca was Stage III; in 26 patients it was Stage IV. Three patients had Stage II disease--2 with cancer of the pyriform sinus and one patient with Stage II SGL Ca who refused surgery. Chemotherapy consisted of platinum (P) + bleomycin in 18 patients until 1982, then P + fluorouracil in the next 17 patients. Total response rate was 77%--complete (CR) in 26% and partial (PR) in 51%. There were two toxic deaths. Surgery was limited to tracheostomy in 4 patients prior to CT and to radical neck dissection after CT in 4 others. Two patients required salvage laryngectomy at 11 and 31 months, respectively. One patient underwent partial laryngectomy with voice preservation. Thirty-two patients were evaluable for overall response after RT. Final disease-free status was achieved in 20/34. One long-term survivor was lost to follow-up (44 months) and 8 patients remained alive at 13+ to 109+ months. Median failure-free survival for all patients was no less than 24 months. Not counting 4 early deaths free of disease, 2-year local control using only chemotherapy plus radiation was 52% (16:31). Overall, 33 of 35 patients retained their voices. Sixteen patients (46%) have survived 2 years or longer. Survival of patients who achieved CR after induction chemotherapy was 48 months versus 14 months for those with less than a CR (p = 0.001). Patients with a hypopharyngeal primary had only a 33% 2-year local control rate with chemotherapy and radiation and a median survival of only 12 months versus 77% control and a minimum 39-month survival for those whose tumor arose in the larynx (p = 0.009). Induction chemotherapy plus radiation therapy is an effective strategy which can produce a high rate of larynx preservation, local control, and long-term survival in patients with advanced cancer of the larynx. Patients with hypopharyngeal primaries have a lesser rate of long-term survival and local control, despite similar overall response rates.     

Vaginal recurrences of endometrial carcinoma: the prognostic value of staging by a primary vaginal carcinoma system

Fifty-five of 1716 women with endometrial carcinoma seen consecutively at three institutions prior to 1986 were found to have an isolated post-hysterectomy vaginal recurrence. Their therapy included external radiation therapy (RT) and brachytherapy for 26 women, external RT alone for 17, brachytherapy only for 4, and no RT for 8. Combined external RT/brachytherapy doses ranged from 2000 to 10,000 cGy with a median of 6000 cGy. The 3- and 5-year actuarial survival rates are 48% and 31% for the entire group, and the 3- and 5-year pelvic control rates are 52% and 42%. The 5-year survival and pelvic control rates for those who received greater than or equal to 6000 cGy in total RT dose are 47% and 68%, compared with 12% and 10% for those receiving less than 6000 cGy (p = 0.002 and p = 0.004). For patients receiving their second RT course, the 5-year survival rate is 16%, compared with 48% for those not previously irradiated. The Perez modification of the International Federation of Gynecology and Obstetrics (FIGO) staging system for primary vaginal carcinoma was applied to each recurrence. There were 15 Stage I cases (vaginal mucosa), 32 Stage II cases divided between 15 Stage IIA (subvaginal infiltration) and 17 in Stage IIB (parametrial infiltration), and 8 Stage III cases (pelvic wall involvement). The 3-year actuarial survival and pelvic control rates using this staging system are: Stage I: 85%/100%; Stage II: 41%/43%, Stage IIA: 59%/53%, Stage IIB: 26%/35%; Stage III: 13%/0%. These outcome endpoints are significantly better for Stage I than Stage II patients (p = 0.01 & 0.0004) and for Stages I and IIA compared to Stages IIB and III (p = 0.0005 & 0.002). The pre-treatment variables of age, interval since hysterectomy, initial stage, and location did not predict for survival, but a higher rate of pelvic control was observed for apical than for suburethral recurrences (56% vs. 20%). Grade III histology was highly correlated with poor survival (p = 0.0006). This vaginal carcinoma staging system appears to have value in predicting treatment outcome for patients with post-hysterectomy vaginal recurrences.     

