Comparison between intravesical and oral administration of 5-aminolevulinic acid in the clinical benefit of photodynamic diagnosis for nonmuscle invasive bladder cancer

BACKGROUND:

This study was undertaken to evaluate the clinical value of photodynamic diagnosis (PDD) with intravesical and oral instillation of 5‐aminolevulinic acid (ALA) (ALA‐PDD), and transurethral resection of bladder tumor (TURBT) guided by ALA‐PDD (PDD‐TURBT) for nonmuscle invasive bladder cancer.

METHODS:

Of all 210 cases, 75 underwent PDD with intravesically applied ALA, and 135 cases underwent PDD with orally applied ALA. Diagnostic accuracy was evaluated by comparing the level on images of ALA‐induced fluorescence with the pathological result. PDD‐TURBT was performed in 99 completely resectable cases corresponding to 210 ALA‐PDD cases. To evaluate the abilities of PDD‐TURBT, survival analysis regarding intravesical recurrence was retrospectively compared with the historical control cases that underwent conventional TURBT.

RESULTS:

The diagnostic accuracy and capability of ALA‐PDD were significantly superior to those of conventional endoscopic examination. Moreover, 72.1% of flat lesions, including dysplasia and carcinoma in situ, could be detected only by ALA‐PDD. The recurrence‐free survival rate in the cases that underwent PDD‐TURBT was significantly higher than that of conventional TURBT. Moreover, multivariate analysis revealed that the only independent factor contributing to improving prognosis was PDD‐TURBT (hazard ratio, 0.578; P = .012). Regardless of the ALA administration route, there was no significant difference in diagnostic accuracy, ability of PDD, or recurrence‐free survival. All procedures were well tolerated by all patients without any severe adverse events.

CONCLUSIONS:

This multicenter study is likely to be biased, because it is limited by the retrospective analysis. This study suggests that regardless of the ALA administration route, ALA‐PDD and PDD‐TURBT are remarkably helpful in detection and intraoperative navigation programs. Cancer 2012;. © 2011 American Cancer Society.     

Intracranial hemangiopericytoma: clinical experience and treatment considerations in a modern series of 40 adult patients

INTRODUCTION:

Intracranial hemangiopericytoma (HPC) is a malignant meningothelial tumor. Because of its rarity, few guidelines exist for optimal management.

METHODS:

University of California at San Francisco patients managed for intracranial HPC were compiled into a single database based on a retrospective review of patient records. Univariate and multivariate regression was performed to determine factors that independently predicted treatment outcomes.

RESULTS:

A total of 40 patients with intracranial HPC were treated from 1989 to 2010. Treatment and follow‐up information was available for analysis on 35 patients. The median survival for all patients was 16.2 years after date of diagnosis, with 1‐year, 5‐year, and 10‐year survival rates of 100%, 92%, and 68%, respectively. Nineteen patients (54%) had HPC recurrence. The median time until recurrence was 5 years, with 1‐year, 5‐year, and 10‐year progression‐free survival rates of 96%, 49%, and 28%, respectively. Seven patients (20%) developed extracranial metastasis. Tumor characteristics associated with earlier recurrence included size ≥6 cm (log‐rank, P < .05) and nonskull base location (log‐rank, P < .05). Strategies combining adjuvant radiation with tumor resection appeared to hinder tumor progression, but had no effect on overall survival or the development of metastasis. Greater extent of resection was associated with increased overall survival (log‐rank, P < .05).

CONCLUSIONS:

Adjuvant radiation may show promise in preventing tumor progression, but recurrence remains a common treatment outcome regardless of initial strategy. When safe and feasible, gross total resection should be pursued as an initial surgical strategy to maximize overall survival. The propensity of these tumors to metastasize makes detailed staging imaging necessary. Cancer 2011;. © 2011 American Cancer Society.     

Long‐term regional control and survival in patients with “low‐risk,” early stage oral tongue cancer managed by partial glossectomy and neck dissection without postoperative radiation

BACKGROUND:

The objectives of this study were to determine the incidence of locoregional failure in patients with low‐risk, early stage oral tongue squamous cell cancer (OTSCC) who undergo partial glossectomy and ipsilateral elective neck dissection without receiving postoperative radiation.

METHODS:

A combined database of patients with OTSCC who received treatment at Memorial Sloan‐Kettering Cancer Center and Princess Margaret Cancer Center from 1985 to 2005 was established. In total, 164 patients with pathologic T1‐T2N0 OTSCC who underwent partial glossectomy and ipsilateral elective neck dissection without postoperative radiation were identified. Patient‐related, tumor‐related, and treatment‐related characteristics were recorded. Local recurrence‐free survival, regional recurrence‐free survival, and disease‐specific survival were calculated by the Kaplan‐Meier method. Predictors of outcome were analyzed by univariate and multivariate analysis.

