Diagnosis Of Distant Metastatic Disease Research Articles

Selective use of radiological staging in node-positive stage II breast cancer patients may have a role in treatment.

Advanced-staging radiography is used inconsistently for patients with early-stage (stage I + II) breast cancer. However, accurate and appropriate staging of newly diagnosed breast cancer may significantly impact treatment decisions. Four hundred and ninety-nine patients with stages II and III breast cancer were seen in the breast service at Waitemata DHB, New Zealand from 2013 to 2018 were enrolled in the study and audited for radiological staging. One hundred and two stage II patients had computed tomography (CT) at baseline; 88 of 102 (86%) of stage II patients were node-positive (≥N1) with six patients (6.8%) having distant metastatic disease, and were upstaged to stage IV. Fifty-two stage III patients out of 72 (72%) had baseline staging CTs. Nine out of 52 patients (17%) of stage III patients were upstaged to stage IV. Despite guideline recommendations, baseline staging for T4 disease (stage IIIB) was poor, with only 7 out of 13 patients with stage IIIB disease radiologically staged. Consideration for baseline radiological staging should be given to stages II and III, cN1 breast cancer patients, in which diagnosis of distant metastatic disease would change the treatment plan. Regional guidelines for baseline radiological staging for breast cancer patients may have an impact on patient management in breast cancer patients.

Predictive Model to Guide Brain Magnetic Resonance Imaging Surveillance in Patients With Metastatic Lung Cancer: Impact on Real-World Outcomes.

Brain metastasis is common in lung cancer, and treatment of brain metastasis can lead to significant morbidity. Although early detection of brain metastasis may improve outcomes, there are no prediction models to identify high-risk patients for brain magnetic resonance imaging (MRI) surveillance. Our goal is to develop a machine learning-based clinicogenomic prediction model to estimate patient-level brain metastasis risk. A penalized regression competing risk model was developed using 330 patients diagnosed with lung cancer between January 2014 and June 2019 and followed through June 2021 at Stanford HealthCare. The main outcome was time from the diagnosis of distant metastatic disease to the development of brain metastasis, death, or censoring. Among the 330 patients, 84 (25%) developed brain metastasis over 627 person-years, with a 1-year cumulative brain metastasis incidence of 10.2% (95% CI, 6.8 to 13.6). Features selected for model inclusion were histology, cancer stage, age at diagnosis, primary site, and RB1 and ALK alterations. The prediction model yielded high discrimination (area under the curve 0.75). When the cohort was stratified by risk using a 1-year risk threshold of > 14.2% (85th percentile), the high-risk group had increased 1-year cumulative incidence of brain metastasis versus the low-risk group (30.8% v 6.1%, P < .01). Of 48 high-risk patients, 24 developed brain metastasis, and of these, 12 patients had brain metastasis detected more than 7 months after last brain MRI. Patients who missed this 7-month window had larger brain metastases (58% v 33% largest diameter > 10 mm; odds ratio, 2.80, CI, 0.51 to 13) versus those who had MRIs more frequently. The proposed model can identify high-risk patients, who may benefit from more intensive brain MRI surveillance to reduce morbidity of subsequent treatment through early detection.

Indication for radioiodine remnant ablation in differentiated thyroid cancer patients: does 2018 Italian consensus change anything?

We speculated that radioiodine remnant ablation (RRA) could be performed less frequently in differentiated thyroid cancer (DTC) patients, if the recommendations of the 2018 Italian Consensus (ITA) were applied in clinical practice. Therefore, we compared the ITA indications for RRA with the recommendations by the 2015 American Thyroid Association guidelines (ATA). We retrospectively evaluated 380 consecutive DTC patients treated with surgery and RRA, followed at the Section of Endocrinology, University of Siena, Italy from January 2006 to December 2019. Using ITA a significant increase of DTC patients classified as low or high risk and a significant decrease of patients defined at intermediate risk were observed (p < 0.0001). Consequently, the percentage of patients without routinary indication for RRA (47.4%, versus 38.2%, p < 0.0001) and those with a definite indication for RRA (8.2 versus 1.8%, p < 0.0001) was significantly higher compared to ATA. Moreover, using ITA the percentage of patients with a selective use of RRA was lower in comparison to ATA (44.7% versus 60%, p < 0.0001). Nevertheless, the prevalence of distant metastases, at post-ablative whole body scan, in patients without indication for RRA, was not different using either ATA or ITA (2.1% and 1.1% respectively, p = 0.37). The use of ITA Consensus, in clinical practice, increases significantly the number of patients for whom RRA is not routinely indicated in comparison to ATA guidelines but without differences in delaying the diagnosis of distant metastatic disease.