Long-term results of three-dimensional conformal radiation therapy for patients with rhabdomyosarcoma

BACKGROUND: The authors evaluated the outcome of patients with rhabdomyosarcoma (RMS) who were treated with three-dimensional (3D) conformal radiation therapy (RT) at a single institution. METHODS: The records of all 69 patients with RMS who received 3D RT from 1989 to 2001 were reviewed. All patients received multiagent chemotherapy with or without surgical resection. Follow-up of surviving patients ranged from 1.0 year to 12.8 years (median, 4.3 years). RESULTS: The median patient age was 6 years (range, 1-29 years), and there was a male:female ratio of 1.5:1. Forty-eight patients had embryonal sarcomas, 14 patients had alveolar sarcomas, and 7 patients had undifferentiated sarcomas. The parameningeal area (n = 22 patients) and the trunk (n = 21 patients) were the most common sites. Twelve percent of patients had Stage I disease, 10% of patients had Stage II disease, 51% of patients had Stage III disease, and 27% of patients had Stage V disease. Nine percent of patients were in clinical Group II, 64% of patients were in Group III, and 27% of patients were in Group IV. Regional lymph nodes were involved in 33% of patients, and 77% of tumors measured > or = 5 cm in greatest dimension. The actuarial 5-year local and regional control rates were 90% and 91%, respectively. No predictive factors for local failure were identified; however, alveolar histology was correlated with regional recurrence (29% compared with 4%; P = 0.02). The disease free and overall survival rates were 60% and 63% at 5 years, respectively. Disease stage was most predictive of 5-year survival (76% of patients with Stage I-III disease compared with 24% of patients with Stage IV disease; P < 0.001). CONCLUSIONS: High rates of local control were achieved in patients with RMS using 3D RT. Regional lymph node failure was increased significantly among patients with alveolar histology. Control of metastatic disease remains a formidable problem for patients with Stage IV RMS.     

Long-term survival of nasopharyngeal carcinoma following concomitant radiotherapy and chemotherapy

Purpose: The purpose of this study is to demonstrate long-term survival of nasopharyngeal carcinoma treated with concomitant chemotherapy and radiotherapy (CCRT) followed by adjuvant chemotherapy.

Methods and Patients: One hundred and seven patients with Stage III and IV (American Joint Committee on Cancer, AJCC, 1988) nasopharyngeal carcinoma (NPC) were treated with concomitant chemotherapy and radiotherapy (CCRT) followed by adjuvant chemotherapy between April 1990 and December 1997 in Koo Foundation Sun Yat-Sen Cancer Center, Taipei. The dose of radiation was 70 Gray (Gy) given in 35 fractions, 5 fractions per week. Two courses of chemotherapy, consisting of cisplatin and 5-fluorouracil, were delivered simultaneously with radiotherapy in Weeks 1 and 6 and two additional monthly courses were given after radiotherapy. According to the AJCC 1997 staging system, 32 patients had Stage II disease, 44 had Stage III, and 31 had Stage IV disease.

Results: With median follow-up of 44 months, the 5-year overall survival rate in all 107 patients was 84.1%, disease-free survival rate was 74.4%, and locoregional control rate was 89.8%. The 3-year overall survival for Stage II was 100%, for Stage III it was 92.8%, and for Stage IV, 69.4% (p = 0.0002). The 3-year disease-free survival for Stage II was 96.9%, for Stage III it was 87.7%, and for Stage IV it was 51.9% (p = 0.0001).

Conclusion: CCRT and adjuvant chemotherapy is effective in Taiwanese patients with advanced NPC. The prognosis of AJCC 1997 Stage II and III disease is excellent, but, for Stage IV (M0), it is relatively poor. Future strategies of therapy should focus on high-risk AJCC 1997 Stage IV (M0) cohort.     

A randomized trial comparing radiation therapy versus concomitant radiation therapy and chemotherapy in carcinoma of the thoracic esophagus.

From September 1982 to December 1985, 59 previously untreated patients with Stage II squamous cell carcinoma of the thoracic esophagus were randomly assigned to receive radiation therapy (RT) alone versus the concomitant use of RT and chemotherapy (CT) with 5-fluorouracil (5-FU), mitomycin C, and bleomycin (RT + CT). Thirty-one patients were randomized to the RT regimen and 28 to the RT + CT regimen. The complete local response rate was 58% for the RT group and 75% for the RT + CT group (P = 0.77). The median duration of response was 8 months for both groups. The overall 5-year survival rates were 6% and 16% (P = 0.16) for the RT and RT + CT groups, respectively. Acute toxicities were more pronounced in the RT + CT group. This clinical trial did not detect a difference in outcome with combined-technique therapy. This result must be interpreted with caution because of the small number of patients entered in this trial. Confirmation of the value or lack of value for combined therapy will require additional larger clinical trials.     

