Changes in the radiation treatment of cancer of the anus in Glasgow

The survival and complication rate of two groups of patients with carcinoma of anus were compared. The first group of 20 patients were treated between 1974 and 1983 by double plane implantation using radium or equivalent caesium needles and supplementary external beam radiotherapy to groin nodes if present. The second group of 26 patients were treated between 1984 and 1990 by external beam radiotherapy followed by a jig implant using afterloading iridium needles. 5-year survival was superior in the second group (73% vs. 40%) with a lower incidence of radiation-induced complications.     

Fractionated high-dose-rate brachytherapy in primary carcinoma of the nasopharynx

PURPOSE: A growing body of data suggests that local control in nasopharyngeal cancer (NPC) is related to the radiation dose administered. We conducted a single-institution study of high-dose radiotherapy (RT), which incorporated high-dose-rate (HDR) brachytherapy (BT). These results were analyzed together with data obtained from controls who did not receive BT. PATIENTS AND METHODS: The BT group comprised 42 consecutive patients of whom 29 patients were staged according to the tumor, node, metastasis system as T1 through 3, 13 patients were T4, and 34 patients were N+ disease. BT was administered on an outpatient basis by means of a specially designed flexible nasopharyngeal applicator, and the dose distributions were optimized. Treatment for T1 through 3 tumors comprised 60 Gy of external-beam radiotherapy (ERT) followed by six fractions of 3 Gy BT (two fractions per day). Patients with parapharyngeal tumor extension and/or T4 tumors received 70 Gy ERT and four fractions of 3 Gy BT. The no-BT group consisted of all patients treated from 1965 to 1991 (n = 109), of whom 82 patients had stages T1 through 3, 27 patients had T4, and 80 patients had N+ disease. Multivariate Cox proportional hazards analyses were performed by using the end points time to local failure (TTLF), time to distant failure (TTDF), disease-free survival (DFS), cause-specific survival (CSS), and the prognostic factors age, tumor stage, node stage, and grade. Because the overall treatment time varied substantially in the no-BT group, the dependence of local failure (LF) on the physical dose as well as the biologic effective dose (BED) corrected for the overall treatment time (OTT) (BEDcor10) was studied. RESULTS: The BT group had a superior 3-year local relapse-free rate (86% v 60%; univariate analysis, P = .004). Multivariate analysis showed hazards ratios for BT versus no-BT of 0.24 for TTLF (P = .003), 0.35 for TTDF (P = .038), 0.31 for DFS (P < .001), and 0.44 for CSS (P = .01). The best prognostic group consisted of patients with T1 through 3, N0 through 2b tumors treated with BT who attained a 5-year TTLF of 94% and CSS of 91%. In contrast, the worst prognostic group, i.e., 5-year TTLF of 47% and CSS of 24%, was composed of patients with T4 and/or N2c through 3 tumors who did not receive BT. CONCLUSION: High doses of radiation (73 to 95 Gy) can be administered to patients with NPC with minimal morbidity by means of optimized HDR-BT. The use of a BT boost proved to be of significant benefit, particularly in patients with T1 through 3, N0 through 2b disease. The steep dose-effect relationship seen for the physical dose and the BEDcor10 indicates that the results are dose related. The analysis has identified a poor prognostic group in whom treatment intensification with chemotherapy (CHT) is indicated.     

Biochemical outcome after radical prostatectomy, external beam radiation therapy, or interstitial radiation therapy for clinically localized prostate cancer