Trastuzumab and survival of patients with metastatic breast cancer.

Prognosis of Her2-positive breast cancer has changed since the introduction of trastuzumab for treatment in metastatic and early breast cancer. It was described to be even better compared to prognosis of Her2-negative metastatic breast cancer. The purpose of this study was to evaluate the effect of trastuzumab in our cohort. Besides the effect of adjuvant pretreatment with trastuzumab on survival of patients with metastatic Her2-positive breast cancer was analyzed. All patients with primary breast cancer of the Regional Breast Cancer Center Dresden diagnosed during the years 2001-2013 were analyzed for treatment with or without trastuzumab in the adjuvant and in the metastatic treatment setting using Kaplan-Meier survival estimation and Cox regression. Age and tumor stage at time of first diagnosis of breast cancer as well as hormone receptor status, grading, time, and site of metastasis at first diagnosis of distant metastatic disease were analyzed. Of 4.481 female patients with primary breast cancer, 643 presented with metastatic disease. Her2-positive status was documented in 465 patients, including 116 patients with primary or secondary metastases. Median survival of patients with Her2-positive primary metastatic disease was 3.0years (95% CI 2.3-4.0). After adjustment for other factors, survival was better in patients with Her2-positive breast cancer with trastuzumab therapy compared to Her2-negative metastatic disease (HR 2.10; 95% CI 1.58-2.79). Analysis of influence of adjuvant therapy with and without trastuzumab by Kaplan-Meier showed a trend for better survival in not pretreated patients. Median survival was highest in hormone receptor-positive Her2-positive (triple-positive) primary metastatic breast cancer patients with 3.3years (95% CI 2.3-4.6). Prognosis of patients with Her2-positive metastatic breast cancer after trastuzumab treatment is more favorable than for Her2-negative breast cancer. The role of adjuvant chemotherapy with or without trastuzumab warrants further research. Survival is best in triple-positive metastatic breast cancer. This will effect counseling at the time of first diagnosis of metastatic breast cancer.

Clinical outcomes based on multigene profiling in metastatic breast cancer patients.

BACKGROUNDIdentifying the clinical impact of recurrent mutations can help define their role in cancer. Here, we identify frequent hotspot mutations in metastatic breast cancer (MBC) patients and associate them with clinical outcomes.PATIENTS AND METHODSHotspot mutation testing was conducted in 500 MBC patients using an 11 gene (N = 126) and/or 46 or 50 gene (N = 391) panel. Patients were stratified by hormone receptor (HR) and human epidermal growth factor 2 (HER2) status. Clinical outcomes were retrospectively collected.RESULTSHotspot mutations were most frequently detected in TP53 (30%), PIK3CA (27%) and AKT1 (4%). Triple-negative breast cancer (TNBC) patients had the highest incidence of TP53 (58%) and the lowest incidence of PIK3CA (9%) mutations. TP53 mutation was associated with shorter relapse-free survival (RFS) (median 22 vs 42months; P < 0.001) and overall survival (OS) from diagnosis of distant metastatic disease (median 26 vs 51months; P < 0.001). Conversely, PIK3CA mutation was associated with a trend towards better clinical outcomes including RFS (median 41 vs 30months; P = 0.074) and OS (52 vs 40months; P = 0.066). In HR-positive patients, TP53 mutation was again associated with shorter RFS (median 30 vs 46months; P = 0.017) and OS (median 30 vs 55months; P = 0.001). When multivariable analysis was performed for RFS and OS, TP53 but not PIK3CA mutation remained a significant predictor of outcomes in the overall cohort and in HR-positive patients.CONCLUSIONSClinical hotspot sequencing identifies potentially actionable mutations. In this cohort, TP53 mutation was associated with worse clinical outcomes, while PIK3CA mutation did not remain a significant predictor of outcomes after multivariable analysis.

