Medullary thyroid carcinoma: multivariate analysis of prognostic factors influencing survival

Background Medullary thyroid carcinoma (MTC) is a rare development of thyroid cancer with a no negligible mortality rate. Our aim was to determine factors that predict outcome in patients with MTC. Methods We reviewed the records of all patients with MTC (n=56) who underwent treatment at our institution between January 1990 and December 2000. Univariate and multivariate analysis of clinicopathologic predictors of MTC outcome were performed to identify subsets of patients with different probabilities in terms of overall survival, local recurrence, and distant metastases. Results Multivariate analysis demonstrated that a statistically significant decrease in overall survival is associated with T4b tumours (p=0.06), the presence of distant metastases at the time of presentation (p=0.033), lymphatic invasion (p=0.099), and postoperative treatment (p=0.045). Conclusions The analysis of survival curves of patients with MTC shows that the occurrence of locoregional and distant metastases occurs preferentially within the first 5 years, which identifies this as a crucial period for follow-up. In this series of patients with MTC, the tumours classified as T4b, metastases at presentation, the presence of lymphovascular invasion, and postoperative treatment were the most important prognostic features. At present, there is no available beneficial adjuvant therapy. However, as the development of molecular therapy progresses, it should be tested in clinical trials with the purpose of achievement of novel targeted therapies for selected MTC patients with risk factors.     

Long-term results of radical surgery for rectal cancer: multivariate analysis of prognostic factors influencing survival and local recurrence.

AIMS: To evaluate consistent radical surgery performed over a 13-year period for rectal cancer in terms of local tumour control and long-term survival. METHODS: Radical surgical procedure principally using total mesorectal excision (TME) for middle and lower rectal tumours, high ligation of the inferior mesenteric artery and sphincter-saving resections (SSR) whenever possible, has been performed prospectively since January 1984. RESULTS: Tumour resection was possible in 98.8% (636/644), potentially curative resections (UICC/AJCC R0 resection) in 85.7% (552/644) and sphincter preservation in 71.7% (462/644). Five- and 10-year observed survival rates, surgical mortality not excluded, for all patients were 49.2% and 37.4%. Tumour-adjusted 5- and 10-year survival rates were 60.5% and 55.3%. For curatively operated patients (UICC/AJCC R0) 5- and 10-year observed survival rates were 56.3% and 42.6% and tumour-adjusted survival rates were 68.6% and 62.7%. The 5- and 10-year local recurrence rates for R0 resected patients were 12.0% and 12.6%. Post-operative hospital mortality was 3.1%. CONCLUSIONS: Multivariate analysis using Cox's model identified increasing pT category and pN category, old age and low tumour location as detrimental factors having independent influence on survival. For local tumour failure only pT and pN category as well as adjuvant radiation therapy were identified in the Cox model as having an independent detrimental influence.     

Pancreatic neuroendocrine tumor: A multivariate analysis of factors influencing survival

Background

The outcomes of pancreatic neuroendocrine tumors are extremely diverse, and determining the best strategy, optimal timing of therapy and the therapeutic results depend on understanding prognostic factors. We determined the clinical, radiological and histological factors associated with survival and tumor recurrence for patients with pancreatic neuroendocrine tumor.

Methods

From January 1, 1991 to December 31, 2011, 127 patients with pancreatic neuroendocrine tumor underwent pancreatectomy. The variables including clinical characteristics, surgical data and pathological findings were examined by univariate and multivariate analyses.

Results

There were 103 patients with non-functional tumors (81%). Sixty-four patients (50%) underwent left pancreatectomy, 51 (42%) patients underwent pancreatico-duodenectomy, 12 (9%) patients underwent enucleation and 2 patients (1%) underwent central pancreatectomy. Forty-eight patients (38%) had synchronous liver metastases. Six patients (5%) required portal vein resection, and 19 (15%) patients required enlarged “en-bloc” resection of adjacent organs. The overall morbidity and mortality rates were 48% and 2.3%, respectively. The 1-, 3- and 5-year overall survival rates were 94%, 84%, and 74%, respectively. In multivariate analyses, synchronous liver metastases (p = 0.02) and portal vein resection (p < 0.01) were independent prognostic factors of survival.