CONTEXT: Interstitial radiation (implant) therapy is used to treat clinically localized adenocarcinoma of the prostate, but how it compares with other treatments is not known. OBJECTIVE: To estimate control of prostate-specific antigen (PSA) after radical prostatectomy (RP), external beam radiation (RT), or implant with or without neoadjuvant androgen deprivation therapy in patients with clinically localized prostate cancer. DESIGN: Retrospective cohort study of outcome data compared using Cox regression multivariable analyses. SETTING AND PATIENTS: A total of 1872 men treated between January 1989 and October 1997 with an RP (n = 888) or implant with or without neoadjuvant androgen deprivation therapy (n = 218) at the Hospital of the University of Pennsylvania, Philadelphia, or RT (n = 766) at the Joint Center for Radiation Therapy, Boston, Mass, were enrolled. MAIN OUTCOME MEASURE: Actuarial freedom from PSA failure (defined as PSA outcome). RESULTS: The relative risk (RR) of PSA failure in low-risk patients (stage T1c, T2a and PSA level < or =10 ng/mL and Gleason score < or =6) treated using RT, implant plus androgen deprivation therapy, or implant therapy was 1.1 (95% confidence interval [CI], 0.5-2.7), 0.5 (95% CI, 0.1-1.9), and 1.1 (95% CI, 0.3-3.6), respectively, compared with those patients treated with RP. The RRs of PSA failure in the intermediate-risk patients (stage T2b or Gleason score of 7 or PSA level >10 and < or =20 ng/mL) and high-risk patients (stage T2c or PSA level >20 ng/mL or Gleason score > or =8) treated with implant compared with RP were 3.1 (95% CI, 1.5-6.1) and 3.0 (95% CI, 1.8-5.0), respectively. The addition of androgen deprivation to implant therapy did not improve PSA outcome in high-risk patients but resulted in a PSA outcome that was not statistically different compared with the results obtained using RP or RT in intermediate-risk patients. These results were unchanged when patients were stratified using the traditional rankings of biopsy Gleason scores of 2 through 4 vs 5 through 6 vs 7 vs 8 through 10. CONCLUSIONS: Low-risk patients had estimates of 5-year PSA outcome after treatment with RP, RT, or implant with or without neoadjuvant androgen deprivation that were not statistically different, whereas intermediate- and high-risk patients treated with RP or RT did better then those treated by implant. Prospective randomized trials are needed to verify these findings.     

Surgery versus surgery and postoperative radiotherapy in squamous cell carcinoma of the buccal mucosa: a comparative study

BACKGROUND: The efficacy of postoperative radiotherapy for squamous cell carcinoma of the buccal mucosa was evaluated. METHODS: One hundred seventy-six patients treated between 1989 and 1993 were analyzed. One hundred fifteen patients were treated with surgery alone (Group 1), and 61 patients were treated with a combination of surgery and postoperative radiotherapy (Group 2). RESULTS: Actuarial 3-year locoregional control in Groups 1 and 2 was 11% and 48% for patients with stage III + IV cancer (P = .001) and 71% and 75% for patients with stage I + II cancer (P = .74), respectively. On multivariate analysis for locoregional failure, surgical margin, bone invasion, high grade, and node involvement were significant factors in Group 1, whereas in Group 2 only tumor thickness was a significant factor. For local failure, margin, bone invasion, and stage in Group 1 and tumor thickness in Group 2 appeared as significant factors. For nodal failure, clinical nodal (cl N0 vs. N+) stage and grade in Group 1 and pathologic nodal stage (pN0 + 1 vs. pN2) in Group 2 were observed as significant factors. On subset analysis, postoperative radiotherapy was observed to have a significant advantage for surgical margins of 2 mm or less in both early pT (T1 + T2) (P = .019) and late pT (T3 + T4) (P = .016) stages. The local failure rate was higher if the time between surgery and radiotherapy was greater than 30 days. CONCLUSIONS: Postoperative radiotherapy was effective in decreasing locoregional failure in patients with close surgical margins, tumor thicker than 10 mm, high-grade tumors, positive node, and bone invasion. The effect of interval between surgery and postoperative radiotherapy on local failure was margin-dependent.     

Preliminary report of the Asian-Oceanian Clinical Oncology Association randomized trial comparing cisplatin and epirubicin followed by radiotherapy versus radiotherapy alone in the treatment of patients with locoregionally advanced nasopharyngeal carcinoma. Asian-Oceanian Clinical Oncology Association Nasopharynx Cancer Study Group