RESULTS:

At a median follow‐up of 66 months (range 1‐171 months), the 5‐year rates of local recurrence‐free survival, regional recurrence‐free survival, and disease‐specific survival were 89%, 79.9%, and 85.6%, respectively. Regional recurrence was ipsilateral in 61% of patients and contralateral in 39% of patients. The regional recurrence rate was 5.7% for tumors <4 mm and 24% for tumors ≥4 mm. Multivariate analysis indicated that tumor thickness was the only independent predictor of neck failure (regional recurrence‐free survival, 94% vs 72% [P = .02] for tumors <4 mm vs ≥4 mm, respectively). Patients who developed recurrence in the neck had a significantly poorer disease‐specific survival compared with those who did not (33% vs 97%; P < .0001).

CONCLUSIONS:

Patients with low‐risk, pathologic T1‐T2N0 OTSCC had a greater than expected rate of neck failure, with contralateral recurrence accounting for close to 40% of recurrences. Failure occurred predominantly in patients who had primary tumors that were ≥4 mm thick. Cancer 2013. © 2013 American Cancer Society.     

ALA fluorescent diagnosis of bladder cancer

Application of 5-aminolauvulin acid (ALA) fluorescence allows to detect not only exophytic tumors of the bladder but also flat, small tumors-satellites and preneoplastic changes of the bladder. 175 biopsies were performed in 53 patients with suspected superficial tumor of the bladder. 3 hours before surgery all the patients were intravesically instilled 50 ml 3% ALA solution. Cystoscopy employed white and blue light. Visual registration of exophytic masses and red fluorescence of the suspected sites was registered and consequently compared to the histological findings. 96 of 100 sites with malignancy/dysplasia showed red fluorescence. In 13% patients cancer and mucosal dysplasia were detected only under the blue light and were missed by standard cystoscopy. Residual red fluorescence of the resection margins was observed in 41% patients after TUR. Sensitivity of ALA-fluorescent detection reached 96%, specificity 52%. ALA-induced fluorescent diagnosis is more effective than standard cystoscopy. It is most effective in diagnosis of dysplasias, carcinoma in situ, flat, small, multiple superficial tumors of the bladder during primary TUR.     

Racial disparities in recurrence among patients with early‐stage endometrial cancer

BACKGROUND.

Population‐based studies suggest that, because of inequalities in treatment, black women with localized endometrial cancer have shorter survival compared with white women. The objective of the current investigation was to determine whether there is a racial disparity in outcome between black patients and white patients with early‐stage endometrial cancer treated similarly in a clinical trial setting.

METHODS.

A retrospective review of 110 black patients and 1049 white patients with stage I and II endometrial cancer (graded according to the International Federation of Gynecology and Obstetrics grading system) was performed using data from a randomized, placebo‐controlled trial performed by the Gynecologic Oncology Group that evaluated postoperative estrogen replacement therapy (ERT) and the risk of cancer recurrence. Demographic, pathologic, treatment, and outcome‐related data were collected and analyzed using regression and survival analysis.

RESULTS.

Estimates of recurrence‐free survival suggested that black patients may be more likely to have disease recurrence, particularly those receiving ERT. Within a median follow‐up of 3 years, 5 of 56 black patients with endometrial cancer in the ERT group were identified with recurrent disease compared with only 8 of 521 white patients. Adjusted for age, body mass index, and tumor grade, the relative risk of recurrence among blacks in the ERT group was 11.2 (95% confidence interval, 2.86‐43.59; P = .0005).

CONCLUSIONS.

The findings of the current study suggested that recurrence‐free survival may be shorter among black women with stage I endometrial cancer, even in a clinical trials setting in which patients receive similar treatment and follow‐up. This increased risk of recurrence appeared to be most evident in black women with endometrial cancer who maintained ERT after primary treatment. Cancer 2008. Published 2008 by the American Cancer Society.     

5‐Aminolevulinic acid is a promising marker for detection of anaplastic foci in diffusely infiltrating gliomas with nonsignificant contrast enhancement

BACKGROUND:

Because of intratumoral heterogeneity, diffusely infiltrating gliomas that lack significant contrast enhancement on magnetic resonance imaging are prone to tissue sampling error. Subsequent histologic undergrading may delay adjuvant treatments. 5‐Aminolevulinic acid (5‐ALA) leads to accumulation of fluorescent porphyrins in malignant glioma tissue, and is currently used for resection of malignant gliomas. The aim of this study was to clarify whether 5‐ALA might serve as marker for visualization of anaplastic foci in diffusely infiltrating gliomas with nonsignificant contrast enhancement for precise intraoperative tissue sampling.