Conclusions

Synchronous liver metastases and portal vein resection were found to be independent factors influencing survival.     

Prostatic carcinoma: a multivariate analysis of prognostic factors.

Tissue specimens from 150 patients with localised prostatic carcinomas and 116 patients with prostatic carcinomas with distant metastases were analysed for histological grade (WHO and Gleason) and immunoreactivity for prostate acid phosphatase (PAP), prostate-specific antigen (PSA), neurone-specific enolase (NSE), p53 protein, c-erbB-2 protein, cytokeratins (AE1/AE3) and vimentin. After stratification for the presence or absence of distant metastases, multivariate regression analysis revealed that WHO grading was the most powerful independent prognosticator, followed by age and prostate acid phosphatase expression. There was a trend towards reduced survival with decreasing prostate-specific antigen reactivity. The Gleason system showed poor prognostic ability. The analysis predicted reduced survival in the presence of extensive neurone-specific enolase reactivity, mostly because of one case of small-cell carcinoma.     

The natural history of gastric cancer and prognostic factors influencing survival

This study of 783 patients with histologically confirmed gastric carcinoma has confirmed the importance of several previously recognized patient- and tumor-related characteristics related to prognosis and identified some new ones. Of the tumor-related factors, the ones that showed the strongest relationship to survival following curative gastric resection were tumor stage, histologic type, breach of lymph-node capsule, sinus histiocytosis, and gross appearance. Of the tumor- and patient-related factors, the ones that showed the strongest relationship to survival from time of diagnosis of surgically noncurable disease were status of primary, liver metastasis, serum bilirubin level, ascites, extent of tumor burden, and weight loss. The effect of treatment with 5-fluorouracil (5-FU) on survival duration was at best only minimal. Only those patients who received two or more cycles of 5-FU therapy had survival advantage over the remaining patients. The use of regression analysis has made it possible to make predictions of the prognosis of the patients. These predictions could be used in future studies to determine comparability of prognosis of various groups included in different studies and different arms of a randomized study.     

Inflammatory breast cancer. Determination of prognostic factors by univariate and multivariate analysis

Between January 1977 and June 1983, 64 consecutive patients were treated for unilateral inflammatory nonmetastatic breast cancer. Our protocol included three or four courses of induction chemotherapy, then locoregional irradiation therapy with Co-60, followed by maintenance chemotherapy only if induction chemotherapy had proven effective. Eight patients with a residual tumor after radiotherapy underwent a modified radical mastectomy. Actuarial 3-year overall survival for the whole group was 38%, and the median disease-free survival time was 19 months. The effect of 17 factors on overall survival or disease-free survival was analyzed. With univariate analysis, eight factors were found to affect overall survival or disease-free survival: extent of initial erythema, size of initial edema, lymph node involvement, erythema present at the end of initial chemotherapy, erythema present at the end of radiotherapy, tumor size at the end of induction chemotherapy, residual breast tumor at the end of maintenance chemotherapy, and performance of a radical mastectomy. Age at diagnosis, menopausal status, type of chemotherapy, and date of appearance of inflammatory signs did not influence prognosis. Multivariate analysis using the Cox proportional hazard model isolated three bad prognosis factors: erythema involving the whole breast at initial diagnosis, erythema present at the end of initial chemotherapy, and lymph node involvement.     