Cisplatin, adriamycin and cyclophosphamide combination chemotherapy of epithelial ovarian cancer

The chemotherapeutic effects of cisplatin + adriamycin + cyclophosphamide (PAC) on 50 epithelial ovarian cancers were compared with the effects of 5-fluorouracil + cyclophosphamide + mitomycin C (FAM) in 17 patients. The cumulative survival at 5 years was 61.1% in all patients, 62.5% in patients treated with PAC and 54.7% in patients treated with FAM. The 5-year survival rate was 100% in Stage I, 63.5% in Stage II, 40.1% in Stage III and 22.2% in Stage IV. Of 22 patients with Stage III and IV treated with PAC, 16 patients responded (8CRs + 8PRs). The median survival duration of the treated patients was 19 months. On the other hand, of 8 patients treated with FAM, only one patient responded (PR). The median survival duration was 7 months. These results indicated the effectiveness of PAC chemotherapy against advanced ovarian cancer. No severe toxicity was observed during treatment with PAC or FAM.     

Effect of pentoxifylline on radiation response of non-small cell lung cancer: a phase III randomized multicenter trial.

PURPOSES: The objectives of this prospective clinical trial were to determine whether pentoxifylline improves the radiation response and survival in patients with non-small cell lung cancer. MATERIALS AND METHODS: From July 1993 through October 1994, 64 patients with histologically confirmed Stage I, II and III non-small cell lung cancer were randomly divided into pentoxifylline (Pento)+Radiotherapy (RT) group and RT alone group. Out of the 64 patients, only 47 patients who had measurable tumors on chest X-ray views were analyzed and divided into Pento+RT group (n=27) and RT alone group (n=20). Total tumor dose of 65-70 Gy was delivered as conventional fractionated radiation schedules. Pento was given to the patients 3 x 400 mg/day with a daily dose of 1200 mg during RT. RESULTS: Complete response (CR), partial response (PR), and stable in Pento+RT group were three (11%), 13 (48%), and 11 (41%), respectively, as compared with corresponding values of three (15%), 13 (65%), and four (20%) in the RT alone group. The median time to relapse in the Pento+RT group was 11 months which was 2 months longer than for the RT alone group (P>0.05). All the patients in both groups showed lower than or equal to grade 2 dysphagia, odynophagia, pulmonary fibrosis, and pneumonitis. The median survival was 18 months in the Pento+RT group and 7 months in the RT alone group. The 1-year survival rate was 60% in the Pento+RT group and 35% in the RT alone group, the 2-year survival rate was 18% in the Pento+RT group and 12% in the RT alone group. But these differences were not statistically significant (P>0.05). CONCLUSION: We concluded that Pento is a modestly effective radiation response modifier and provide benefit in the treatment of non-small cell lung cancer.     

Long-term results of infusional 5-FU, mitomycin-C and radiation as primary management of esophageal carcinoma.

An analysis of the results of 90 patients with esophageal cancer treated prospectively with combined chemotherapy and radiation without surgery and with a median follow-up of 45 months is presented. Fifty-seven patients with Stage I or II disease received definitive treatment consisting of 6,000 cGy in 6 to 7 weeks and 5-FU (1,000 mg/m2/24 hr) as a continuous intravenous (IV) infusion for 96 hours, starting on days 2 and 29. Mitomycin C (10 mg/m2) was administered as a bolus injection on day 2. Thirty-three patients received palliative treatment (5,000 cGy plus above chemotherapy) for Stage III, IV, or otherwise advanced disease (extraesophageal spread, distant metastases, multiple primary tumors). Follow-up ranged from 1 month to 96 months. Overall median survival of Stage I and II patients was 18 months with 3- and 5-year actuarial survival of 29% and 18%, respectively, while the median disease specific survival was 20 months with an actuarial disease specific survival of 41% and 30% at 3 and 5 years, respectively. A multivariate analysis of sex, histology, tumor location, and tumor size on survival revealed that the effect of stage was highly significant (Stage I versus II, 73% versus 33% at 3 years, p = .01), whereas the effect of sex approached significance (females versus males, 57% versus 34% at 3 years, p = less than .1). The actuarially determined local relapse-free rate for Stage I and II patients at both 3 and 5 years was 70%. Multivariate analysis again indicated stage to be highly significant (Stage I versus II, 100% versus 60% at 3 years, p = less than .01), whereas sex approached significance (female versus male, 75% versus 66% at 3 years, p = .07). The pattern of failure may be altered with this treatment regimen from local to one dominated by distant metastases. Of 29 patients who have failed, 14 (48%) had any component of local failure, whereas 21 (72%) had a distant failure as a component of failure. The median survival of patients with Stage III or IV disease was 9 months and 7 months, respectively. Palliation in this group of patients with advanced disease was good as 77% were rendered free of dysphagia post-treatment, and 60% were without dysphagia until death with a median dysphagia-free duration of 5 months. Severe toxicities were uncommon and nearly all were transient. Eleven of 90 patients (12.2%) had severe acute toxicities, whereas only 3 patients (3.3%) developed significant late treatment-related complications requiring hospitalization for management.     