Prognosis of Mucosal, Uveal, Acral, Nonacral Cutaneous, and Unknown Primary Melanoma From the Time of First Metastasis

Subtypes of melanoma, such as mucosal, uveal, and acral, are believed to result in worse prognoses than nonacral cutaneous melanoma. After a diagnosis of distant metastatic disease, however, the overall survival of patients with mucosal, uveal, acral, nonacral cutaneous, and unknown primary melanoma has not been directly compared. We conducted a single-center, retrospective analysis of 3,454 patients with melanoma diagnosed with distant metastases from 2000 to 2013, identified from a prospectively maintained database. We examined melanoma subtype, date of diagnosis of distant metastases, age at diagnosis of metastasis, gender, and site of melanoma metastases. Of the 3,454 patients (237 with mucosal, 286 with uveal, 2,292 with nonacral cutaneous, 105 with acral cutaneous, and 534 with unknown primary melanoma), 2,594 died. The median follow-up was 46.1 months. The median overall survival for those with mucosal, uveal, acral, nonacral cutaneous, and unknown primary melanoma was 9.1, 13.4, 11.4, 11.7, and 10.4 months, respectively. Patients with uveal melanoma, cutaneous melanoma (acral and nonacral), and unknown primary melanoma had similar survival, but patients with mucosal melanoma had worse survival. Patients diagnosed with metastatic melanoma in 2006-2010 and 2011-2013 had better overall survival than patients diagnosed in 2000-2005. In a multivariate model, patients with mucosal melanoma had inferior overall survival compared with patients with the other four subtypes. Additional research and advocacy are needed for patients with mucosal melanoma because of their shorter overall survival in the metastatic setting. Despite distinct tumor biology, the survival was similar for those with metastatic uveal melanoma, acral, nonacral cutaneous, and unknown primary melanoma. Uveal, acral, and mucosal melanoma are assumed to result in a worse prognosis than nonacral cutaneous melanoma or unknown primary melanoma. No studies, however, have been conducted assessing the overall survival of patients with these melanoma subtypes starting at the time of distant metastatic disease. The present study found that patients with uveal, acral, nonacral cutaneous, and unknown primary melanoma have similar overall survival after distant metastases have been diagnosed. These findings provide information for oncologists to reconsider previously held assumptions and appropriately counsel patients. Patients with mucosal melanoma have worse overall survival and are thus a group in need of specific research and advocacy.

Abstract P3-12-12: Incidence of internal mammary node, sternum, and manubrium failure as detected by FDG-18 PET/CT

Abstract Introduction: Elective radiotherapy to the internal mammary (IM) lymph nodes remains an ongoing subject of debate. While the incidence of occult IM involvement on extended mastectomy ranges from 15-65%, reported rates of IM failure are substantially lower (approximately 1%). Interest in this subject has resurfaced recently as randomized trials have shown a survival benefit to adjuvant regional node irradiation including the IM chain. The mechanism by which extended field radiotherapy leads to improved systemic outcomes has not been clearly demonstrated and the degree of benefit directly attributable to IM irradiation remains to be seen. We hypothesized that the IM lymphatic chain may provide a direct route for tumor cell dissemination into the the sternum or manubrium. As such, sternal metastases may be a manifestation of IM involvement rather than true hematogenous metastases. We sought to better elucidate patterns of failure by evaluating the incidence and timing of IM, sternal, or manubrial involvement identified by PET/CT imaging following diagnosis of metastatic breast cancer. Patients and Methods: Between 2007 and 2014, 96 patients with invasive breast cancer were found to have metastatic disease as diagnosed on FDG-18 PET/CT. Site of recurrence was scored as breast/chest wall, axilla/supraclav, IM chain, sternum/manubrium, or distant. IM or sternum/manubrium failure was scored as isolated (occurring without distant metastatic disease), synchronous (involved at initial diagnosis of distant metastatic disease), or metachronous (involved at any time after diagnosis of metastatic disease). Results: Isolated IM failures were observed in 3.1% of patients while isolated sternum/manubrium failures were recorded in 7.3% of patients. Isolated involvement of the sternum/manubrium or IM nodes occurred in 11.4%. The rate of synchronous IM failure was 11.4% with the rate of metachronous failure being 13.5%. The rate of synchronous sternum/manubrium failure was 17.7% with the rate of metachronous failure being 23.9%. The incidence of sternum/manubrium or IM involvement at the initial diagnosis of distant metastatic disease was 29.2% with the rate of involvement at any point increasing to 36.5%. Conclusion: The rate of internal mammary node failure by PET/CT at the time of metastatic diagnosis is higher than the incidence reported in previous trials. This discrepancy is likely due increased sensitivity of PET/CT and the difficulty of accurately assessing this region once patients have been found to have metastatic disease. Interestingly, sternum and manubrium were more often the first site of recurrence than the IM nodes. This could be due to a tropism of hematogenous metastases for these bones or could represent direct tumor cell dissemination from the internal mammary chain. This is of special interest as this region is incidentally included in the radiotherapy fields when targeting the IM nodes. Overall, our findings suggest that historic patterns of failure studies may underestimate the local benefit of internal mammary node radiotherapy. Citation Format: Grow JL, Choudhary G, Kuo P, Livingston RB, Gonzalez VJ. Incidence of internal mammary node, sternum, and manubrium failure as detected by FDG-18 PET/CT. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P3-12-12.