Medullary thyroid cancer

Opinion statement Patients with clinically evident medullary thyroid cancer should have a total extracapsular thyroidectomy with bilateral central neck dissection and an ipsilateral prophylactic or therapeutic modified (functional) radical neck dissection when the primary tumor is greater than 1 cm and when the central neck nodes are positive. A prophylactic contralateral neck dissection should be done when the primary tumor is bilateral and when there is extensive lymphadenopathy on the side of the primary tumor. Patients who have gross, unresectable residual medullary thyroid cancer should receive postoperative external radiotherapy. Patients who are carriers of germ-line RET proto-oncogene point mutations or have an elevated (basal or stimulated) calcitonin levels on screening should have a prophylactic total thyroidectomy before age 6 years. In patients with an elevated basal or stimulated plasma calcitonin level and an intrathyroidal nodule on ultrasound, a total thyroidectomy and central neck lymph node dissection should be done. Patients with persistent or recurrent medullary thyroid cancer should have a complete thyroidectomy (if not done initially) and bilateral central and modified radical neck dissection, including upper mediastinal lymphadenectomy. Patients who are symptomatic from distant medullary thyroid cancer metastases (diarrhea, flushing, weight loss, or bone pain) should be treated with somatostatin analogs. Bone metastases should be resected if possible, and symptomatic lesions that are unresectable should be treated with external radiotherapy. Cytoreductive procedures such as radiofrequency ablation or cryoablation for liver metastases should be considered in symptomatic patients to reduce tumor burden. Localized pulmonary metastases should be resected. Chemotherapy or radioactive immunotherapy (iodine 131 labeled carcinoembryonic antigen monoclonal antibody) protocols should be considered in patients with nonoperative widely metastatic progressing medullary thyroid cancer.     

Medullary thyroid cancer

The goal in managing patients who have MTC is to detect and surgically remove disease at an early stage. Tumor marker-based biochemical screening and DNA-based genetic screening have created the opportunity for effective prophylactic surgery in patients at risk for hereditary MTC. Complete surgical resection is critical for cure because cervical reoperation for persistent or recurrent disease benefits only select patients. With the advent of therapies that target the RET-activated pathways, new hope may be emerging for patients who have locally advanced or metastatic disease.     

Survival and prognostic factors in differentiated thyroid cancer--a multivariate analysis of 1,055 cases

Survival (5- and 10-year) and prognostic factors of all differentiated thyroid cancer patients (n = 1,055) occurring in Norway in 1970-79 are presented. The multivariate analysis (GLIM) revealed that stage and age were the only significant prognostic factors. Sex and histological type could not be proved to be of major prognostic value. The decline in relative survival with age was different in the three stages, appearing as a continuous decrease in stage 3, while in stage 1 the decrease was present only in patients older than 75 years.     

Radiotherapy in T1 laryngeal cancer: prognostic factors for locoregional control and survival, uni- and multivariate analysis

From 1975 through 1985, 194 patients with T1 glottic, 37 patients with T1 supraglottic, and 3 patients with T1 subglottic cancer were treated with radiotherapy. Local control and ultimate locoregional control (after salvage surgery) was 91% and 97% for T1 glottic, 84% and 81% for T1 supraglottic, and 2/3 and 3/3, respectively for subglottic tumors. In uni- and multivariate analysis local control for glottic tumors was associated with extension of the tumor on the vocal cord (entire length of vocal cord vs others, p = 0.01) and continuation of smoking after therapy (yes/no, p = 0.03). No prognostic factor for local control was found in supraglottic tumors. However, regional control and survival were impaired by N stage (N0 vs N+, p less than 0.0005), local recurrence (yes/no, p less than 0.0005), and extension of the tumor (one supraglottic subsite vs more than one, p less than 0.05). Mild late complications were seen in 13% of patients without salvage therapy. Following univariate analysis, field size, fraction size (greater than 2 Gy), maximum tumor dose (greater than 70 Gy), age, post-treatment biopsy, and tumor site were associated with complication rate. Following multivariate analysis, site, fraction size, maximum tumor dose, and continuation of smoking after therapy were independent prognostic factors for mild late complications (mostly arytenoid edema).     