BACKGROUND: The aim of this trial was to compare the outcome achieved with neoadjuvant chemotherapy followed by radiotherapy to that achieved with radiotherapy alone for patients with locoregionally advanced undifferentiated or poorly differentiated nasopharyngeal carcinoma (NPC) meeting one of the following criteria: Ho's T3 disease, Ho's N2-N3 disease, or lymph node size > or =3 cm. METHODS: Between September 1989 and August 1993, 334 patients were enrolled in the study, with equal numbers of patients randomized to the neoadjuvant chemotherapy arm (CT arm) and the radiotherapy arm (RT arm). Neoadjuvant chemotherapy consisting of 2-3 cycles of cisplatin (60 mg/m2 on Day 1) and epirubicin (110 mg/m2 on Day 1) followed by radiotherapy was given to the CT arm. For radiotherapy, a dose of 66-74 gray (Gy) (median, 71 Gy) was delivered to the primary tumor and 60-76 Gy (median, 66 Gy) to the neck. Two hundred eighty-six eligible patients completed the treatment and were evaluable for treatment response (134 in the CT arm, 152 in the RT arm). All patients were included in the survival analysis based on the intention to treat. The median follow-up was 30 months for the whole cohort and 41 months for the surviving patients. RESULTS: Analysis of the 334 patients based on the intention to treat showed no significant difference in relapse free survival (RFS) or overall survival (OS) between the 2 treatment arms (3-year RFS rate: 48% in the CT arm vs. 42% in the RT arm, P = 0.45; 3-year OS rate: 78% vs. 71%, P = 0.57). In an efficacy analysis based on only the 286 evaluable patients, a trend of improved RFS favoring the CT arm was observed (3-year RFS rate: 58% vs. 46%, P = 0.053), with again no significant difference in OS (3-year OS rate: 80% vs. 72%, P = 0.21). In the subgroup of 49 patients with bulky neck lymph nodes >6 cm, improved RFS (3-year RFS rate: 63% vs. 28%, P = 0.026) and OS (3-year OS rate: 73% vs. 37%, P = 0.057) were observed, favoring the CT arm. CONCLUSIONS: This multicenter randomized study did not demonstrate any benefit with the addition of cisplatin-epirubicin neoadjuvant chemotherapy for patients with locoregionally advanced nasopharyngeal carcinoma; therefore routine administration of neoadjuvant chemotherapy to this target group cannot be recommended. Although the overall incidence of recurrence was reduced with the addition of chemotherapy in the efficacy analysis, the overall survival was not affected. A more effective chemotherapy regimen, the selection of an appropriate target group, and the use of an alternative strategy for combining chemoradiotherapy should be explored in future trials.     

Carcinoma of the tonsillar fossa: prognostic factors and long-term therapy outcome

PURPOSE: To identify prognostic parameters and evaluate the therapeutic outcomes for patients with carcinoma of the tonsillar fossa treated with three treatment modalities. METHODS AND MATERIALS: The results of therapy are reported in 384 patients with histologically proven epidermoid carcinoma of the tonsillar fossa; 154 were treated with irradiation alone (55-70 Gy), 144 with preoperative radiation therapy (20-40 Gy), and 86 with postoperative irradiation (50-60 Gy). The operation in all but four patients in the last two groups consisted of an en bloc radical tonsillectomy with ipsilateral lymph node dissection. RESULTS: Treatment modality and total irradiation doses had no impact on survival. Actuarial 10-year disease-free survival rates were 65% for patients with T1 tumors, 60% for T2, 60% for T3, and 30% for T4 disease. Patients with no cervical lymphadenopathy or with a small metastatic lymph node (N1) had better disease-free survival (60% and 70%, respectively) at 5 years than those with large or fixed lymph nodes (30%). Primary tumor recurrence (local, marginal) rates in the T1, T2, and T3 groups were 20-25% in patients treated with irradiation and surgery and 31% for those treated with irradiation alone (difference not statistically significant). In patients with T4 disease treated with surgery and postoperative irradiation, the local failure rate was 32% compared with 86% with low-dose preoperative irradiation and 47% with irradiation alone (p = 0.03). The overall recurrence rates in the neck were 10% for N0 patients, 25% for N1 and N2, and 35-40% for patients with N3 cervical lymph nodes, without significant differences among the various treatment groups. The incidence of contralateral neck recurrences was 8% with the various treatment modalities. On multivariate analysis the only significant factors for local tumor control and disease-free survival were T and N stage (p = 0.04-0.001). Fatal complications were noted in 7 of 144 (5%) patients treated with preoperative irradiation and surgery, 2 of 86 (2%) of those receiving postoperative irradiation, and 2 of 154 (1.3%) patients treated with radiation therapy alone. Other moderate or severe nonfatal sequelae were noted in 30% of the patients treated with preoperative irradiation and surgery, in 53% treated with postoperative irradiation, and in 19% receiving radiation therapy alone. CONCLUSION: Primary tumor and neck node stage are the only significant prognostic factors influencing locoregional tumor control and disease-free survival. Treatment modality had no significant impact on outcome. Radiation therapy remains the treatment of choice for patients with stage T1-T2 carcinoma of the tonsillar fossa. In patients with T3-T4 tumors and good general condition, combination surgery and postoperative irradiation offers better tumor control than single-modality and preoperative irradiation procedures, but with greater morbidity.     