Abstract P2-06-11: Wild type N-Ras, overexpressed in basal-like breast cancer, promotes tumor formation by inducing IL8 secretion via JAK2 activation

Abstract "Basal-like" breast cancer (BLBC) is a very aggressive subtype of breast cancer. BLBC has very poor prognosis — median time to distant recurrence is just 2.6 years vs. 5 years overall, and survival time from diagnosis of distant metastatic disease is 9 months vs. 22 months. BLBC tumors usually do not express ER, Her2, or progesterone receptor. As such, they cannot be treated by the current targeted therapies, which target these molecules. What drive the formation and progression of BLBCs is largely unclear. Ras GTPases are best known for mediating growth factor signaling. Oncogenic mutations in the RAS genes, K-RAS in particular, are found in more than 30% of human tumors. Surprisingly, oncogenic RAS mutations are rare in breast cancer. However, we found that wild-type N-RAS is overexpressed in BLBCs, possibly partly via promoter demethylation, but not in other breast cancer subtypes. Repressing N-RAS inhibits transformation and tumor growth, while overexpressing it enhances these processes even in preinvasive BLBC cells. In contrast, in breast cancer cells of other subtypes, repressing N-RAS expression does not affect growth and transforming activities. We identified N-Ras-responsive genes, most of which encode chemokines and cytokines, e.g., IL8. High expression levels of these N-Ras-responsive genes as well as of N-RAS itself in tumors correlate with poor patient outcome. N-Ras, but not K-Ras, induces IL8 by binding and activating the cytoplasmic pool of JAK2; IL8 then acts on both the cancer cells and stromal fibroblasts. In conclusion, N-Ras drives BLBC by promoting transformation in epithelial cells, which may in turn remodel the tumor microenvironment to create a proinvasive state. Although oncogenic mutations affecting RAS are common in many other human cancers, tumorigenesis in an important subset of breast cancers is driven instead by increasing activity of wild-type N-Ras. Thus, to fully assess the impact of Ras on tumorigenesis, the role of wild-type as well as mutant Ras proteins must be carefully examined. Citation Format: Zheng Z-Y, Bu W, Tian L, Fan C, Gao X, Zhang X, Yu C, Wang H, Liao Y-H, Li Y, Lewis MT, Edwards D, Zwaka TP, Hilsenbeck SG, Medina D, Perou CM, Creighton CJ, Zhang XH, Chang EC. Wild type N-Ras, overexpressed in basal-like breast cancer, promotes tumor formation by inducing IL8 secretion via JAK2 activation. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P2-06-11.

(18)F-FDG PET/CT to assess response and guide risk-stratified follow-up after chemoradiotherapy for oropharyngeal squamous cell carcinoma.