Recurrent breast cancer: factors influencing survival, including treatment.

Factors influencing survival were reviewed in 464 patients with recurrent breast cancer. Site of first recurrence and rate of tumor progression governed prognosis more than choice of initial therapy. Overall median survival was 22--26 months for bone/soft-tissue disease, 10--12 months for pleura/lung, and 4--6 months for liver/brain recurrence. Patients with slow rates of tumor progression at each site had longer survival terms than did rapid progressors. About 50% of patients with bone or soft-tissue recurrence had slow progression and long survival, regardless of whether initial treatment was local or systemic. In visceral recurrence, the number of patients with slow progression was doubled with systemic therapy in comparison to local treatment (from 16--20% for the latter to 37--38% for the former). In addition, long-term survival in patients with similar progression rates was best using initial systemic therapy.     

Basosquamous carcinoma: analysis of prognostic factors influencing recurrence

BACKGROUND: Basosquamous carcinoma is a rare malignancy, with features of both basal cell carcinoma and squamous cell carcinoma. Some authors believe that basosquamous carcinoma merely is a variant of basal cell carcinoma, whereas others have suggested that basosquamous carcinoma may behave more aggressively. To the authors' knowledge the largest published series to date, comprised of 35 cases, was reported >20 years ago. The authors reviewed their recent experience with basosquamous carcinoma to identify prognostic factors influencing recurrence. METHODS: The medical records of all patients with the diagnosis of basosquamous carcinoma treated at the University of Louisville-affiliated hospitals between 1985-1988 were reviewed by a senior pathologist. Prognostic factors were analyzed using Cox regression analysis and the log rank test. RESULTS: Thirty-one cases of basosquamous carcinoma were identified in 28 patients. The median age at diagnosis was 68 years (range, 10-94 years). The median follow-up was 60 months (range, 12-312 months). Seventy-five percent of cases were located on the face, neck, and scalp. One patient had regional lymph node metastasis synchronous with the primary tumor. Patterns of recurrence were: local recurrence only (five patients), local recurrence plus regional lymph nodes (three patients), and pulmonary plus regional lymph nodes (one patient). One patient died of pulmonary metastasis. Significant factors predictive of recurrence (P<0.01) were male gender, positive surgical resection margin, lymphatic invasion, and perineural invasion. Although tumor size was not a statistically significant factor overall (P = 0.076), the 3 patients with lymph node metastases had large tumors (measuring 2 cm, 5 cm, and 5 cm, respectively). CONCLUSIONS: Basosquamous carcinoma is an aggressive epithelial neoplasm with a propensity for local recurrence and potential for distant metastatic spread. This behavior differs substantially from basal cell carcinoma. Complete resection with negative surgical margins is essential. Long term follow-up for the detection of local recurrence and distant metastatic spread is recommended.     

Medullary cancer of the thyroid

Medullary thyroid cancer (MTC) is either of the sporadic or familial type, whether it be isolated or constitute part of a type II multiple endocrine neoplasia. Progress in the knowledge of the disease has recently been obtained in the following ways: the IRMA assay of mature calcitonin, the disease marker, has permitted earlier diagnosis of familial cases and recurrence; the locus assignment of the gene on chromosome 10 now enables a valid discrimination in certain families of gene carriers; collaborative clinical, biological, pathological, therapeutic and epidemiological research on a nation-wide scale has had a beneficial effect on patients, with improvement in diagnosis of the familial forms, in disease prognosis, in cancer detection at an infraclinical stage, and in the regrouping and distribution of families in France.     

