The role of elective para-aortic lymph node irradiation in patients with locally advanced cervical cancer.

AIMS: Pelvic lymph node positivity in cervical cancer is known to be an adverse prognostic factor and is associated with an elevated risk of clinically occult para-aortic lymph node metastases. The purpose of this study was to examine the benefit of elective para-aortic lymph node radiotherapy (PART) in patients with no clinical or radiographic evidence of para-aortic lymph node metastases receiving concurrent cisplatin chemotherapy. MATERIALS AND METHODS: Patients treated with radiotherapy and concurrent cisplatin for cervical cancer from 1999 to 2009 were identified in two prospective databases. All patients received external beam pelvic radiotherapy (PRT) to a median dose of 50 Gy concurrently with weekly cisplatin 40 mg/m(2). This was followed by pulse dose rate intracavitary brachytherapy to a median dose of 40 Gy. Patients at high risk of occult para-aortic metastases also received PART to a median dose of 40 Gy. RESULTS: There were 228 patients suitable for analysis; the median follow-up was 4.6 years. The addition of PART to PRT was not associated with a significant difference in disease-free survival (hazard ratio 1.1, confidence interval 0.7-1.8, P = 0.75) or overall survival (hazard ratio 1.6, confidence interval 0.9-2.7, P = 0.11) on multivariate analysis. There was no significant difference in the rate of para-aortic relapse with PART versus PRT (hazard ratio 2.01, confidence interval 0.79-5.12, P = 0.14). The 3 year grade 3-4 late toxicities were 11% for the PART group versus 8% for PRT (hazard ratio 1.39, confidence interval 0.58-3.37, P = 0.47). CONCLUSIONS: These results suggest that cervical cancer patients treated with radiotherapy and concurrent cisplatin do not benefit from elective PART.

A hypofractionated radiotherapy regimen (0-7-21) for advanced gynaecological cancer patients.

AIMS: To evaluate the efficacy of a palliative three fraction radiation regimen delivered on days 0, 7 and 21 (0-7-21 regimen) for advanced stage gynaecological cancer patients. MATERIALS AND METHODS: Fifty-one patients with advanced gynaecological cancer who were treated with the 0-7-21 regimen between 1998 and 2008 were identified. The median follow-up period was 1.4 months (range 0.2-33.4). Treatment completion data, symptomatic response, toxicity and survival were retrospectively analysed. RESULTS: Forty-eight patients received at least two of the three planned fractions. Complete and partial responses of vaginal bleeding were seen in 92% of 26 evaluable patients. Complete and partial responses of pain were seen in 76% of 25 evaluable patients. Eighteen of the 33 evaluable patients experienced grade 1/2 acute toxicity. No patients experienced grade 3/4 toxicity. Grade 1/2 and grade 3 late toxicity occurred in four and one of 12 evaluable patients, respectively. Grade 5 toxicity was assigned in two patients. It was uncertain whether these deaths were radiation related or due to tumour progression. Eleven patients survived longer than 12 months. CONCLUSIONS: The 0-7-21 regimen provided effective and rapid symptomatic relief with acceptable toxicity, and offered the advantage of convenience for most patients. It offers an alternate treatment option for carefully selected patients with incurable gynaecological malignancies.

Uterine papillary serous carcinoma: evaluation of multimodality treatment with abdominopelvic radiotherapy and chemotherapy.

The aim of this study was to compare overall survival (OS), progression-free survival (PFS), and relapse patterns between different modalities of treatment for uterine papillary serous carcinoma (UPSC). A retrospective review of 124 patients with pathologically confirmed UPSC was performed, of whom, 97 patients were eligible for study. Postoperative treatment groups included adjuvant radiotherapy consisting of whole abdomen and a pelvic boost (abdominopelvic radiotherapy [APRT]) (55 patients), paclitaxel and carboplatin chemotherapy (CT) for six cycles followed by APRT (18 patients), CT only (5 patients), and 19 patients were observed without postoperative adjuvant therapy. Three-year OS was 81% and 63% for the CT followed by APRT and APRT alone, respectively (P= 0.11). After controlling for stage, the group treated with APRT alone had significantly decreased OS and PFS compared to the CT/APRT group (HR 3.6; 1.3-9.8; P= 0.01) and (HR 2.9; 95% CI 1.1-7.3; P= 0.03), respectively. Within the limitations of a retrospective study, the results of this study indicate that multimodality postoperative treatment with paclitaxel and a platinum-based CT followed by APRT may increase the survival of patients with UPSC. However, further prospective studies using these combined modalities are needed to confirm these findings.