To evaluate the use of (18)F-FDG PET/CT as the principal investigation to assess tumour response, to determine the need for further surgery and to guide follow-up following radical chemoradiotherapy for stage III/IV oropharyngeal squamous cell carcinoma (OPSCC). A retrospective analysis was undertaken in 146 patients treated at our centre with radical chemoradiotherapy for OPSCC and who had a PET/CT scan to assess response. According to the PET/CT findings, patients were divided into four groups and recommendations: (1) complete metabolic response (enter clinical follow-up); (2) low-level uptake only (follow-up PET/CT scan in 12weeks); (3) residual uptake suspicious for residual disease (further investigation with or without neck dissection); and (4) new diagnosis of distant metastatic disease (palliative treatment options). The initial PET/CT scan was performed at a median of 12.4weeks (range 4.3 - 21.7weeks) following treatment. Overall sensitivity and specificity rates were 92.0% (74.0 - 99.0%) and 85% (77.5 - 90.9%). Of the 146 patients, 90 (62%) had a complete response and had estimated 3-year overall and disease-free survival rates of 91.9% (85.6 - 98.2%) and 85.6% (78.0 - 93.2%), respectively, 17 (12%) had residual low-level uptake only (with two having confirmed residual disease on subsequent PET/CT, both surgically salvaged), 30 (21%) had suspicious residual uptake (12 proceeded to neck dissection; true positive rate at surgery 33%). HPV-positive patients with reassuring PET/CT findings had an estimated 3-year progression-free survival rate of 91.7% (85.2 - 98.2%), compared with 66.2% (41.5 - 90.9%) of HPV-negative patients. A strategy of using PET/CT results alongside clinical examination to help select patients for salvage surgery appears successful. Despite a complete response on the 12-week PET/CT scan, HPV-negative patients have a significant risk of disease relapse in the following 2years and further studies to assess whether surveillance imaging in this group could improve outcomes are warranted.

Abstract 2139: Wild type N-Ras, overexpressed in basal-like breast cancer, promotes tumor formation by inducing IL8 secretion via JAK2 activation

Abstract “Basal-like” breast cancer (BLBC) is the most aggressive breast cancer subtype, with a very poor prognosis _ median time to distant recurrence is just 2.6 years vs. 5 years overall, and survival time from diagnosis of distant metastatic disease is 9 months vs. 22 months. BLBC tumors usually do not express ER, Her2, or progesterone receptor. As such, they cannot be treated by the current targeted therapies, which target these molecules. What drive the formation and progression of BLBCs is largely unclear. Ras GTPases are best known for mediating growth factor signaling, and oncogenic mutations in the RAS genes, and K-RAS in particular, are found in more than 30% of human tumors. Surprisingly, oncogenic RAS mutations are rare in breast cancer. However, we found that wild-type N-RAS is overexpressed in BLBCs, partly via promoter demethylation, but not in other breast cancer subtypes. Repressing N-RAS inhibits transformation and tumor growth, while overexpression enhances these processes even in preinvasive BLBC cells. In contrast, repressing N-RAS expression does not affect growth and transforming activities of breast cancer cells of other subtypes. We identified N-Ras-responsive genes, most of which encode chemokines, e.g., IL8. High expression levels of these N-Ras-responsive genes as well as of N-RAS itself in tumors correlate with poor patient outcome. N-Ras, but not K-Ras, induces IL8 by binding and activating the cytoplasmic pool of JAK2; IL8 then acts on both the cancer cells and stromal fibroblasts. Thus N-Ras drives BLBC by promoting transformation in epithelial cells, which in turn remodels the tumor microenvironment to create a proinvasive state. These results illustrate an N-Ras-dependent convergence between the growth factor and cytokine pathways to enable efficient transformation of epithelial cells, which then orchestrate the remodeling of the tumor microenvironment. Although oncogenic mutations affecting RAS are common in many other human cancers, tumorigenesis in an important subset of breast cancers is driven instead by increasing activity of wild-type N-Ras. Thus, to fully assess the impact of Ras on tumorigenesis, the role of wild-type as well as mutant Ras proteins must be carefully examined. Citation Format: Ze-Yi Zheng, Wen Bu, Lin Tian, Cheng Fan, Xia Gao, Cuijuan Yu, Liu Jun, Xiaomei Zhang, Yi-Hua Liao, Yi Li, Michael T. Lewis, Dean Edwards, Susan G. Hilsenbeck, Daniel Medina, Thomas P. Zwaka, Charles M. Perou, Chad J. Creighton, Xiang Zhang, Eric C. Chang. Wild type N-Ras, overexpressed in basal-like breast cancer, promotes tumor formation by inducing IL8 secretion via JAK2 activation. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2139. doi:10.1158/1538-7445.AM2015-2139

Impact of breast cancer subtypes and patterns of metastasis on outcome.