Organ-preserving therapy in invasive bladder carcinoma]

With the aim of organ preservation, transurethral resection with subsequent radiotherapy (until 1985) or combined radio- and chemotherapy (since 1986) was undertaken as part of a prospective trial in 175 consecutive patients (137 men, 38 women; mean age 65 [31-90] years) with invasive bladder carcinoma, tumour stage T1-4 N0-3 M0. All patients had a transurethral resection, followed 2-6 weeks later by definitive radiotherapy at a dose of 50.4 Gy to the bladder in 28 fractions. 85 patients simultaneously with the radiotherapy received chemotherapy with cisplatin (25 mg/m2 daily) or carboplatin (65-75 mg/m2 daily) in the first and fifth weeks of radiotherapy. The 5-year survival rate for the whole group (including inoperable cases) was 50%. The survival rate as related to the T category was 53% for T1 (n = 26), 68% for T2 (n = 34), 45% for T3 (n = 94) and 22% for T4 (n = 17). 139 patients (79%) were left with a normally functioning bladder. Cystectomy was performed in 36 patients because of remaining tumour or recurrence after radiotherapy. Combined radio- and chemotherapy improved the histological remission rate, compared with an earlier control group with radiotherapy only, but it did not affect the survival rate. These data indicate that in advanced bladder carcinoma organ-preserving treatment with transurethral resection and definitive radiotherapy or combined radio- and chemotherapy can be successful.     

Nonnasopharyngeal lymphoepithelioma of the head and neck

BACKGROUND: Lymphoepithelioma (squamous cell carcinoma with associated lymphoid stroma) commonly occurs in the nasopharynx, rarely at other sites. As a result, the clinical course and optimal treatment of nonnasopharyngeal lymphoepithelioma of the head and neck have not been well described. This retrospective study was undertaken to analyze the clinical course of the disease in patients treated at a single institution and to formulate recommendations for treatment based on that experience as well as results reported in the literature. METHODS: Between 1950 and 1994, 34 patients with nonnasopharyngeal lymphoepithelioma of the head and neck were treated at the University of Texas M. D. Anderson Cancer Center. The patients' medical records were reviewed and their pathologic specimens evaluated. The primary tumor sites were: oropharynx (24 patients), salivary gland (4), laryngohypopharynx (4), and the maxillary sinus/nasal cavity (2). Assessed in accordance with the 1992 American Joint Committee Against Cancer TNM staging system, T classifications were TX-2, T1-7, T2-8, T3-10, and T4-7, and N classifications were N0-8, N1-5, N2-15, and N3-6. Treatment consisted of radiotherapy for 24 patients, excisional biopsy of the primary tumor followed by radiotherapy for 7 patients, and surgery for 3 patients. Of the patients treated with radiotherapy, neck dissections were performed on only two, both of whom had persistent lymph node masses after completing radiotherapy. The median dose delivered to the primary tumor was 65 gray (Gy) (range, 46-78 Gy). The median fraction size was 2.1 Gy (range, 1.6-3.2 Gy). RESULTS: The 5-year actuarial disease specific survival and overall survival rates were 59% and 39%, respectively. The 5-year actuarial local control rate for all patients was 94%. For the irradiated patients, the 5-year regional control rates were 77% overall and 83% within the radiation field. The 5-year actuarial rate of distant metastasis for all patients was 30%. For patients who presented with and without regional adenopathy, the 5-year rates of distant metastasis were 36% and 12%, respectively (P = 0.27). CONCLUSIONS: Nonnasopharygeal lymphoepithelioma is a radiosensitive disease. High rates of locoregional tumor control were achieved with radiotherapy at all head and neck sites. The main cause of treatment failure was distant metastasis, which occurred more frequently in patients with lymph node involvement. Radiotherapy is appropriate initial locoregional therapy for patients with this disease. Surgery should be reserved for patients who have persistent disease after completing radiotherapy. Systemic therapy is a reasonable approach for patients who present with regional adenopathy because they have a relatively high rate of distant metastasis.     