Tumor hypoxia has independent predictor impact only in patients with node-negative cervix cancer.

PURPOSE: This prospective clinical study was begun in 1994 to validate the independent prognostic impact of tumor hypoxia in patients with cervix cancer treated with definitive radiation therapy. PATIENTS AND METHODS: Between May 1994 and January 1999, 106 eligible patients with epithelial cervix cancer had tumor oxygen pressure (PO(2)) measured using the Eppendorf probe. Oxygenation data are presented as the hypoxic proportion, defined as the percentage of PO(2) readings less than 5 mm/Hg (abbreviated as HP(5)) and the median PO(2). RESULTS: The median HP(5) in individual patients was 48%, and the median PO(2) was HP(5). Progression-free survival (PFS) for patients with hypoxic tumors (HP(5) > 50%) was 37% at 3 years versus 67% in those patients with better oxygenated tumors (P =.004). In multivariate analysis, only tumor size (risk ratio [RR], 1.33; P =.0003) and evidence of pelvic nodal metastases on imaging studies (RR, 2.52; P =.0065) were predictive of PFS. However, an interaction between nodal status and oxygenation was observed (P =.006), and further analysis indicated that HP(5) was an independent predictor of outcome in patients with negative nodes on imaging (P =.007). There was a significant increase in the 3-year cumulative incidence of distant metastases in the hypoxic group (41% v 15% in those with HP(5) < 50%; P =.0023), but not in pelvic relapse (37% v 27%; P =.12). CONCLUSION: Tumor hypoxia is an independent predictor of poor PFS only in patients with node-negative cervix cancer, in addition to tumor size. Its impact appears to be related to an increased risk of distant metastases rather than to an effect on pelvic control.

Intratumoral sickling in a patient with cervix cancer and sickle trait: effect on blood flow and oxygenation.

BACKGROUND: Sickle trait affects approximately 8% of the black population in the United States and up to 40% of individuals in some parts of tropical Africa, but rarely causes clinically significant illness. This report provides the first conclusive evidence that erythrocytes in patients with sickle trait may sickle in the microvasculature of solid tumors, leading to impaired perfusion and hypoxia. CASE: A black woman who was sickle trait positive presented with stage IIIB squamous cell carcinoma of the cervix. A biopsy showed extensive intravascular sickling of erythrocytes. An aspirate of blood obtained directly from the tumor also showed numerous sickled cells. A peripheral blood smear was normal. Direct measurement of oxygen tension using the Eppendorf electrode revealed the tumor to be markedly hypoxic, with 93% of a total of 142 individual oxygen reading <5 mm Hg. CONCLUSIONS: Erythrocytes in patients with sickle trait may sickle in the microvasculature of solid tumors and contribute to reduced blood flow and the development of hypoxia. Hypoxia is a strong independent prognostic factor in patients with cervix cancer, and further study is needed to evaluate the impact of intratumoral sickling on long-term outcome.

Endometrial evaluation with transvaginal US and hysterosonography in asymptomatic postmenopausal women with breast cancer receiving tamoxifen.