Clinical outcome of patients with stage IV breast cancer is dependent on tumor biology, extent, and localization of metastases. Routine imaging diagnostics for distant metastasis is not recommended by the national guidelines for breast cancer follow-up. In this study, we evaluated different patterns of metastases of cancer subtypes in order to generate hypotheses on individualization of follow-up after breast cancer in the adjuvant setting. Patients of the Regional Breast Cancer Center Dresden diagnosed within the years 2006-2011 were classified into the five intrinsic subtypes luminal A (ER+, Her2-, G1/2), luminal B/Her2 negative (ER+, Her2-, G3), triple positive (ER+, PR+, Her2+), Her2-enriched (ER-, Her2+), and triple negative (ER-, PR-, Her2-) and with a median follow-up of 45 months. Tumor stage at time of first diagnosis of breast cancer as well as time and site of metastasis at first diagnosis of distant metastatic disease was analyzed. Tumor specimen of 2284 female patients with primary breast cancer was classified into five subtypes. Distant recurrence-free survival at 3 years was most unfavorable in Her2-enriched (66.8 %), triple negative (75.9 %), and triple-positive breast cancer (81.7 %). The same subtypes most frequently presented with visceral metastases only at first presentation: Her2-enriched 46.9 %, triple negative 45.5 %, and triple-positive breast cancer 37.5 %. Longest median survival of 2.3 years was seen in luminal A and in Her2-enriched metastatic disease, respectively. Median survival was significantly better in the luminal A, Her2-enriched, and triple-positive subtype compared to triple-negative breast cancer (p < 0.005). Differences in time to metastatic disease, first localization of metastases, and overall survival after diagnosis of metastatic disease were shown. Considering new targeted therapies and the option of surgery of oligometastases, screening for visceral metastases might be reasonable after diagnosis of Her2-positive subtypes.

Platinum-based chemotherapy in triple-negative advanced breast cancer.

The purpose of this study was to evaluate the efficacy of platinum-based chemotherapy (PBC) versus conventional non-PBC regimens in a metastatic triple-negative breast cancer (TNBC)setting. We reviewed the electronic patient records of patients with confirmed metastatic TNBC at four major cancer centres in Canada. All patients were allocated into two groups based on type of chemotherapy received (PBC vs. non-PBC) and line of treatment (first-, second-, or third-line). The primary objective of this study was to evaluate the efficacy of PBC in metastatic TNBC in terms of median duration of overall survival (OS) from diagnosis of distant metastatic disease and compare it with the efficacy of conventional non-platinum-based chemotherapy in metastatic TNBC after controlling for known prognostic factors. A total of 153 metastatic TNBC patients were identified, 58 treated with PBC and 95 with non-PBC. The median time in first-line PBC versus non-PBC was not different between the two groups (2 vs. 2 months, p=0.9), the median time on treatment in second and third-line therapy was longer for the PBC group compared to the conventional treated group (4 vs. 1 months, p=0.004; 4 vs. 0.5 months, p=0.004, respectively). Patients who received PBC had a longer OS compared to those managed conventionally (14.5 vs. 10 months, p=0.041). This study evaluates the survival outcomes in a homogenous group of TNBC metastatic patients treated with or without PBC. Our results confirmed our hypothesis of a better OS among PBC-treated TNBC patients compared to conventionally managed TNBC patients. Currently ongoing Phase III trials assessing the benefit of PBC versus other chemotherapeutic regimens in advanced TNBC will help define the role of these agents for the management of this breast cancer subtype.

Survival and Prognostic Factor Analysis of 146 Metastatic Neuroendocrine Tumors of the Mid-Gut