Spinal metastases from thyroid cancer: Some prognostic factors

BackgroundSpinal metastases (SpMs) from thyroid cancers (TC) significantly reduce quality of life by causing pain, neurological deficits in addition to increasing mortality. Moreover, prognosis factors including surgery remain debated.MethodsData were stored in a prospective French national multicenter database of patients treated for SpM between January 2014 and 2017. Fifty-one consecutive patients affected by TC with 173 secondary SpM were included.ResultsMean overall survival (OS) time for all patients from the diagnosis of a thyroid SpM event was 9.1 years (SD 8.7 months). The 1-year, 5-year and 10-year survival estimates were 94% (SD 3.3), 83.8.0% (SD 5.2), and 74.5% (SD 9.9). The median period of time between primary thyroid tumor diagnosis and the SpM event was 31.4 months (SD 71.6). In univariate analysis, good ECOG-PS (status 0 and 1) (p < 0.0001), ambulatory status (Frankel score) (p < 0.0001) and no epidural involvement (p = 0.01), were associated with longer survival, whereas cancer subtype (p = 0.436) and spine surgery showed no association (p = 0.937). Cox multivariate proportional hazard model only identified good ECOG-PS: 0 [HR: 0.3, 95% CI 0.1–0.941; p < 0.0001], 1 [HR: 0.8, 95% CI 0.04–2.124; p = 0.001] and ambulatory neurological status: Frankel E [HR: 0.262, 95% CI 0.048–1.443; p = 0.02] to be independent predictors of better survival.ConclusionFor cases presenting SpM from TC, we highlighted that the only prognostic factors were the progression of the cancer (ECOG-PS) and the clinical neurological impact of the SpM (Frankel status). Surgery should be discussed mainly for stabilization and neurological decompression.     

842例大肠癌生存状况及其影响因素的多因素分析

目的　研究我国大肠癌生存情况及其影响因素 ,以帮助判断预后。方法　对 1980～ 1999年于浙江大学医学院附属第二医院同一研究小组作大肠癌根治手术并经临床病理证实的 84 2例大肠癌 ,用 SPSS软件对 36个临床病理因素进行了单因素 Kaplan- meier生存分析和多因素 Cox比例风险模型分析。结果　 84 2例大肠癌 5、10和15年生存率分别为 6 6 .3%、5 4 .2 %和 4 8.5 % ,Cox多因素分析结果显示 ,肠梗阻、慢性便秘史、家族肿瘤史、肿瘤部位、Dukes'分期是大肠癌预后的影响因素。其中 ,无肠梗阻史患者的 5和 10年生存率 (6 7.9%和 5 5 .8% )比有肠梗阻史的患者 (5 5 .3%和 4 4 .4 % )高 11%～ 12 % ,无慢性便秘史的 (6 6 .9%和 5 5 .2 % )比有慢性便秘史的 (5 5 .1%和37.9% )高 12 %～ 17% ,有家族肿瘤史的 (78.5 %和 6 9.8% )比无家族肿瘤史的 (6 3.4 %和 5 0 .7% )高 15 %～ 19% ,结肠癌患者的 5和 10年生存率 (78.3%和 6 7.7% )要高于直肠癌患者 (5 8.2 %和 4 5 .6 % ) 2 0 %～ 2 2 %。在 Dukes'分期中 ,A期的生存率最高 ,5和 10年生存率达 83.8%和 73.5 % ,B期为 74 .9%和 6 4 .9% ,C期为 5 0 .9%和 36 .4 % ,D期 (有邻近器官转移但仍能作根治手术者 )最低 ,为 4 7.9%和 32 .2 %。上述各因素的生存曲线比较     

