Is surgery indicated for elderly patients with early stage nonsmall cell lung cancer, in the era of stereotactic body radiotherapy?

BACKGROUND: The aim of this article is to assess the influence of comorbidities among elderly patients (at least 70 year old) undergoing surgery for early stage nonsmall cell lung cancer (NSCLC) and to explore the tolerability and efficacy of surgery in relation to stereotactic body radiotherapy (SBRT) in this patient population. METHODS: A review of the literature on the prevalence of comorbidities among elderly patients with early stage NSCLC, and the impact of comorbidity factors on survival following surgery was conducted. Survival rates and the incidence of complications following SBRT for this patient population were also identified. RESULTS: Comorbidities in elderly patients with early stage NSCLC may preclude surgery or lead to poor survival following surgery. However, chronological age alone should not be used as a deciding factor to deny curative treatment in elderly, but fit patients. Stereotactic body radiotherapy is well tolerated by elderly lung cancer patients and may result in survival rates similar to that following surgery. CONCLUSION: SBRT should be the treatment of choice for early stage NSCLC in elderly patients with multiple comorbidities that preclude surgery. The roles of surgery and SBRT for elderly, -fit patients with early stage NSCLC needs to be further defined in future prospective trials.

Cisplatin, cetuximab, and radiation in locally advanced head and neck squamous cell cancer: a retrospective review.

Efficacy of cisplatin versus cetuximab with radiation in locally advanced head and neck cancer (LAHNC) was evaluated. A total of 96 patients with newly diagnosed LAHNC treated at our institution between 2006 and 2011 with concurrent radiation and cisplatin (group A, n = 45), cetuximab (group B, n = 24), or started with cisplatin but switched to cetuximab because of toxicity (group C, n = 27) were reviewed. Chi-square test, analysis of variance, and log-rank test were used for analysis. The three groups had similar baseline characteristics, except for median age, T stage, albumin levels, hemoglobin levels, performance status, and comorbidities. A complete response (CR) was seen in 77%, 17%, and 67% of patients (P < 0.001), respectively. There was no significant difference in median overall survival (OS) between groups A and C. The median OS for groups A and C was not reached (>65 months), even though it was significantly longer than median OS for group B (11.6 months; P ≤ 0.001). The 2-year OS in groups A and C is significantly higher than that in group B (70% for groups A and C, 22% for group B). There is no significant difference in progression-free survival (PFS) between groups A and C. The median PFS for these groups was not reached (>62 months), and is significantly longer than that for group B (4.3 months; P ≤ 0.001). The 2-year PFS of group A (67%) and group C (76%) was significantly longer than that of group B (20%). Cisplatin with radiation appears to be more efficacious even in suboptimal dosing than cetuximab with radiation in LAHNC but the two groups were not well matched.

Feasibility of image-guided radiotherapy and concurrent chemotherapy for locally advanced nonsmall cell lung cancer.

A retrospective review of 32 patients with stage III nonsmall cell lung cancer who underwent chemoradiation with image-guided radiotherapy (IGRT) was recorded. Acute grade 3-4 hematologic and esophageal toxicities developed in 6 and 13 patients respectively. At a median follow-up of 14.5 months, only one patient developed grade 3 pneumonitis. The median survival was estimated to be 17 months. Five patients (15%) developed loco-regional recurrences, and 17 patients (53%) distant metastases. Grade 3-4 toxicities remained significant during chemoradiation with IGRT. However, the reduced rate of severe pneumonitis despite a high tumor dose is encouraging and needs to be investigated in future prospective studies.

Potential applications of imaging and image-guided radiotherapy for brain metastases and glioblastoma to improve patient quality of life.

Treatment of glioblastoma multiforme (GBM) and brain metastasis remains a challenge because of the poor survival and the potential for brain damage following radiation. Despite concurrent chemotherapy and radiation dose escalation, local recurrence remains the predominant pattern of failure in GBM most likely secondary to repopulation of cancer stem cells. Even though radiotherapy is highly effective for local control of radio-resistant tumors such as melanoma and renal cell cancer, systemic disease progression is the cause of death in most patients with brain metastasis. Preservation of quality of life (QOL) of cancer survivors is the main issue for patients with brain metastasis. Image-guided radiotherapy (IGRT) by virtue of precise radiation dose delivery may reduce treatment time of patients with GBM without excessive toxicity and potentially improve neurocognitive function with preservation of local control in patients with brain metastasis. Future prospective trials for primary brain tumors or brain metastasis should include IGRT to assess its efficacy to improve patient QOL.

Image-guided radiotherapy for locally advanced head and neck cancer.

Treatment of locally advanced head and neck cancer remains a challenge because of the head and neck complex anatomy and the tumor invasion to the adjacent organs and/or metastases to the cervical nodes. Postoperative irradiation or concurrent chemoradiation may lead to damage of radiosensitive structures such as the salivary glands, mandible, cochlea, larynx, and pharyngeal muscles. Xerostomia, osteoradionecrosis, deafness, hoarseness of the voice, dysphagia, and aspiration remain serious complications of head and neck irradiation and impair patient quality of life. Intensity-modulated and image-guided radiotherapy by virtue of steep dose gradient and daily imaging may allow for decreased radiation of the organs at risk for complication while preserving loco-regional control.

Outcome for patients with triple-negative breast cancer is not dependent on race/ethnicity.