Management for stage II glottic carcinoma: radiation therapy or surgery

AIM: To analyze the results of stage II glottic carcinoma treated with radiotherapy or surgery. PATIENTS AND METHOD: One hundred thirty-four patients with squamous cell carcinoma of the T2N0M0 glottic carcinoma treated at the Osaka Medical Center for Cancer and Cardiovascular Diseases from 1979 through 1991 were reviewed. The 5-year disease-free survival and laryngeal preservation rate and prognostic factors were examined. Treatment was radiation therapy with salvage surgery for failure or surgery alone. RESULTS: The 5-year disease-specific survival rate for the radiotherapy group was 100% and for the surgery group, 93% (p = 0.055). In the surgery group 5-year disease-specific survival rate for the subgroup of cord mobility was 94% and that of impaired cord mobility, 89% (p = 0.5354). Concerning laryngeal preservation the radiotherapy group showed better preservation rate than the surgery group in the subgroup of cord mobility, i.e., 41/51 (80%) versus 6/55 (11%) (p < 0.001) although significant difference was not observed in the lesion with impaired cord mobility, 2/5 versus 4/22 (p = 0.171). CONCLUSION: We recommend radiation therapy for stage II glottic carcinoma with normal cord mobility, although further study is needed to improve the preservation rate of the larynx with keeping the disease-specific survival for the lesion with impaired cord mobility.     

The management of deeply infiltrating (T3) bladder carcinoma: controlled trial of radical radiotherapy versus preoperative radiotherapy and radical cystectomy (first report)

The preliminary results are presented of a multicentre, co-operative randomised trial, sponsored by the Institute of Urology, London, in which radical irradiation (6,000 rads in 6 weeks) is compared with preoperative irradiation (4,000 rads in 4 weeks) plus radical cystectomy for deeply infiltrating carcinoma of the bladder (Stage T3 or B2C). 189 of the 199 cases entered into the trial between 1966 and 1975 were eligible for study. The overall 3- and 5-year survival rates for combined treatment were 41% and 33%, respectively, compared with 28% and 21% for radical radiotherapy. The operative mortality was 7.8%. The difference between the two treatments in favour of the combined treatment has not yet reached the generally accepted level of significance (P less than 0.05), the p factors for the 3- and 5-year results being 0.064 and 0.077, respectively. Of patients receiving the protocol combined treatment, reduction in tumour stage was found in the surgical specimen in 47% of cases. The overall incidence of nodal metastases was 23% (against the usual figure of 40-50%), and in the presence of a good response of the primary tumour to irradiation, only 8%. The 3- and 5-year survival rates for the down-staged cases were 66% and 55%, respectively, compared with 29% and 22% for patients showing no stage reduction in the surgical specimen. The aim of our future studies is to find effective radiosensitising and cytotoxic agents with which to try and increase the incidence and degree of tumour response to pre-operative irradiation in the combined modality treatment of T3 bladder cancers.     

Whole abdominal external beam radiation in the treatment of primary carcinoma of the fallopian tube

Thirty-two patients with adenocarcinoma of the fallopian tube, treated between 1975 and 1990, were studied. Thirteen patients had stage I disease, 9 stage II, and 10 stage III. All patients underwent bilateral salpingo-oophorectomy, total abdominal hysterectomy, and subcolic omentectomy. All patients received postoperative primary whole abdominal external beam radiotherapy. Seventeen patients (53.1%) of the treated group survived NED for at least 5 years. Survival was 76.9% for stage I, 55.6% for stage II, and 20% for stage III. In the Cox multivariate analysis, two variables were independently related to survival: stage of disease and size of residual disease after surgery. Postoperative teleradiotherapy was totally ineffective in gross residual (>2 cm in diameter) disease (0% 5-year NED survivors) and not effective enough in small residual disease (<2 cm in diameter) (33% 5-year NED survivors). Despite postoperative whole abdominal external beam radiotherapy, 3 patients with microscopic, 4 with small, and 4 with gross residual disease did fail within the peritoneal cavity.     

Results of surgical treatment of T3 lung carcinoma according to the combined resection of involved organs

A new TNM staging system was decided last year by UICC, consequently T3N0M0 was transferred from stage IIIA to stage IIB. Although T3 is defined to include tumors with direct invasion to adjacent organs. Those are chest wall, parietal pleura, diaphragma and pericardium, however results of surgical treatment according to the combined resection of involved organs described above have not been investigated yet enough. Eighty-nine cases with T3 from 1996 were divided into two groups, patients from 1986 to 1990 and from 1994 to 1998. In the former phase 46 cases were resected and its 5-year survival rate was 15.6%. Better prognosis with significant difference was shown in patients between N0 (5-year survival: 25.1%) and N1 + N2 (5-year survival: 4.0%). In the latter phase 43 cases underwent surgery and its 3-year survival was 24.0%. In the prognoses according to the involved adjacent organs, patients with combined resection of parietal pleura showed the best survival in comparison with patients of chest wall resection and pericardial resection, but there was no significant difference in these 3 groups. Two patients with combined resection of diaphragma are well alive.     