PURPOSE: To determine performance characteristics of transvaginal ultrasonography (US) and hysterosonography for diagnosing endometrial abnormality in asymptomatic postmenopausal women with breast cancer receiving tamoxifen. MATERIALS AND METHODS: The authors prospectively examined 138 women receiving tamoxifen by using transvaginal US, hysterosonography, and office hysteroscopy. The combined hysteroscopic-histopathologic diagnosis was the reference standard. Sensitivity, specificity, positive and negative predictive values, and likelihood ratios of transvaginal US and hysterosonography were calculated. RESULTS: All 138 women underwent transvaginal US; 104, successful hysterosonography; and 117, successful hysteroscopy. Uterine abnormality was present in 47 (40.2%) of 117 women: 45 with polyps and two with submucosal fibroids. Receiver operating characteristic curve analysis revealed 6 mm to be the optimal endometrial thickness cutoff for diagnosing endometrial abnormalities. When a thickness greater than 6 mm or a focal endometrial finding was considered abnormal, transvaginal US had a sensitivity of 85.1% and a specificity of 55.7%. In 92 women who completed transvaginal US, hysterosonography, and hysteroscopy, hysterosonography was more specific (79.2%; P =.008) but not significantly more sensitive (89.7%; P =.508) than transvaginal US. When women with abnormal transvaginal US findings were further examined with hysterosonography, the sequential combination of transvaginal US and hysterosonography was more specific (77.1%) than transvaginal US alone (P <.001), without a significant decrease in sensitivity (78.7%; P =.25). CONCLUSION: In asymptomatic postmenopausal women receiving tamoxifen, 6 mm is the optimal endometrial thickness cutoff for diagnosing endometrial abnormalities with transvaginal US. Further examination with hysterosonography can improve specificity by reducing the high false-positive rate of transvaginal US.

Interstitial fluid pressure predicts survival in patients with cervix cancer independent of clinical prognostic factors and tumor oxygen measurements.

The purpose of this study was to determine the independent prognostic significanceof interstitial fluid pressure (IFP) measurements in cervix cancer. A total of 102 patients with newly diagnosed cervix cancer were accrued to this prospective study. There were 31 International Federation of Gynecology and Obstetrics stage IB or IIA tumors, 40 IIB tumors, and 31 IIIB tumors. The median size was 5 cm (range, 2-10 cm). Pelvic lymphadenopathy was identified radiographically in 20 patients. IFP was measured at examination under anesthesia using a wick-in-needle technique. Multiple measurements were made in each tumor. The mean IFP in individual tumors ranged from -3 to 48 mm Hg, and the median for the entire cohort was 19 mm Hg. Treatment consisted of external beam and intracavitary radiation without chemotherapy. Median follow-up was 2.5 years. The 3-year disease-free survival of all of the patients was 53%. Disease-free survival was 34% in patients with IFP >19 mm Hg, and 68% in those with lower IFP (P = 0.002). To evaluate rigorously the independent prognostic significance of IFP measurements relative to established clinical factors, a multivariate model was first developed using stepwise selection of clinical covariates. Tumor size (P = 0.0003) and pelvic lymph node status (P = 0.0016) comprised the clinical model. IFP, when added to this model, provided additional independent prognostic information (P = 0.0013). IFP was also significant (P = 0.0027) when the clinical factors and hypoxic proportion as determined with the Eppendorf electrode were analyzed together. Patients with high IFP were more likely to recur both locally and at distant sites. This study is the first to document a strong, independent prognostic importance of pretreatment IFP measurements in cervix cancer. Patients with high IFP are significantly more likely than those with low IFP to recur after radiotherapy and die of progressive disease, independent of clinical prognostic factors and the results of tumor oxygen measurements.

Results of radical radiotherapy for recurrent endometrial cancer.

OBJECTIVES: The aims of this study were to determine the overall survival (OS) and local control (LC) achieved in patients developing a locoregional recurrence of endometrial carcinoma and to define those prognostic factors that predict for improved LC and OS. METHODS: Between 1984 and 1988, 958 women were referred to Princess Margaret Hospital (PMH) with a diagnosis of endometrial carcinoma. Of these, 58 were treated for recurrent disease with radical radiotherapy (RT). Forty-two were referred with recurrence and 16 relapsed during follow-up at PMH for their primary tumor. None had received prior RT. The majority (n = 49) were treated with combined external beam RT followed by an intracavitary cesium insertion. RESULTS: The median time to relapse from original diagnosis was 1.3 years (range 0.2-13.4 years). The actuarial 5- and 10-year OS was 53 and 41%, respectively. The respective results for LC were 65 and 62%. All end-points were measured from the time of relapse. The median total dose received was 81.5 Gy. Univariate analysis showed that favorable histological features at original diagnosis (<50% myometrial involvement, grade 1-2, P = 0.007) and Perez modified staging (P = 0.02) were significant predictors for OS. The Perez staging (P = 0.02) and size of recurrence (<2 cm versus >/=2 cm, P = 0.04) were predictors for LC. CONCLUSION: Patients with localized relapse of endometrial carcinoma in whom radical radiotherapy can be administered should be treated aggressively and may be cured in over half the cases treated. Pathological findings in the original surgical specimen, size of recurrent disease, and a modified vaginal carcinoma staging system are significant predictors of local pelvic control and survival.