METHODS:

5‐ALA was administered in 17 patients with diffusely infiltrating gliomas with nonsignificant contrast enhancement. During glioma resection, positive fluorescence was noted by a modified neurosurgical microscope. Intraoperative topographic correlation of focal 5‐ALA fluorescence with maximum ¹¹C‐methionine positron emission tomography uptake (PET_max) was performed. Multiple tissue samples were taken from areas of positive and/or negative 5‐ALA fluorescence. Histopathological diagnosis was established according to World Health Organization (WHO) 2007 criteria. Cell proliferation was assessed for multiregional samples by MIB‐1 labeling index (LI).

RESULTS:

Focal 5‐ALA fluorescence was observed in 8 of 9 patients with WHO grade III diffusely infiltrating gliomas. All 8 of 8 WHO grade II diffusely infiltrating gliomas were 5‐ALA negative. Focal 5‐ALA fluorescence correlated topographically with PET_max in all patients. MIB‐1 LI was significantly higher in 5‐ALA–positive than in nonfluorescent areas within a given tumor.

CONCLUSIONS:

The data indicate that 5‐ALA is a promising marker for intraoperative visualization of anaplastic foci in diffusely infiltrating gliomas with nonsignificant contrast enhancement. Unaffected by intraoperative brain shift, 5‐ALA may increase the precision of tissue sampling during tumor resection for histopathological grading, and therefore optimize allocation of patients to adjuvant treatments. Cancer 2010. © 2010 American Cancer Society.     

Novel endoscopic diagnosis for bladder cancer

Advances in endoscopic imaging technology may improve sensitivity for the detection of bladder cancer and provide a more complete understanding of the urothelial landscape, and it also may lead to improved short‐term and long‐term cancer control. Fluorescence cystoscopy requires intravesical administration of a photosensitizing agent (5‐aminolevulinic acid or hexaminolevulinate), and imaging with a blue‐light endoscopy system demonstrably improves the detection of papillary and flat bladder lesions compared with conventional white‐light cystoscopy. Prospective phase 3 clinical trials have demonstrated improved diagnostic ability, enhanced tumor resection, and a small but significant reduction in recurrence‐free survival. Optical coherence tomography delineates subsurface microarchitecture information about bladder lesions in real time and has the ability to discriminate between noninvasive and invasive cancers. Narrow‐band imaging may augment white‐light cystoscopy by providing increased contrast between normal and abnormal tissue on the basis of neovascularity. Confocal laser endoscopy has been applied to the urinary tract using thinner probes adapted from use in gastrointestinal malignancies and provides exquisite images at microscopic resolution. More technology is on the horizon that may further enhance our ability to detect and accurately stage bladder tumors and distinguish benign from malignant or dysplastic lesions. Cancer 2015;121:169–78 . © 2014 American Cancer Society.     

Depth of invasion determines the postresectional prognosis for patients with T1 extrahepatic cholangiocarcinoma

BACKGROUND:

We tested the hypothesis that in patients with T1 extrahepatic cholangiocarcinoma (EHC), prognosis postresection is significantly different for those with tumors that are limited to the mucosa than for those with tumors that have invaded (but not penetrated) the fibromuscular layer.

METHODS:

A retrospective analysis was conducted of 33 consecutive patients with pathologic T1 (pT1) EHC tumors. According to the depth of invasion, the pT1 tumors were divided into 2 groups: Group 1, tumors that were limited to the mucosa (mucosal tumors); and Group 2, tumors that had invaded (but not penetrated) the fibromuscular layer (fibromuscular layer‐invasive tumors). Long‐term outcomes after resection were compared between the 2 groups for a median follow‐up time of 175 months.

RESULTS:

Eighteen patients had mucosal tumors and 15 patients had tumors that had invaded the fibromuscular layer. None of the patients with mucosal tumors had lymphovascular invasion, whereas 3 of the patients with fibromuscular layer‐invasive tumors had lymphovascular invasion (P = .083). Overall survival after resection was better in Group 1 than in Group 2 (cumulative 10‐year survival rate, 100% vs 52%; P = .024). The rate of disease‐free survival after resection was higher in Group 1 than in Group 2 (cumulative disease‐free 10‐year survival rate, 100% vs 56%; P = .022).

CONCLUSIONS:

The long‐term outcome after resection for EHC is significantly better for patients with mucosal tumors than for patients with fibromuscular layer‐invasive tumors. This suggests that the depth of tumor invasion affects the postresection prognosis for patients with pT1 EHC. Cancer 2010. © 2010 American Cancer Society.     

Patterns of failure in patients with early onset (synchronous) resectable liver metastases from rectal cancer

BACKGROUND:

The optimal combination of available therapies for patients with resectable synchronous liver metastases from rectal cancer (SLMRC) is unknown, and the pattern of recurrence after resection has been poorly investigated. In this study, the authors examined recurrence patterns and survival after resection of SLMRC.