Background: Gastrointestinal neuroendocrine tumors (NETs) are heterogeneous neoplasms that vary in mortality according to location of primary tumor and stage of disease. Past analyses of survival suggest a trend towards improving longevity among patients with metastatic mid-gut NETs. Methods: We evaluated all cases of metastatic NETs of the mid-gut seen in our institution between 1999 and 2003, measuring survival from time of diagnosis of distant metastatic disease. Median and 5-year survival rates were estimated using Kaplan-Meier methodology. We assessed the impact of various prognostic factors including age, gender, hepatic cytoreductive surgery, and operative resection of the primary tumor. Results: 146 cases of metastatic mid-gut NETs were identified. The median overall survival was 103 months and the 5-year survival rate was 75%. Most patients (91%) received octreotide therapy. Other medical treatments included hepatic artery embolization, chemotherapy, and peptide receptor radiotherapy. Primary tumor resection was performed in 69% of cases, and hepatic cytoreductive surgery in 22% of cases. A median survival of 95 months was observed among patients who did not undergo cytoreductive surgery. Operative resection of the primary tumor was not associated with a significant survival advantage. Conclusions: Median overall survival is 103 months (8.5 years) in patients with metastatic mid-gut NETs. Among patients who are not candidates for hepatic cytoreductive surgery, median survival is 95 months (7.9 years). Resection of the primary tumor does not appear to be associated with a survival benefit in the metastatic setting.

Impact of irinotecan and oxaliplatin on overall survival in patients with metastatic colorectal cancer (MCRC): A population- based study

4077 Background: Over the past 10 years, chemotherapeutic options for MCRC has significantly expanded from 5-FU based therapy, to include irinotecan and oxaliplatin. The effect of the availability of these treatments on overall survival is evaluated among patients in 3 time cohorts referred to the British Columbia Cancer Agency (BCCA). Methods: Patients with newly diagnosed or relapsed metastatic colorectal cancer referred to the BCCA in 1995/96, 2000 and 2003/04 were included. In 1995/96, 5-FU was the only palliative chemotherapy agent available at BCCA and irinotecan and oxaliplatin were available in 2000 and 2003, respectively. A one year period was used for the irinotecan cohort to minimize overlap between groups. Overall survival estimates were generated using the Kaplan Meier method. Survival was calculated from time of diagnosis of distant metastatic disease to either death or last contact date. Results: Cohorts were generally similar, however, a significantly higher proportion of patients received chemotherapy in more recent eras ( Table 1 ). Only 25% of patients received both irinotecan and oxaliplatin in 2003/4 and only 10 % received biologic therapies. An improvement in median survival of 3.6 months was observed. The improvement in the treated subgroup was 4.2 months. Outcomes of patients untreated with chemotherapy were unchanged between cohorts. Conclusions: In this population based study, the proportion of patients with MCRC treated with chemotherapy significantly increased between 1995/6 and 2000/2003/4. Patients treated with chemotherapy experienced a 4.2 month increase in median survival in 2003/4 compared to 1995/6. Survival improvements were only significant in the time period when all three effective chemotherapies (5FU, irinotecan and oxaliplatin) were available. As bevacizumab was not available until 2006, its survival impact in this population is not yet known. [Table: see text] No significant financial relationships to disclose.

Does Continuous-Infusion Interleukin-2 Increase Survival in Metastatic Melanoma?

Pharmacy logbooks and clinical trial records were used to identify all 60 patients with metastatic melanoma who were treated as inpatients with intermediate-dose, continuous-infusion interleukin-2 (IL-2) in Hoag Hospital during 1987 to 1998. The hospital tumor registry was used to identify contemporary controls who had not received inpatient IL-2, matched for having distant metastatic melanoma, and by year and stage at original diagnosis, gender, and age. The mean time from original diagnosis to the documentation of distant metastatic disease was similar in both groups, 24 to 26 months. From the date of starting IL-2 therapy, patients had a median survival of 8.8 months, 38% 1-year survival, and 20% 5-year survival, with 8 patients alive beyond 5 years. However, there was no difference in survival from the first date of distant metastatic disease (median 25.8 months for IL-2 versus 31.5 months for controls, with survival rates 5 years after metastatic disease of 26% versus 31%). There was also no difference in overall survival from the date of original diagnosis (60.1 months for the IL-2 group versus 86.3 months for controls, with 5-year survival rates of 51% versus 64%, and 10-year survival rates of 29% versus 33%). This single-institution study failed to establish a survival advantage for patients with metastatic melanoma who received intermediate-dose, continuous-infusion IL-2 administered in the inpatient setting, compared to contemporary, matched-control patients who never received inpatient IL-2 therapy. However, the 5-year survival rates after a diagnosis of distant metastatic disease were a surprisingly high 26% to 31% in both groups. In the absence of a control group, the survival impact of IL-2 has probably been overestimated from single-arm phase II and III trials.