A phase II trial and pharmacokinetic analysis of 96-hour infusional paclitaxel in patients with metastatic colorectal cancer

AIMS: To carry out a retrospective study of male breast cancer over a 22-year experience. METHODS: Data from 121 male patients with breast cancer treated between the years 1972 and 1994 at the Surgical Clinic of Ankara Oncology Hospital were reviewed. Distribution of cases according to stage was: 2.5% stage I, 28.9% stage II, 55.4% stage III and 13.2% stage IV (AJCC staging method). The surgical treatment for 23 of the patients (19%) was Halsted's radical mastectomy or modified radical mastectomy. Seventy-three cases (60.3%) had total mastectomy without axillary node dissection and 25 (20.7%) had local tumour excision only. Seventy-two of 121 patients had adjuvant treatment. RESULTS: In general the prognosis of men with breast cancer was worse than for women. In the analysis of patients in stages I, II and III-A (operable disease group), the 5-year survival rates were 73% in axillary node-negative patients and 77% in those with tumours sized under 5 cm (P<0.001). In these patients, univariate analysis demonstrated that axillary status (relative risk of death in positive status vs. negative=3.6), tumour size (relative risk in T3 vs. T1-2=2), surgical treatment type (relative risk in simple mastectomy vs. radical mastectomy=1.9) and adjuvant chemotherapy (relative risk if no chemotherapy=1.4) were statistically significant factors associated with survival. CONCLUSIONS: Cox's regression model revealed that axillary status, tumour size and type of surgical treatment were the most important independent prognostic factors (P<0.001).     

Stage I rectal cancer: identification of high-risk patients

BACKGROUND: Stage I rectal cancer (T1, T2 N0) is currently treated by surgical resection alone. Despite adequate surgical resection, approximately 10-15% of patients will develop recurrence. Identification of patients at high risk for recurrence could potentially lead to an improvement in outcome by selection of these patients for adjuvant therapy. METHODS: Between June 1986 and September 1996, 211 patients with primary rectal cancer (stage I) were treated by radical surgical resection alone. The medical data of all patients were entered into a database and prospectively followed. The following 10 prognostic factors were correlated with recurrence and tumor-related mortality: patient factors: age, gender, and preoperative carcinoembryonic antigen level; tumor factors: location from the anal verge (< 6 cm vs. > or = 6 cm), T stage (T1 vs. T2), intratumoral blood vessel invasion (BVI), intratumoral lymphatic vessel invasion, presence of tumor ulceration, and histologic differentiation; and treatment-related factors: extent of surgical resection--abdominal perineal resection versus low anterior resection. Univariate analysis of the effect of the prognostic factors on recurrence and tumor-related mortality were performed by the method of Kaplan-Meier and log rank test. Independent prognostic factors were determined by a multivariate analysis performed using the Cox proportional hazards model. RESULTS: The overall 5-year actuarial recurrence was 12% and tumor-related mortality was 10%. Independent predictors of recurrence were male gender and BVI. Independent predictors of tumor-related mortality were male gender, BVI, and poorly differentiated tumors. CONCLUSIONS: Despite radical resection, patients with stage I rectal cancer with male gender, BVI, and poorly differentiated tumors should be considered high-risk patients.     

P53 overexpression in head and neck carcinoma and radiotherapy results

PURPOSE: P53 gene mutations are the common genetic changes encountered in human cancers, and there is extensive evidence that the P53 status may determine tumor response to therapy. This study was carried out to investigate whether there is any correlation between accumulation (overexpression) of P53 protein and poor prognosis in patients with head and neck carcinomas treated with radical radiotherapy. METHODS AND MATERIALS: Seventy-nine patients with head and neck carcinomas who were diagnosed and treated in 1989-90 with curative radiotherapy were studied retrospectively. Paraffin sections from archival material were studied using immunohistochemical staining (IHC) with mouse monoclonal antibodies (D0-7) to human P53 protein. Univariate and multivariate analysis of loco-regional tumor control and patient survival were performed on possible prognostic factors. RESULTS: Forty-two (53%) patients showed positive IHC staining in their tumors. Fifty-three percent of the laryngeal, 64% of the oropharyngeal, and 43% of the oral cavity carcinomas showed P53 overexpression. All tumor specimens with vascular, lymphatic, and/or sarcolemmal invasion showed P53 overexpression. The proportion of tumor-stained nuclei was higher in the poorly differentiated than in the well and moderately differentiated tumors (p < 0.05), but there was no correlation with the patient overall or disease-free 5-year actuarial survival. There was no difference in the 5-year actuarial survival and disease-free survival between patients with P53 immunostaining in their tumors and those with no immunostaining (59% vs. 65% and 57% vs. 51%, respectively). The TNM tumor stage was the most significant prognostic factor with 5-year actuarial survival of 87% for early and 14% for late stages (p < 0.0001). There was a significant correlation between immunostaining and history of smoking (p = 0.02). CONCLUSION: The data demonstrate that the P53 accumulation as detected by immunohistochemical staining in a group of head and neck carcinomas was not predictive of patient's poor survival or disease-free survival. Multivariate statistical analysis showed that the TNM tumor stage was the only significant prognostic factor. There was a significant association between P53 accumulation and smoking.     