METHODS:

Consecutive patients with SLMRC (disease‐free interval, ≤12 months) who underwent complete resection of the rectal primary and liver metastases between 1990 and 2008 were identified from a prospective database. Demographics, tumor‐related variables, and treatment‐related variables were correlated with recurrence patterns. Competing risk analysis was used to determine the risk of pelvic and extrapelvic recurrence.

RESULTS:

In total, 185 patients underwent complete resection of rectal primary and liver metastases. One hundred eighty patients (97%) received chemotherapy during their treatment course, and 91 patients (49%) received pelvic radiation therapy either before (N = 65; 71.4%), or after (N = 26; 28.6%) rectal resection. The 5‐year disease‐specific survival rate was 51% for the entire cohort with a median follow‐up of 44 months for survivors. One hundred thirty patients (70%) developed a recurrence: Eighteen patients (10%) had recurrences in the pelvis in combination with other sites, and 7 of these (4%) had an isolated pelvic recurrence. Recurrence pattern did not correlate with survival. Competing risk analysis demonstrated that the likelihood of a pelvic recurrence was significantly lower than that of an extrapelvic recurrence (P < .001).

CONCLUSIONS:

Of the patients with SLMRC who developed recurrent disease, systemic sites were overwhelmingly more common than pelvic recurrences. The current results indicated that the selective exclusion of radiotherapy may be considered in patients who are diagnosed with simultaneous disease. Cancer 2012. © 2012 American Cancer Society.     

Tumor recurrence and malignant progression of gangliogliomas

BACKGROUND.

Most gangliogliomas (GGs) are benign tumors, but tumor recurrence and malignant progression are observed in some patients.

METHODS.

The authors analyzed their experience with 4 recurrent/progressive GGs (World Health Organization [WHO] grade I), 21 tumors with atypical features (WHO grade II), and 5 tumors with anaplastic histologic features (WHO grade III). Histopathologic findings (23 patients) were reviewed. The mean follow‐up was 5.9 years (median, 4.5 years; range, 0.5‐14.7 years).

RESULTS.

The 5‐year survival rates were only 79% for patients who had tumors with atypical features and 53% for patients who had WHO grade III tumors. Secondary glioblastomas were diagnosed in 5 of 11 patients (45%) who underwent surgery for tumor recurrence. Age at surgery <40 years (P = .007) was associated significantly with better overall survival (OS), but it was not associated with better progression‐free survival (PFS). Clinical presentation (drug‐resistant epilepsy vs all other patients with seizures vs no seizures) was associated significantly with better OS (P = .005) and PFS (P < .001). Patients who had extratemporal tumors had a significantly shorter PFS (P = .01) but not OS. A complete resection was correlated strongly with both OS (P = .002) and PFS (P = .001). Neuropathologic examination revealed the presence of a gemistocytic cell component (PFS, P = .025), a lack of protein droplets (OS, P = .04; PFS, P = .05), and focal tumor cell‐associated CD34 immunolabeling (OS, P = .03) as significant predictors of an adverse clinical course.

CONCLUSIONS.

The current data supported a 3‐tiered GG histopathologic grading system that included an intermediate diagnostic category (atypical GG, WHO grade II). Careful attention to histopathologic findings and clinical parameters usually will identify patients who are at risk for an adverse clinical course. Cancer 2008. © 2008 American Cancer Society.     

Soft tissue sarcomas of the popliteal fossa: a single-institution retrospective review

BACKGROUND:

Soft tissue sarcomas (STSs) arising from the popliteal fossa present a challenge with regard to local control of primary tumors. Due to concerns of functional morbidity and neurovascular compromise, there is debate about what represents the best therapy for these patients.

METHODS:

We conducted a retrospective medical record review of patients treated at The University of Texas M. D. Anderson Cancer Center for STS of the popliteal fossa from 1990 to 2008.

RESULTS:

There were 47 eligible patients, 28 of whom were male and 19 of whom were female. Synovial sarcoma was the most common diagnosis, with 12 cases. Most patients had T2b tumors (31 patients; 66%). The median duration of follow‐up was 3.8 years (range, 0.6‐17.9 years). The 5‐ and 10‐year overall survival rates were 63% and 51%, respectively. Metastasis at diagnosis was associated with poorer overall survival (5‐year overall survival, 74% versus 13%; P<.001) and poorer recurrence‐free survival (5‐year recurrence‐free survival, 51% versus 0%; P<.001) on univariate analysis. Radiation therapy improved local recurrence‐free survival (5‐year local recurrence‐free survival, 56% versus 17%; P = .004), whereas a trend was observed for surgical margin status (P = .07). Tumor size and neurovascular involvement did not influence outcome. Twenty‐two patients had recurrent disease, with 15 patients having local recurrence, and 16 patients died from progressive disease.