Preoperative concurrent chemoradiotherapy plus radical surgery for advanced squamous cell carcinoma of the oral cavity: an analysis of long-term results

Locoregionally advanced squamous cell carcinomas of the head and neck continue to be a major clinical problem. We demonstrated in 1996 that preoperative concurrent cisplatin- or carboplatin-based chemotherapy and radiotherapy plus radical surgery in advanced oral cancer had minimal toxicity, had high clinical tumor response rates, was well tolerated and produced impressive complete response rates and a high 5-year survival rate. The purpose of the present study was the long-term follow-up of this treatment regimen for advanced oral carcinoma. Forty-eight patients with squamous cell carcinoma of the oral cavity (including soft palate) were treated preoperatively with cisplatin- or carboplatin-based chemotherapy in combination with simultaneous irradiation to a target volume of 40 Gy, and 2-6 weeks later underwent curative surgery. All patients with advanced Stage II (n=7), Stage III (n=22) and Stage IV (n=19) were treated and followed for an average of 7.2 years (range: 61-144 months). The overall actuarial survival of all patients was 81.3% at 5 years and also at 10 years. Progression-free survival at both 5 and 10 years was 84.8% for all patients, and 85.7% for Stage II, 90.0% for Stage III, and 78.9% for Stage IV patients. Progression-free survival rates according to the histopathologic regression grade of primary tumor following preoperative chemoradiotherapy at 10 years were 40. 0% for Grade IIa, 88.9% for Grade IIb, 100% for Grade III, and 87.5% for Grade IV. Patients who achieved good responses histopathologically (Grades IIb, III, IV) had superior survival rates in comparison to patients with extensive residual tumor (Grade IIa) in surgically resected specimens (p=0.0012). A better histologic regression grade was also associated with a higher survival rate even in the long-term analysis. This treatment regimen for advanced oral cancer produced high clinical and pathologic complete response and survival rates with an acceptable acute toxicity profile and lack of late therapeutic complications. The long-term follow-up showed gratifying results even for advanced oral cancers without a substantial increase in distant metastasis and second primary malignancy.     

Medically inoperable stage I adenocarcinoma of the endometrium treated with radiotherapy alone

Definitive therapy for Stage I adenocarcinoma of the endometrium consists of total abdominal hysterectomy and bilateral salpingo-oophorectomy. Pre- and/or post-operative radiotherapy (RT) is employed in selected patients with poor prognostic factors such as poorly differentiated tumors or deep myometrial invasion by tumor. The results are reported of RT alone in 69 patients with Stage I adenocarcinoma of the endometrium who presented with severe, acute, and chronic medical illnesses which prevented surgical management of their disease. Sixty-three patients (91.3%) were obese or hypertensive. Twenty-seven patients (39.1%) had diabetes mellitus, 16 (23.2%) had congestive heart failure, and the remaining patients had such conditions as stroke (17.4%), coronary artery disease (15.9%), and recent myocardial infarction (13.0%). The median age for this group of patients was 72.0 years compared to 60.0 years for a concurrent group of 304 patients with Stage I adenocarcinoma of the endometrium treated at our institution with combined surgery and RT. RT consisted of intracavitary insertions alone (11 patients), intracavitary plus low dose external beam therapy (9 patients), and intracavitary therapy plus high dose external beam therapy (49 patients, definitive RT). Younger patients and those with poorly differentiated disease were treated more aggressively. The 5- and 10-year overall survival for all patients was 76.8 and 33.3%, respectively. The 5- and 10-year disease-free survival was 88.1 and 82.4%, respectively. The 5-year overall and disease-free survival for the group of 49 patients treated with definitive RT was 85.4% and 88.7% with 15/49 (30.6%) having poorly differentiated tumors. For the definitive therapy group, the 5- and 10-year disease-free survival was 94.3, 92.3, and 78.0% for grades I, II, and III, respectively. Analysis of patterns of failure showed that none of the patients failed in the pelvis alone. Two out of 11 (18.2%) receiving intracavitary therapy alone and 3/49 (6.1%) receiving definitive RT failed in the pelvis with simultaneous distant metastasis (DM). Three patients in the definitive RT group failed with DM only. Severe complications occurred in 8 patients (16%), all of whom received definitive RT.     

Treatment of childhood germ cell tumors. Review of the St. Jude experience from 1979 to 1988.