Concurrent carboplatin/5FU and radiotherapy compared to radiotherapy alone in locally advanced cervical carcinoma: a case-control study

AIMS AND BACKGROUND: Despite the introduction of innovative techniques in radiotherapy (RT) delivery, no significant improvement in survival has been achieved in the last decades. Concurrent chemoradiation therapy (CRT) is one of the several avenues being explored to improve the results. METHODS AND STUDY DESIGN: Twenty-eight women with locally advanced squamous cell carcinoma of the uterine cervix were treated with CRT comprising a combination of external and intracavitary RT, along with 3 cycles of 5-fluorouracil (5-FU) and carboplatin. Toxicity, pelvic control rate and disease-free survival achieved in this group of patients were compared in a case-control study with those of a group of 28 patients with similar clinico-pathologic characteristics treated with radical RT alone at our institution. RESULTS: CRT was well tolerated, with 97% of the patients completing the protocol as planned. Acute toxicity, primarily hematologic, was significantly (P = 0.05) higher in the cases than in the controls (25% vs 3%). One treatment-related death occurred in a stage III patient in the CRT group. The median follow-up was 55 months (range, 20-156) in the RT group and 20 months (range, 14-46) in the CRT group. Pelvic control rate, disease-free survival and overall survival were not significantly different in the two groups. Estimated 5-year survival rate was 70% and 66% respectively for the RT and CRT group. CONCLUSIONS: Concomitant carboplatin/5-FU and radiotherapy is a safe and tolerable means of treatment for locally advanced cervical cancer. In our study, however, concurrent CRT did not result in a significant improvement in pelvic control rate or survival compared to standard conventional radiotherapy.     

Wedge resection versus lobectomy for stage I (T1 N0 M0) non-small-cell lung cancer

BACKGROUND: The role of nonanatomic wedge resection in the management of stage I (T1 N0 M0) non-small-cell lung cancer continues to be debated against the present gold standard of care--anatomic lobectomy. METHODS: We analyzed the results of 219 consecutive patients with pathologic stage I (T1 N0 M0) non-small-cell lung cancer who underwent open wedge resection (n = 42), video-assisted wedge resection (n = 60), and lobectomy (n = 117) to assess morbidity, recurrence, and survival differences between these approaches. RESULTS: There were no differences among the three groups with regard to histologic tumor type. Analysis demonstrated the wedge resection groups to be significantly older and to have reduced pulmonary function despite a higher incidence of treatment for chronic obstructive pulmonary disease when compared with patients having lobectomy. The mean hospital stay was significantly less in the wedge resection groups. There were no operative deaths among patients having wedge resection; however, a 3% operative mortality occurred among patients having lobectomy (p = 0.20). Kaplan-Meier survival curves were nearly identical at 1 year (open wedge resection, 94%; video-assisted wedge resection, 95%; lobectomy, 91%). At 5 years survival was 58% for patients having open wedge resection, 65% for those having video-assisted wedge resection, and 70% for those having lobectomy. Log rank testing demonstrated significant differences between the survival curves during the 5-year period of study (p = 0.02). This difference was a result of a significantly greater non-cancer-related death rate by 5 years among patients having wedge resection (38% vs 18% for those having lobectomy; p = 0.014). CONCLUSION: Wedge resection, done by open thoracotomy or video-assisted techniques, appears to be a viable "compromise" surgical treatment of stage I (T1 N0 M0) non-small-cell lung cancer for patients with cardiopulmonary physiologic impairment. Because of the increased risk for local recurrence, anatomic lobectomy remains the surgical treatment of choice for patients with stage I non-small-cell lung cancer who have adequate physiologic reserve.     