CONCLUSIONS:

Radiation therapy may play an important role in the treatment of popliteal fossa STS, but further study is needed to better define the best clinical application. Additional study is needed to re‐evaluate association of surgical margin status and outcome. Cancer 2011; © 2010 American Cancer Society.     

Carbonic anhydrase IX in bladder cancer

BACKGROUND:

The objective of this study was to evaluate the role of carbonic anhydrase IX (CAIX) in urothelial carcinoma of the bladder.

METHODS:

A tissue microarray was constructed that contained 724 tissue samples from 340 patients. Immunohistochemical staining was performed using the antibody MN‐75, the percentage of positive cells was evaluated, and their association with tumor (T) classification, grade, and survival was assessed.

RESULTS:

All normal urothelial tissue samples were negative for CAIX expression, whereas 71% of bladder cancers expressed CAIX. CAIX expression was higher in noninvasive (Ta) versus invasive (T1‐T4) tumors (P < .001), in low‐grade versus high‐grade bladder cancer (P < .001), and in metastases versus the corresponding primary tumor (P = .032). For patients with nonmuscle invasive carcinoma who underwent transurethral resection (TUR), higher CAIX expression was associated with poorer recurrence‐free survival (P = .001). In addition, for patients with T1 tumors who underwent TUR, higher CAIX expression conveyed a 6.5‐fold higher risk of progression into muscle‐invasive disease (P = .006). In patients who underwent cystectomy, higher CAIX expression was associated with worse overall survival (P = .003). Multivariate Cox models revealed that CAIX expression was the strongest, independent prognostic factor of recurrence‐free survival (hazard ratio, 2.29; P = .001) and overall survival (hazard ratio, 1.9; P < .001).

CONCLUSIONS:

CAIX was expressed differentially in noninvasive versus invasive tumors, in low‐grade versus high‐grade bladder cancer, and in primary tumors versus metastases. The current results indicated that CAIX is a strong predictor of recurrence, progression, and overall survival of patients with bladder cancer; and the integration of CAIX expression into conventional prognostic models significantly improved their predictive accuracy. The data suggest a tripartite role of CAIX as a diagnostic, prognostic, and therapeutic molecular marker in bladder cancer. Cancer 2009. © 2009 American Cancer Society.     

Brain metastasis from renal cell carcinoma: presentation, recurrence, and survival

BACKGROUND.

Patients with renal cell carcinoma brain metastases (RCCBM) are frequently excluded from trials and to the authors' knowledge no guidelines currently exist regarding central nervous system (CNS) surveillance or treatment. The objective of the current study was to assist in the creation of treatment guidelines.

METHODS.

Patients undergoing evaluation for RCCBM from 1989 to 2006 were identified. Their characteristics, symptoms, pathologic variables, number and size of RCCBM, CNS treatment, CNS recurrence, overall survival, and use of systemic therapy were reviewed.

RESULTS.

A total of 138 patients were identified with RCCBM, of whom 92% had clear cell RCC and 95% had synchronous extracranial metastases. CNS symptoms were noted in 67% of patients. Symptomatic CNS tumors were larger (2.1 cm vs 1.3 cm; P < .001) and more frequently required a craniotomy (P < .001). The median overall survival after a diagnosis of RCCBM was 10.7 months; the 1‐year, 2‐year, and 5‐year survival rates were 48%, 30%, and 12%, respectively. Median CNS recurrence was 9 months after RCCBM treatment. The initial number of tumors (>1 tumor) was found to be an independent predictor of CNS recurrence (hazards ratio of 3.72; P < .001). Those patients with 1 and >1 lesion had a median CNS recurrence‐free survival of 13 months and 4 months, respectively (P < .001). Patients receiving interleukin‐2 after CNS treatment had a response rate of 17%.

CONCLUSIONS.

Patients with metastatic RCC should undergo CNS screening to allow the identification of smaller lesions that are more amenable to treatment. Those patients with solitary RCCBM are less likely to develop CNS recurrence after local therapy. Selected patients with good performance status may exhibit prolonged survival and should be offered aggressive therapy. Cancer 2008. © 2008 American Cancer Society.     

¹¹C-methionine uptake and intraoperative 5-aminolevulinic acid-induced fluorescence as separate index markers of cell density in glioma: a stereotactic image-histological analysis

BACKGROUND:

The extent of tumor resection is acknowledged as 1 of the prognostic factors for glioma. 5‐Aminolevulinic acid (5‐ALA)‐induced fluorescence guidance and neuronavigation integrated with ¹¹C‐methionine positron emission tomography (PET) are widely utilized under the expectation of improving the extent of resection. These 2 novel approaches are beneficial for glioma resections, and the combination of these approaches appears rational. However, biological characteristics reflecting 5‐ALA‐induced fluorescence and ¹¹C‐methionine uptake have not been clearly elucidated, and studies about the relationship between 5‐ALA‐induced fluorescence and ¹¹C‐methionine uptake have been limited. The present study aimed to clarify this issue.