Interrelationship of proliferation and hypoxia in carcinoma of the cervix.

PURPOSE: In human cervix cancer treated with radiotherapy, we have previously shown from separate groups of patients that tumor hypoxia and proliferation rate as measured by bromodeoxyuridine (BrdU) labeling index (LI) are important determinants of clinical outcome. We now examine the relationship of these two pre-treatment predictive assays in 43 patients studied prospectively from 1994-98 where both tests were performed for each patient. MATERIAL AND METHODS: Newly diagnosed patients with carcinoma of the cervix were examined under anesthesia for staging purposes. Patients were given BrdU (200 mg) by intravenous route prior to the procedure. Tumor oxygenation was measured with the Eppendorf pO2 histograph. Biopsy of tumor was then performed and the BrdU LI was obtained by flow cytometry. The degree of tumor hypoxia for each tumor was expressed as median pO2 values, and as the percentage of pO2 readings <5 mm Hg (HP5). RESULTS: The median age was 53 years (range 23-79 years). There were 32 squamous, and 11 non-squamous carcinomas. FIGO stages were: IB and IIA, 8; IIB, 17; IIIB, 18; with a median tumor size of 6 cm (range 2-10 cm). The patients received uniform treatment with radical radiation therapy. There were 22 diploid and 21 aneuploid tumors. The median LI, pO2, and HP5 were 8.0%, 5.4 mm Hg, and 46.8%, respectively. Tests for linear associations showed no significant correlation between median pO2 vs. LI (r = 0.078, p = 0.62), and HP5 vs. LI (r = -0.14, p = 0.38). CONCLUSIONS: The clinical outcome in this group of patients is immature, but these results suggest that tumor hypoxia and proliferation measurements are independent and potentially complementary predictive assays in cervix carcinoma. Further investigations are required to examine the distribution of proliferating tumor cells and its relationship with hypoxic tumor cells in tissue sections with the use of immunohistological techniques and image analysis systems.

Treatment of early epithelial ovarian cancer with chemotherapy and abdominopelvic radiotherapy: results of a prospective treatment protocol.

PURPOSE: To test the hypothesis that the combination of adjuvant chemotherapy and abdominopelvic radiation (APRT) improves the outcome of patients with early ovarian cancer compared to treatment with APRT alone. METHODS AND MATERIALS: Between 1991 and 1994, 93 patients with Stage I to III, optimally cytoreduced, invasive, epithelial ovarian cancer were treated with sequential chemotherapy and APRT. Treatment was assigned using a prognostic classification that was derived from previous cohorts of patients. Low-risk patients (n = 9) received APRT alone, intermediate-risk patients (n = 66) received two courses of cisplatin followed by APRT, and high-risk patients (n = 18) received 6 courses of cisplatin and cyclophosphamide followed by APRT. RESULTS: Disease recurred in 22 patients, and was confined to the pelvis or abdomen in 15. Nine patients died and the remainder were alive with disease after receiving salvage chemotherapy. The 3-year disease-free and overall survivals were 78% and 91%, respectively. The prognostic classification used to assign treatment was the only factor that predicted disease-free survival (83% and 59% at 3 years for low/intermediate- and high-risk patients, respectively; p = 0.03). There was no detectable difference in outcome between the present series and an historical control group treated with APRT alone. Treatment was well tolerated and only 2 patients (2.5%) developed serious complications. CONCLUSION: APRT is an effective adjuvant treatment for carefully selected patients with early ovarian cancer. The addition of chemotherapy as used in this study to APRT does not significantly improve outcome compared to APRT alone.

Tumour proliferation and apoptosis in human uterine cervix carcinoma II: correlations with clinical outcome.