BACKGROUND. The outlook for patients with germ cell tumors was poor before the advent of effective chemotherapy. The authors assessed the outcome of treatment with multiagent chemotherapy (with or without radiation therapy) in children treated for germ cell tumors at St. Jude Children's Research Hospital (SJCRH). METHODS. Sixty children with germ cell tumors were treated between January 1979 and June 1988. Postsurgical treatment was based on tumor site, stage, and histology. Most patients received chemotherapy with vincristine, actinomycin-D, and cyclophosphamide (VAC), or a modified Einhorn regimen (cisplatin, bleomycin, and vinblastine [PVB]); in the absence of response to initial therapy, patients received alternating courses of VAC and PVB (VAC/PVB regimen). Exceptions were patients with Stage I testicular tumors (observation only) and ovarian germinomas (Stage I tumors measuring less than 10 cm, observation only; tumors larger than 10 cm or Stage II-III disease, radiation only; and Stage IV disease, VAC plus radiation). RESULTS. The estimated 5-year survival is 100% for patients with Stage I disease (n = 18), 87% for patients with Stage II (n = 8), 72% for Stage III (n = 25), and 56% for Stage IV (n = 9). Patients with testicular tumors of any stage or with Stage I-II ovarian tumors had 100% 5-year survival. Extragonadal tumors responded poorly to VAC alone with recurrent or progressive disease in eight of nine patients. Treatment for those tumors was changed to alternating courses of VAC and PVB, which failed in only one of seven patients. Nine of 19 patients with advanced ovarian tumors had disease recurrence with VAC; these patients then received PVB, which was effective in four cases. CONCLUSIONS. For patients with advanced germ cell cancers, intensification of therapy or the development of new approaches is necessary. In contrast, future trials in children with limited stage should focus on reducing acute and long-term toxicities.     

Relationship between CA 125 and progesterone production in women with ovarian carcinoma

CA 125 and steroid production is compared in a group of 48 women with ovarian epithelial carcinoma. The histologic types were I C (n = 20), II C (n = 5), III C (n = 11), or V (n = 12). The number of patients in Stage I was six; Stage II, 11; Stage III, 16; and Stage IV, 15. All patients were naturally or surgically postmenopausal. Blood samples were taken at the first admission to the hospital and 14 cases with large tumors were followed with monthly sampling during chemotherapy, and in 13 cases until a recurrence of the tumor. CA 125 and steroid production were analyzed using radioimmunoassay. The results show a high correlation between initial CA 125 and especially progesterone plasma concentration. Both decreases during chemotherapy parallel the shrinkage of the tumor and increase 1 to 4 months before recurrence. Progesterone and CA 125 together predicted all recurrences but none of the factors alone. The prognostic value for 5-year survival was somewhat higher for progesterone than CA 125. CA 125 correlated highly with sex hormone binding globulin (SHBG) and negatively with albumin. The correlation may be due to the intercorrelation with tumor burden.     

Doxorubicin for favorable histology, Stage II-III Wilms tumor: results from the National Wilms Tumor Studies

BACKGROUND: After randomized trials in the 1980s, doxorubicin (DOX) was added to dactinomycin plus vincristine as standard chemotherapy for patients who had Stage III Wilms tumor (WT) of favorable histology (FH). Double-agent chemotherapy was retained for patients with Stage II disease. In this study, the authors reevaluated the efficacy of DOX using extended follow-up and additional patients. METHODS: The relative risks (RR) (DOX vs. no DOX) of disease recurrence and mortality were estimated for patients with Stage II-III/FH WT who were enrolled in the third and fourth National Wilms Tumor Studies (NWTS-3 and NWTS-4). The risk of congestive heart failure (CHF) was estimated for all patients who received DOX. RESULTS: No statistically significant effects of DOX were found for patients with Stage II tumors. For patients with Stage III tumors, the 8 year recurrence-free survival (RFS) and overall survival (OS) rates for randomized patients on NWTS-3 were 84% and 89%, respectively, for patients who received DOX (n = 130) and 74% and 83%, respectively, for patients who did not receive DOX (n = 118). Including all patients with Stage III disease who received DOX (n = 678) and did not receive DOX (n = 138), the RRs of recurrence were 0.47 (P = 0.007) and 0.40 (P = 0.011), and local recurrence respectively, after adjustment for radiation therapy (RT) dose, whereas the RR of mortality adjusted for RT and study was 0.68 (P = 0.17). The 20-year risk of CHF after primary DOX treatment on NWTS-3 and NWTS-4 was 1.2%. CONCLUSIONS: The inclusion of data from nonrandomized patients yielded estimates of DOX treatment effects for Stage III/FH WT that were stronger, albeit more susceptible to bias, than reported previously. Despite a lower reported risk of CHF, conclusive evidence that frontline therapy with DOX definitively improves survival remains elusive.