METHODS:

Data from 11 consecutive patients harboring astrocytic tumors were analyzed: 2 grade II and 2 grade III, and 7 grade IV tumors were included. Thirty samples from these patients were obtained from the relative periphery of each tumor. Relationships among histology, 5‐ALA‐induced fluorescence and ¹¹C‐methionine uptake were analyzed by stereotactic sampling and image analysis.

RESULTS:

Uptake of ¹¹C‐methionine correlated with cell density (R² = 0.322, P = .0059). Cell density was higher in fluorescence‐positive areas than in negative areas (2760 ± 1080 vs 1450 ± 1380/mm², P = .0132). Although both ¹¹C‐methionine uptake and fluorescence seemed to correlate with cell density, no significant difference in ¹¹C‐methionine uptake was seen between fluorescence‐positive and ‐negative areas (P = .367). Multiple linear regression analysis revealed ¹¹C‐methionine uptake and 5‐ALA‐induced fluorescence as independent indices for tumor cell density.

CONCLUSIONS:

These results indicate that 5‐ALA fluorescence and ¹¹C‐methionine PET image are separate index markers for cytoreduction surgery of gliomas. Cancer 2011;. © 2011 American Cancer Society.     

Favorable prognosis in patients with T1a/T1bN0 triple-negative breast cancers treated with multimodality therapy

BACKGROUND:

The authors evaluated the clinical characteristics, natural history, and outcomes of patients who had ≤1 cm, lymph node‐negative, triple‐negative breast cancer (TNBC).

METHODS:

After excluding patients who had received neoadjuvant therapy, 1022 patients with TNBC who underwent definitive breast surgery during 1999 to 2006 were identified from an institutional database. In total, 194 who had lymph node‐negative tumors that measured ≤1 cm comprised the study population. Clinical data were abstracted, and survival outcomes were analyzed.

RESULTS:

The median follow‐up was 73 months (range, 5‐143 months). The median age at diagnosis was 55.5 years (range, 27‐84 years). Tumor (T) classification was microscopic (T1mic) in 16 patients (8.2%), T1a in 49 patients (25.3%), and T1b in 129 patients (66.5%). Most tumors were poorly differentiated (n = 142; 73%), lacked lymphovascular invasion (n = 170; 87.6%), and were detected by screening (n = 134; 69%). In total, 129 patients (66.5%) underwent breast‐conserving surgery, and 65 patients (33.5%) underwent mastectomy. One hundred thirteen patients (58%) received adjuvant chemotherapy, and 123 patients (63%) received whole‐breast radiation. The patients who received chemotherapy had more adverse clinical and disease features (younger age, T1b tumor, poor tumor grade; all P < .05). Results from testing for the breast cancer (BRCA) susceptibility gene were available for 49 women: 19 women had BRCA1 mutations, 7 women had BRCA2 mutations, and 23 women had no mutations. For the entire group, the 5‐year local recurrence‐free survival rate was 95%, and the 5‐year distant metastasis‐free survival rate was 95%. There was no difference between patients with T1mic/T1a tumors and patients with T1b tumors in the distant recurrence rate (94.5% vs 95.5%, respectively; P = .81) or in the receipt of chemotherapy (95.9% vs 94.5%, respectively; P = .63).

CONCLUSIONS:

Excellent 5‐year locoregional and distant control rates were achievable in patients with TNBC who had tumors ≤1.0 cm, 58% of whom received chemotherapy. These results identified a group of patients with TNBC who had favorable outcomes after early detection and multimodality treatment. Cancer 2012. © 2012 American Cancer Society.     

Clinical utility of the new American Joint Committee on Cancer staging system for gastrointestinal stromal tumors: current overall survival after primary tumor resection

BACKGROUND:

The objectives of the current study were to assess the reliability of the new revision of the American Joint Committee on Cancer (AJCC) staging system for gastrointestinal stromal tumors (GISTs) based on the National Comprehensive Cancer Network‐Armed Forces Institute of Pathology risk classification and to analyze the factors that influence after resection for primary GISTs in 2 AJCC groups: patients with GISTs originating from the stomach and omentum (G‐GISTs) and patients with other primary GISTs located mainly in the small bowel (nongastric GISTs [NG‐GISTs]).