PURPOSE: The prognostic value of tumour proliferation and apoptosis measurements were studied prospectively in patients with carcinoma of the uterine cervix, relative to other established clinical factors. MATERIALS AND METHODS: The labelling index (LI) for bromodeoxyuridine was determined by flow cytometry (fc) and also by immunohistochemistry. Apoptosis was assessed histologically using morphological criteria. Patients were treated with radical radiation therapy (RT). RESULTS: The median/mean LI-fc were 6.7%/7.9% (range 1.52-3.9%). The median/mean apoptosis index (AI) were 1.0%/1.6% (range 0-6.8%). To date, 27 patients have died of disease, and the median follow-up for alive patients is 3.2 years (range 0.4-6.0 years). Among 64 patients who completely responded to treatment, 25 patients have relapsed (six pelvic, 17 distant and two pelvic and distant). In univariate analysis, the most significant factors for disease-free survival (DFS) were large tumour size (P=0.0001), low haemoglobin (P=0.01 ), LI-fc (DFS 67% for LI < 7%, 33% for LI > or = 7%, P=0.03), and T(pot) (DFS 66% for T(pot) > 5 days, 35% for T(pot) < or = 5 days, P=0.04) Stage, overall treatment time (OTT), S-phase fraction, ploidy, T(s), LI by histology, mitotic index, and AI were not significant. Multivariate analysis (Cox's model) showed that the only significant prognostic factors for DFS were tumour size and OTT. However, for small tumours (diameter < 6 cm), either a high LI-fc ( > or = 7%) or a high AI ( > 1%) was associated with poorer DFS, whereas patients with larger tumours (diameter > or = 6 cm) fared poorly regardless of LI-fc and AI. CONCLUSIONS: Tumour size was the most important prognostic factor in cervix carcinoma. Although none of the biologic parameters have independent prognostic significance when the effect of initial tumour size was taken into account, our data suggests that LI and AI may be useful in discriminating outcome for patients with smaller tumours when managed by radical RT. These findings support the hypothesis that rapidly proliferating tumours are less likely to be controlled with a conventional course of RT.

Oxygenation predicts radiation response and survival in patients with cervix cancer.

BACKGROUND AND PURPOSE: Hypoxia appears to be an important factor in predicting tumor relapse following radiation therapy. This study measured oxygenation prior to treatment in patients with cervix cancer using a polarographic oxygen electrode to determine if oxygenation was an important prognostic factor with regard to tumor control and survival. MATERIALS AND METHODS: Between May 1994 and June 1997, 74 eligible patients with cervix cancer were entered into an ongoing prospective study of tumor oxygenation prior to primary radiation therapy. All patients were evaluated with an Eppendorf oxygen electrode during examination under anesthesia. Oxygenation data are presented as the hypoxic proportion, defined as the percentage of pO2 readings of <5 mm Hg (abbreviated as HP5). RESULTS: The HP5 ranged from 2 to 99% with a median of 52%. With a median follow-up of 1.2 years, the disease-free survival (DFS) rate was 69% for patients with HP5 of < or =50% compared with 34% for those with HP5 of >50% (log-rank P = 0.02). Tumor size above and below the median of 5 cm was also significantly related to DFS (P = 0.0003) and patients with bulky hypoxic tumors had a significantly lower DFS (12% at 2 years) than either bulky oxygenated or non-bulky oxygenated or hypoxic tumors (65%, P = 0.0001). CONCLUSIONS: Hypoxia and tumor size are significant adverse prognostic factors in a univariate analysis of disease-free survival in patients with cervix cancer. A high risk group of patients with bulky hypoxic tumors have a significantly higher probability of relapse and death.

The role of adjuvant radiotherapy in carcinoma of the endometrium-results in 550 patients with pathologic stage I disease.