Medullary thyroid carcinoma: Prognostic factors and treatment

Seventy-five patients with medullary thyroid carcinoma (MTC) have been treated at Institut Gustave-Roussy from 1932 to 1979. Of these, 13 patients had distant metastases and received palliative treatment, their median survival was 3 years. Sixty-two patients with WC limited to the neck received curative treatment: 6 had exclusive external radiotherapy for inoperable disease and 56 were surgically treated: 23 by total thyroidectomy and 33 by partial thyroidectomy. After surgery 29 patients received external radiotherapy for cervical lymph node involvement ($\text{25}\text{29}$) and/or incomplete surgical resection ($\text{12}\text{27}$). The survival rate was 69% at 5 years and 48% at 10 years. It was lower in patients with distant metastases at presentation (p < 10^?5), with tumoral infiltration of the posterior tissue planes (p < 0.025) and in patients in whom surgical excision bad not been satisfactory (p < 0.01). It was not correlated with cervical lymph node involvement probably because those patients with lymph node involvement had been irradiated. The 29 patients who received post-operative cervical radiotherapy had initially more extensive local disease (p < 0.05) than the 27 patients treated by surgery alone, nevertheless their survival was slightly higher. No difference in survival rate was observed between patients treated by total thyroidectomy or partial thyroidectomy, among whom only 4 local recurrences occurred. Three of the 6 patients treated with external radiotherapy alone experienced long survival (4, 7 and 10 years) and a fourth is still in clinical remission 4 years after treatment. The effectiveness of chemotherapy in patients with metastases was poor, only one patient out of 6 had a partial remission following a treatment by adriamycin. In the familial form and multiple endocrine neoplasia type II, total thyroidectomy appears to be indicated. In the sporadic cases, partial thyroidectomy is usually sufficient. External radiotherapy is effective in MTC and seem to be able to eradicate small foci of residual tumor; it is indicated when surgical excision is impossible or Incomplete.     

Clinical stage I and II endometrial carcinoma: multivariate analysis of prognostic factors.

In 221 patients with FIGO stage I and II endometrial carcinoma, the impact on survival of age at diagnosis, menopausal status, FIGO stage, myometrial invasion, tumor grade and histology was evaluated by univariate and multivariate analysis. At a median follow-up of 50 months (range 45-210), 42 patients had died, and therefore overall survival was 81% (179/221). Univariate analysis showed that age, menopausal status and histology did not influence survival, whereas FIGO stage, myometrial invasion and tumor grade were important prognostic factors. Multivariate analysis showed that tumor grade had a significant and independent impact on survival and confirmed that FIGO stage is the most important parameter influencing survival.     

CA 125 half-life in ovarian cancer: a multivariate survival analysis.

Serum CA 125 regression after cytoreductive surgery and during the first three courses of chemotherapy was studied in 60 ovarian cancer patients and compared to known prognostic factors. Various methods reported in the literature to calculate a CA 125 half-live value were compared. Using two exponential regression models (Van der Burg et al., 1988; Buller et al., 1991), mean half-lives in stage I-II patients after complete cytoreductive surgery were respectively 10.7 days (range: 5-23) and 9.8 days (range: 7-15). Within stage III-IV patients, a significant positive correlation was seen between survival and (a) stage III (P = 0.002), (b) residual tumour < or = 1 cm (P = 0.02), (c) CA 125 normalisation after three courses (P = 0.003) and (d) CA 125 half-life < or = 20 days (P = 0.02-0.004, depending on the method used for half-life calculation). The median survival times of patients with and without a CA 125 normalisation after three courses were 27 and 14 months respectively (P = 0.003). When using the model of Buller et al. patients with a CA 125 half-life < or = 20 days had a median survival of 28 months compared to a median survival of 19 months for patients with CA 125 half-lives > 20 days (P = 0.004). Half-life calculations only showed a significant correlation with survival, if pre-surgery CA 125 levels were used as a baseline. In a survival analysis using the Cox proportional hazards model, stage of disease was the most predictive variable for survival (P = 0.006). The only additional independent prognostic factor for survival was the CA 125 half-life calculated according to Buller [derived from the formula: CA 125 = exp. [i-s x (days after surgery)], in which i is the y-axis intercept and s is the slope of the CA 125 regression curve]. A CA 125 half-life < or = 20 days vs > 20 days calculated using this formula, provides an independent prognostic factor for survival in stage III-IV patients early in the course of therapy (P = 0.04).