METHODS:

The authors prospectively analyzed a group of 640 patients with primary, CD117‐positive GISTs who underwent surgery with curative intention (R0/R1 resection), including 340 G‐GISTs (55.5%) and 300 NG‐GISTs (44.5%). Factors were explored that had an effect on disease‐free survival time (DFS), which was calculated from the date of radical operation to the date of recurrence or last follow‐up. The median follow‐up was 39 months.

RESULTS:

Compared with NG‐GISTs, G‐GISTs were characterized by a significantly lower median size (5.3 cm and 8.5 cm, respectively; P < .0001) and lower mitotic activity (median, 3 in 50 high‐power fields [HPF] vs 5 in 50 HPF; P < .0001), and they were diagnosed in older patients (median age, 62 years vs 57 years; P = .002). The most commonly detected mutations in G‐GIST were those located in KIT exon 11 (60.5%) and platelet‐derived growth factor receptor alpha (PDGFRA) exon 18 (19%) versus KIT exons 11 and 9 in NG‐GISTs (72% and 17.4%, respectively). The prognosis of patients who had G‐GISTs was significantly better compared that of patients who had NG‐GISTs, with 5‐year DFS rates of 69% (median, 83 months) versus 43% (median, 33 months), respectively (P < .00001). The most significant prognostic factors that correlated with shorter DFS in both G‐GISTs and NG‐GISTs were primary tumor size >5 cm and >10 cm (P < .0001) and mitotic index >5 in 50 HPF and >10 in 50 HPF (P < .0001). The 5‐year DFS rates in G‐GISTs according to AJCC stage categories were as follows: 96% for stage IA tumors, 92% for stage IB tumors, 51% for II tumors, 22% for stage IIIA tumors, and 22% for stage IIIB tumors (P < .0001). The 5‐year DFS rates in NG‐GISTs according to AJCC categories were as follows: 92% for stage I tumors, 66% for stage II tumors, 28% for IIIA tumors, and 16% for IIIB tumors (P < .0001). The high prognostic significance of the AJCC classification also was confirmed for overall survival data, including the impact of therapy with tyrosine kinase inhibitors.

CONCLUSIONS:

The reliability of AJCC risk classification after resection of primary GIST was confirmed for DFS and overall survival. Patients with primary G‐GISTs had a better prognosis than patients with NG‐GISTs. In both groups, primary tumor size and mitotic activity were the most important prognostic factors in terms of DFS. Cancer 2011;. © 2011 American Cancer Society.     

Durable oncologic outcomes after radiofrequency ablation

BACKGROUND:

Long‐term oncologic outcomes for renal thermal ablation are limited. The authors of this report present their experience with radiofrequency ablation (RFA) therapy for 243 small renal masses (SRMs) over the past 7.5 years.

METHODS:

The authors' institutional, prospectively maintained RFA database was reviewed to determine intermediate and long‐term oncologic outcomes for patients with SRMs (generally <4 cm) who underwent RFA. Particular attention was placed on patients who had a minimum 3 years of follow‐up. Patients were excluded from the analysis if they had received previous treatment for renal cell carcinoma (RCC) on the ipsilateral kidney or if they did not have at least 1 imaging study available for follow‐up.

RESULTS:

Two hundred eight patients (with 243 SRMs) who had no evidence of previous ipsilateral renal cancer treatment underwent RFA and had follow‐up imaging studies available for review. Overall, tumor size averaged 2.4 cm, and follow‐up ranged from 1.5 months to 90 months (mean, 27 months). Of the 227 tumors (93%) that underwent preablation biopsy, RCC was confirmed in 79%. The initial treatment success rate was 97%, and the overall 5‐year recurrence‐free survival rate was 93% (90% for 160 patients who had biopsy‐proven RCC). During follow‐up, 3 patients developed metastatic disease, and 1 patient died of RCC, yielding 5‐year actuarial metastasis‐free and cancer‐specific survival rates of 95% and 99%, respectively.

CONCLUSIONS:

RFA provided successful treatment of SRMs and produced a low rate of recurrence as well as prolonged metastasis‐free and cancer‐specific survival rates at 5 years after treatment. Although longer term follow‐up of RFA will be required to determine late recurrence rates, the current results indicated a minimal risk of disease recurrence in patients who are >3 years removed from RFA. Cancer 2010. © 2010 American Cancer Society.     

Insulin‐like growth factor‐1 receptor and phosphorylated AKT‐serine 473 expression in 132 resected thymomas and thymic carcinomas

BACKGROUND:

Thymic malignancies are rare tumors. The insulin‐like growth factor‐1 (IGF‐1)/IGF‐1 receptor (IGF‐1R) system is involved in the development of the thymus. IGF‐1R expression in thymic epithelial malignancies is unknown.