OBJECTIVES: A retrospective analysis of 550 women with pathological stage I carcinoma of the endometrium who were seen between January 1984 and December 1988 was performed in order to assess the value of adjuvant radiation therapy. METHODS: Two-hundred twenty-eight patients were treated with surgery alone (S); 97 received adjuvant external beam radiotherapy (S + EXT); 217 received external beam radiotherapy and colpostats (S + EXT + IC); and 8 patients received only colpostats (S + IC). Pelvic radiation therapy, usually 40 Gy in 20 fractions, was administered to 94% of patients whose tumors showed greater than 50% myometrial invasion and to 89% of patients with FIGO grade 3 tumors. Colpostats were used in 40% of patients, the majority of whom had lower uterine segment involvement. RESULTS: The overall survival rate for the whole group using Kaplan-Meier estimates was 84% at 5 years. The 5-year overall survival rates for each treatment group, excluding the S + IC group, were 90% for S alone, 79% for S + EXT, and 82% for S + EXT + IC. The 5-year disease-free survival rates were 84, 77, and 77%, respectively. Local control rates at 5 years were 93, 94, and 95% in the three treatment groups, but the patterns of relapse were different. Distant metastases occurred more frequently among the patients who received adjuvant radiation therapy (36/49, 73%) than among those who did not (4/19, 21%). Late toxicity was documented in 66 patients. Twelve patients had EORTC/RTOG grade 3 and 4 complications; all had been treated with S + EXT + IC. FIGO grade (P = 0.009), lower uterine segment involvement (P = 0.009), and age (P = 0.03) were significant predictors of worse disease-free survival in a multiple regression analysis. CONCLUSIONS: The addition of vaginal vault brachytherapy to external beam radiotherapy did not appear to improve local cure rates nor survival, but increased the incidence of late radiation toxicity.

Effect of filgrastim (G-CSF) during chemotherapy and abdomino-pelvic radiation therapy in patients with ovarian carcinoma.

PURPOSE: To evaluate the safety and effectiveness of filgrastim (granulocyte colony-stimulating factor, G-CSF) in reducing neutropenia and treatment interruptions during whole abdominal radiotherapy for ovarian cancer. METHODS AND MATERIALS: Sixteen patients with ovarian cancer treated with 2 to 6 courses of cisplatin-containing chemotherapy and abdomino-pelvic radiation therapy received filgrastim for neutrophil counts <2 x 10(9)/L. Endpoints for analysis included the ability to maintain the neutrophil count in the target range, number of treatment interruptions due to neutropenia, and toxicity attributed to filgrastim. RESULTS: Fourteen patients received a mean of 2.9 courses of filgrastim (each with a mean duration of 4.1 days), with no treatment interruptions due to neutropenia. The majority of neutrophil counts were maintained above the target range of 2 x 10(9)/L during treatment. Thrombocytopenia requiring treatment interruption was seen in six patients and necessitated platelet transfusions in one. Thrombocytopenia occurred at a mean abdominal radiation dose of 2207 cGy and in all but one patient was preceded by one or more episodes of neutropenia. In comparison with a control group of 31 patients treated without filgrastim there was no reduction in treatment interruptions. Four patients did not complete treatment because of persistent thrombocytopenia yet received a mean of 94% of the planned abdominal radiation dose and 69% of the planned pelvic dose. Filgrastim toxicity was limited to mild skeletal pains in six patients and a Grade 1 skin rash in two patients. CONCLUSIONS: Filgrastim is safe and effective in preventing neutropenia and reducing neutropenic treatment interruptions during abdominal radiotherapy in patients with ovarian cancer. However, there was no clear benefit to the use of filgrastim as thrombocytopenia became the dose-limiting toxicity resulting in a risk of treatment interruptions and early termination of radiotherapy.

Interstitial fluid pressure in cervical carcinoma: within tumor heterogeneity, and relation to oxygen tension.

BACKGROUND: Interstitial fluid pressure (IFP) is elevated in many animal and human tumors. The authors assessed tumor IFP and its relation to tumor oxygenation in a prospective clinical study of patients with cervical carcinoma. METHODS: Measurements were made in 77 patients with cervical carcinoma prior to treatment. IFP was measured in normal paravaginal submucosal tissue and at one to five positions in the visible tumor with the patients anesthetized and in the lithotomy position. Tumor oxygen tension was measured immediately prior to IFP using a polarographic needle electrode. Patients were treated with radiotherapy only. Response was evaluated 3 months after the completion of radiotherapy. RESULTS: There was substantial variation in IFP from region to region in some tumors. The mean IFP in individual tumors ranged from 3 to 48 millimeters of mercury (mmHg). The overall mean and median values for the entire patient group were 19 mmHg and 17 mmHg, respectively. IFP was significantly higher in tumor tissue than in normal tissue (P < 0.0001). Tumors with high IFP were more likely to be hypoxic (P < 0.007) and less likely to regress completely with radiotherapy (P < 0.04). CONCLUSIONS: IFP in cervical carcinoma is elevated above normal tissue values. Multiple measurements are needed to evaluate IFP in these tumors. High IFP is associated with hypoxia and may provide information about the mechanism of hypoxia on which treatment can be based.