Randomized clinical trial on the combination of preoperative irradiation and surgery in the treatment of adenocarcinoma of gastric cardia (AGC)--report on 370 patients

PURPOSE: An attempt was made to define the role of radiotherapy before operation for AGC. METHODS AND MATERIALS: From January 1978 to May 1989, a prospective randomized trial on preoperative radiotherapy (R+S) vs. surgery alone (S) for AGC was carried out in 370 patients. Patients were randomized into a combined group (R+S, 171 patients) or a surgery alone group (S, 199 patients) by the envelope method. 8-MV photon or telecobalt was used for the preoperative radiation therapy, using anterior-posterior opposing parallel fields to deliver 40 Gy to the cardia, lower segment of the esophagus, fundus, lesser curvature, and hepatogastric ligament. Surgery was performed after 2 to 4 weeks rest. RESULTS: The 5- and 10-year survival rates of the R+S Group and the S Alone Group were 30.10% and 19.75%, 20.26% and 13.30%, respectively. The survival curves of these two groups diverged right from the beginning after the operation over the ninth year. Statistics by Kaplan-Meier log rank test proves that the difference is significant (chi2 = 6.74, p = 0.0094). The immediate results were: resection rate 89.5% and 79.4% (p < 0.01); pathologic stage after resection T2 12.9% and 4.5% (p < 0.01), T4 40.3% and 51.3% (p < 0.05), lymph node metastasis rates 64.3% and 84.9% (p < 0.001); operative mortality rates 0.6% and 2.5%; intrathoracic leak rates 1.8% and 4.0%, respectively. The causes of failure were: local uncontrol and recurrence 38.6% vs. 51.7% (p < 0.025), regional lymph node metastasis 38.6% vs. 54.6% (p < 0.005), distant metastasis 24.3% vs. 24.7%. CONCLUSION: Preoperative radiation therapy is able to improve the results of surgery for adenocarcinoma of the gastric cardia.     

Prognostic factors in muscle-invasive bladder cancer treated with radiotherapy: an immunohistochemical study

OBJECTIVE: To determine the prognostic role of p53, Ki-67 and p21 for patients with muscle-invasive bladder cancer treated with curative intent by radiotherapy. PATIENTS AND METHODS: The study included 131 patients (24 women and 107 men, median age 72 years, range 40-86) with transitional cell carcinoma (T2-T4) treated with external definitive pelvic radiotherapy between 1985 and 1994. Paraffin-embedded pretreatment biopsies from the patients were examined for the presence of p53, p21 and Ki-67, detected by immunohistochemistry, and related to tumour stage, grade and patient survival. RESULTS: The expression of p53 protein correlated positively with the detection of Ki-67 (P < 0.05) but did not correlate with p21. None of the immunohistochemical variables (p53, p21 or Ki-67) correlated with T category and only Ki-67 correlated with histological grade. Patients with > 5% p21 expression tended to live longer than those with < 5% (P = 0.09). In a multivariate analysis, the T category (T2/T3 vs. T4), histological grade (2 vs. 3) and p21 expression (< or = 5% vs. > 5%) were independent prognostic factors for overall survival. CONCLUSION: Further investigation is warranted in patients with muscle-invasive bladder cancer undergoing different types of treatment p21 seems to play an independent prognostic role in these patients, in addition to T category and grade.     

Surgical management of early-stage hypopharyngeal carcinoma

There is little consensus regarding the extent of surgical ablation that is needed to attain cure in early-stage hypopharyngeal carcinoma (HPC). To determine effective surgical management of early-stage HPC, we retrospectively reviewed all cases of stage I or stage II HPC treated at our institution between 1970 and 1992. Of 305 patients identified with HPC, 50 (16%) had stage I (N = 13) or stage II (N = 37) cancer at diagnosis. Thirty-seven of the 50 (74%) underwent surgery alone or combined with preoperative or postoperative radiotherapy (RT). Patients were divided into three surgical groups. Group 1 underwent partial pharyngectomy (N = 9), group 2 underwent total laryngectomy and partial pharyngectomy (N = 17), and group 3 underwent total laryngopharyngectomy with cervical esophagectomy and reconstruction (N = 11). Overall and disease-specific survivals were determined from Kaplan-Meier survival analysis. Disease-free 5-year survival in stage I and II HPCs was 40.1%. Univariate analysis showed a statistically significant decrease in survival for patients undergoing partial pharyngectomy when compared with those undergoing more extensive procedures (p < .03). This was confirmed with multivariate loglogistic regression analysis (p < .03) correcting for confounding variables of site and RT. These data suggest that wide resection improves disease-free survival in patients with early-stage HPC.