METHODS:

The authors investigated the expression of IGF‐1R and phosphorylated AKT serine 473 (p‐AKT) by using immunohistochemistry and examined the clinicopathologic correlations in a retrospective, single‐institution surgical series of 132 patients with thymic epithelial malignancies.

RESULTS:

Earlier disease stage, less aggressive histologic types, and complete resection were significant positive prognostic factors for disease‐related survival and progression‐free survival, and being a woman was a better prognostic factor for disease‐related survival. IGF‐1R and p‐AKT protein levels were expressed in 20% and 36% of thymic tumors, respectively. Both markers were expressed more commonly in recurrent disease than in primary tumors, in more aggressive subtypes, and in more advanced disease stages. There was a trend toward better survival and progression‐free survival in patients who were negative for IGF‐1R or p‐AKT expression in the whole series. When only the 91 primary tumors, IGF1R expression was associated with worse progression‐free survival (P < .001).

CONCLUSIONS:

The current retrospective analysis demonstrated that disease stage, tumor histology, sex, and resection type were major prognostic factors in the survival of patients with thymic malignancies. The expression levels of IGF‐1R and p‐AKT in thymic tumors suggested that IGF‐1R is a potential target for treatment. Cancer 2010. Published 2010 by the American Cancer Society.     

Synchronous bilateral Wilms tumor

BACKGROUND:

The optimal management of bilateral Wilms tumor (BWT) is challenging, and their survival is lower than for unilateral tumors. This report discusses a large series of BWTs treated in Italy in the last 2 decades.

METHODS:

This analysis concerns patients with synchronous BWT registered at Associazione Italiana Ematologia Oncologia Pediatrica (AIEOP) centers between 1990 and 2011; details on their treatment and outcome are presented and discussed.

RESULTS:

Ninety BWTs were registered in the AIEOP Wilms tumor database. Preoperative chemotherapy was given for a median 12 weeks before definitive tumor resection was attempted. Forty‐eight percent of the patients had preservation of bilateral renal parenchyma. The proportion of bilateral nephron‐sparing surgeries was not higher in the 37 patients initially given doxorubicin/vincristine/actinomycin D (32%) than in the 43 children receiving vincristine/actinomycin D alone (58%). The 4‐year disease‐free survival rate was 66.5% ± 5% and overall survival was 80% ± 5% for the cohort as a whole. The 4‐year disease‐free survival (overall survival) for 18 children with diffuse anaplasia or postchemotherapy blastemal‐type tumors was 51% ± 13% (62% ± 13%), as opposed to 72% ± 3% (88% ± 4%) for 68 children with a favorable histology (log‐rank P = .04 [P = .007]).

CONCLUSIONS:

These results provide further evidence that the optimal duration and choice of drugs for preoperative chemotherapy remain an open question. Outcome remained significantly worse for BWT than for unilateral Wilms tumor. To enable the conservative treatment of as many affected kidneys as possible, only centers with experience in BWT should manage such cases. Cancer 2013. © 2013 American Cancer Society.     

The impact of symptom interference using the MD Anderson Symptom Inventory-Brain Tumor Module (MDASI-BT) on prediction of recurrence in primary brain tumor patients

BACKGROUND:

Tumor grade, age, extent of resection, and performance status are established prognostic factors for survival in primary brain tumor (PBT) patients. Development of disease‐related symptoms is predictive of tumor recurrence in other cancers but has not been reported in the PBT population.

METHODS:

A cross‐sectional sample of 294 PBT patients participated. Progression was based on the radiologist report of the magnetic resonance imaging (MRI). The relation of clinical variables (age, extent of resection, tumor grade, and Karnofsky performance status [KPS]) and MD Anderson Symptom Inventory‐Brain Tumor Module (MDASI‐BT) mean symptom and interference subscales with progression was examined using logistic regression.

RESULTS:

The study enrolled more men (60%, n = 175); median age was 46 years. The majority had less than a gross total resection (n = 186, 64%), and a good KPS (KPS ≥ 90) (N = 208). The majority had a grade 3 or 4 tumor (n = 199) and 24% of patients had recurrence. Tumor grade and activity‐related interference were significantly related to progression. Patients with tumor grade 4 were 2.4 times more likely to have recurrence (95% CI, 1.2‐5.; P < .015). Patients with significant (ratings of ≥5) activity‐related interference were 3.8 times more likely to have recurrence (95% CI, 2.14‐6.80; P < .001). Mean activity‐related score was 4.8 for those with progression on MRI and 2.2 for those with stable disease.

CONCLUSIONS:

Significant activity‐related interference and tumor grade were associated with recurrence but not KPS, age, or extent of resection. These results provide preliminary support for the use of symptom interference in assessment of disease status. Because the authors used a cross‐sectional sample, future studies evaluating change over time are needed. Cancer 2011. © 2011 American Cancer Society.