Squamous cell carcinoma of the breast.

OBJECTIVE: To review the mammographic and ultrasonographic features of primary breast cancer containing squamous cell carcinoma. PATIENTS AND METHODS: From medical records for breast cancer patients seen over a 37-year period the authors identified 19 patients with squamous cell carcinoma, for 5 of whom histologic sections and imaging studies were available. The tumours were classified on the basis of histologic findings as pure (in two patients) or predominantly (in three patients) squamous cell carcinoma. Mammograms were available for four of the patients, and the mammographic report only was available for analysis for the fifth. Ultrasonography had been performed for four of the patients; the images were available for two of the patients and the reports only for two. RESULTS: The median age of the patients was 55 years. The mean size of the tumours, all of which were palpable, was 5.0 cm. None of the tumours was connected to the skin, arose in the nipple-areolar complex or was metastatic. On mammography, the margins of all five masses, which were oval in shape, were indistinct and partly well-circumscribed; in three cases, the tumour margin was also partly spiculated. No malignant microcalcifications were seen. The two "pure" squamous cell carcinoma tumours appeared on ultrasonography as solid hypoechoic masses, and two of the predominantly squamous cell carcinoma tumours had both cystic and solid components. At gross pathological examination, four of the tumours (two "pure" and two predominantly squamous cell carcinoma) were cystic, which reflected areas of necrosis and cyst formation. CONCLUSION: Although "pure" or predominantly squamous cell carcinoma is a rare histologic variant of breast cancer that lacks any typical mammographic features, this tumour can be added to the differential diagnosis of cystic breast masses seen on ultrasonography.

Proliferation measurements with flow cytometry Tpot in cancer of the uterine cervix: correlation between two laboratories and preliminary clinical results.

PURPOSE: To assess the prognostic value of the pretreatment potential doubling time (Tpot) in carcinoma of the uterine cervix, relative to other established clinical factors. METHODS AND MATERIALS: Fifty-two patients with cervical cancer were studied prospectively from March 1991 to October 1993. Pretreatment evaluation included examination under anesthesia and tumor biopsy 6 h following the intravenous administration of bromodeoxyuridine (200 mg). Tpot was determined by deriving the labeling index (LI) and S-phase synthesis time (Ts) using flow cytometry. Six patients were not evaluable and excluded. The remaining 46 patients (average age 55 years) were treated uniformly with radical radiation therapy. There were 39 squamous carcinomas and 7 adenocarcinomas. Fédération Internationale de Gynécologie et d'Obstétrique (FIGO) stages were: Ib and IIa, 12 patients; IIb, 18 patients; III and IV, 16 patients. The median external beam dose was 50 Gy (range, 45-52.8 Gy) delivered in 25 fractions. The median intracavitary dose was 40 Gy (range. 25.5-40 Gy) delivered with a single line source to a point 2 cm lateral of the midline, with a mean dose rate of 0.71 Gy/h. The median overall treatment time was 45 days (range, 34-73 days). As of July 31, 1994, 12 patients had died of disease, and the average follow-up for alive patients was 1.4 years (range, 0.5-3.3 years). RESULTS: There were 27 tumors with diploid deoxyribonucleic acid (DNA) content and 19 tumors were aneuploid. The median and mean Tpot for the 46 patients were 5.5 and 6.6 days, respectively [range, 2.0-25.6 days; coefficient of variation (CV), 74%]. For 25 patients where Tpot measurements were performed at two separate laboratories, there was a fair correlation (r = 0.74), but systematic differences were detected suggesting that the lack of agreement was not simply due to intratumoral variation. To date, 30 patients remained disease free, while 8 patients had pelvic failure and 9 patients developed distant metastases as the first failure site (1 patient developed both at the same time). In univariate analysis, the only significant prognostic factor for disease-free survival was tumor size (p = 0.004). A short Tpot (or high LI) and long overall treatment time (OTT) were weakly associated with poorer disease-free survival, although not statistically significant (1/Tpot, p = 0.14; LI, p = 0.23; OTT, p = 0.04). Age, FIGO stage, hemoglobin level, S-phase fraction, DNA ploidy, and Ts were not associated with disease-free survival. Multiple regression analysis was not performed because of the relatively small number of patients and short follow-up. CONCLUSIONS: Tpot values determined with current techniques by different laboratories cannot be used interchangeably for the purpose of therapy decisions. Vigorous quality assurance and standardization of the laboratory procedures and analysis methods are important to reduce interlaboratory variation. In this uniformly treated group of patients with cancer of the uterine cervix, traditional clinical prognostic factors remain the most important. Preliminary data suggest that the flow cytometry-determined Tpot and labeling index predict for disease-free survival, although a larger number of patients with longer follow-up is required to assess the true prognostic significance of these assays and to determine if their effect is independent of other clinical factors.

Prognostic factors in patients with cervix cancer treated by radiation therapy: results of a multiple regression analysis.

A retrospective analysis of 965 patients with invasive cervix cancer treated by radiation therapy between 1976 and 1981 was performed in order to evaluate prognostic factors for disease-free survival (DFS) and pelvic control. FIGO stage was the most powerful prognostic factor followed by radiation dose and treatment duration (P values = 0.0001). If the analysis was limited to patients treated with radical doses of 75 Gy or more, dose was no longer significant. Young age at diagnosis, non-squamous histology and transfusion during treatment were also adverse prognostic factors for survival and control. Para-aortic nodal involvement on lymphogram was associated with a reduction in DFS (P = 0.0027), whereas pelvic lymph node involvement alone was not. In patients with Stage I and IIA disease, tumour size was the most powerful prognostic factor for survival (P = 0.0001) and the extent of pelvic sidewall involvement was significant in patients with Stage III tumours (P = 0.007). Histological grade appeared to be a predictive factor but was only recorded in 712 patients. These features should be considered in the staging of patients and in the design of clinical trials.

Carcinoma of the vagina--experience at the Princess Margaret Hospital (1974-1989).

The charts of 153 patients with vaginal carcinoma or carcinoma in situ seen at Princess Margaret Hospital between 1974 and 1989 were analyzed with respect to treatment modality, radiation dose and technique, complications, and survival. One hundred and twenty-eight patients were treated with radiation therapy, of which 10 received radiation postoperatively and 26 concomitant chemotherapy. The overall 5-year actuarial cause-specific survival was 66%. The 5-year cause-specific survivals by stage were Stage 0 (C-I-S) 100%, Stages I/II 77%, and Stages III/IV 56%. Late complications from treatment were infrequent and in only 12 patients were such complications classified as severe. Univariate analysis indicated that size and stage of tumor, histological grade, patient age, and radiation dose > 7000 cGy were significant factors in predicting survival, although in a multivariate analysis only size and stage retained significance. Fifty-one patients had a prior gynecological malignancy arising 1-37 years previously, of which 34 had cervical cancers. Radiotherapy is an effective treatment for all stages of carcinoma of the vagina and doses of at least 7000 cGy are recommended to maximize tumor control.

Phylloides tumor of the breast: a report of 14 cases.

The objective of this retrospective study is to determine the role of radiation therapy in the management of benign phylloides tumors. Fourteen patients with a diagnosis of benign phylloides tumor (PT) and registered at the Princess Margaret Hospital are included in the study. Definitive surgery consisted of either lumpectomy in seven patients or mastectomy in the other seven patients. One patient died of her disease, and the remaining patients had no evidence of disease at last follow-up (median 38.4 months). Among these 13 patients, 4 had at least one recurrence and the recurrence rate was higher for the group who underwent lumpectomy (43% compared with 28%). One patient was treated by lumpectomy and adjuvant radiation therapy, and had no subsequent recurrence (follow-up time 35.5 months). The role for radiation therapy in the management of this disease remains unclear.