Introduction. Triple negative breast cancer (TNBC) is biologically aggressive and is associated with a worse prognosis. To understand the impact of race/ethnicity on outcome for patients with TNBC, confounding factors such as socioeconomic status (SES) need to be controlled. We examined the impact of race/ethnicity on a cohort of patients of low SES who have TNBC. Methods. 786 patients with Stage 0-III breast cancer were evaluated. Of these, 202 patients had TNBC (26%). Primary endpoints were cancer recurrence and death. ZIP code-based income tract and institutional financial data were used to assess SES. Data were analyzed using Kaplan-Meier survival analysis, log-rank tests, Cox Proportional hazard regression, chi square test, and t-tests. A P value ≤0.05 was considered statistically significant. Results. Of the 468 African-Americans (60%) in the database, 138 had TNBC; 64 of 318 Caucasians had TNBC. 80% of patients had an annual income of ≤$20,000. The 5-year overall survival was 77% for African-American women versus 72% for Caucasian women (P = 0.95). On multivariate analysis, race/ethnicity had an impact on disease-free survival (P = 0.027) but not on overall survival (P = 0.98). Conclusion. In a predominantly indigent population, race/ethnicity had no impact on overall survival for patients with triple negative breast cancer.

Should a routine metastatic workup be performed for all patients with pathologic N2/N3 breast cancer?

BACKGROUND: Node-positive breast cancer patients are at risk for metastatic disease. A routine metastatic workup might or might not be necessary for all patients with N2 or N3 diseases. The National Comprehensive Cancer Network guidelines recommend a metastatic workup for patients with T3N1 disease, yet no definitive recommendations are made for N2/N3 diseases. We hypothesized that for patients with operable pathologic N2/N3 diseases, a metastatic workup should only be considered for patients with T3/T4 lesions. STUDY DESIGN: Two hundred and fifty-six patients with pathologic N2/N3 diseases were identified from a prospective breast cancer database of 1,329 patients with stage 0 to III breast cancer. A metastatic workup included chest x-rays, bone scans, CT scans, and PET scans. Primary end point was incidence of stage IV disease at the time of diagnosis or within 1 month of definitive surgery. Statistical analysis included chi-square test, independent t-test, Kaplan-Meier Survival method, log-rank test, and Cox proportional hazard model. A p value ≤ 0.05 was considered statistically significant. RESULTS: There were 158 patients with N2 disease (62%) and 98 with N3 disease (38%). Overall, 16% had stage IV disease (N2 = 15%, N3 = 16%). There was no significant difference in age (p = 0.37), tumor size (p = 0.89), tumor grade (p = 0.09), estrogen-receptor status (p = 0.23), or progesterone-receptor status (p = 0.35) between the N2 and N3 groups. Incidences of stage IV disease were T0/T1, 0%; T2, 6%; T3, 22%; and T4, 36%. Multivariate analysis demonstrated that only T stage (p = 0.0006) and grade (p = 0.026) were independent predictors of overall survival. CONCLUSIONS: A metastatic workup is only indicated for N2/N3 patients with T3 or T4 primary lesions.

Comorbid predictors of poor response to chemoradiotherapy for laryngeal squamous cell carcinoma.

OBJECTIVES/HYPOTHESIS: To investigate whether a correlation exists between medical comorbidities and disease control following primary therapy of laryngeal squamous cell carcinoma. STUDY DESIGN: Retrospective medical record review. METHODS: A retrospective chart review was performed on patients diagnosed with laryngeal carcinoma between 1997 and 2011. The Adult Comorbidity Evaluation 27 (ACE 27) index was used to evaluate severity of comorbid health. Ten-year disease-free survival rates and median disease-free intervals were calculated, and significant associations between disease recurrence and comorbid factors were determined using the log-rank test. Independent significant risk factors for disease recurrence were determined with the Cox proportional hazard regression model. RESULTS: Of the 181 patients identified, 121 were treated nonsurgically with either primary radiotherapy (XRT) (49%) or chemoradiotherapy (CRT) (51%). Sixty patients (50%) experienced recurrence of their disease. The 10-year disease-free survival rate was 23.8%, and the median disease-free survival was 58 months (95% confidence interval, 12-108 months). Factors observed to be significantly associated with recurrence within 10 years after treatment were renal disease (P < .01), pulmonary disease (P < .01), malnutrition (P < .01), T size (P < .01), stage (P = .02), and ACE 27 Index (P < .01). Independent significant risk factors for recurrence were malnutrition (P < .01), T stage (P = .01), and ACE 27 (P < .01). Adjusted hazard ratios were 1.43 for T stage, 2.58 for ACE 27, and 2.15 for malnutrition. CONCLUSIONS: The results of this study demonstrate that there is a significant association between increased comorbidity and recurrent disease in laryngeal carcinoma treated with XRT/CRT. The consideration of comorbid health in primary treatment planning may improve the success and survival of patients with laryngeal squamous cell carcinoma.

Trimodal therapy for inflammatory breast cancer: a surgeon's perspective.

Inflammatory breast cancer (IBC) is a rare and most aggressive form of breast cancer. The onset and progression of disease are rapid; diagnosis must be made expediently to initiate treatment quickly. In this review, the clinical presentation, trimodal therapy, surgical principles and a brief summary of the Louisiana State University at Shreveport experience with IBC are presented. With this aggressive approach, 5-year survival of better than 40-50% can be expected. This represents a substantive improvement in clinical outcome for IBC patients compared with 30 years ago.

Is breast conservation therapy a viable option for patients with triple-receptor negative breast cancer?

BACKGROUND: Triple-receptor negative breast cancers (TNBC) are aggressive neoplasms that lack estrogen-receptor, progesterone-receptor, and HER-2 expressions. Comparative analysis of breast conservation therapy (BCT) versus mastectomy for TNBC is reported sparsely. We hypothesized that, despite its aggressive behavior, TNBC can be managed with BCT. METHODS: Outcomes for 202 patients with TNBC who were treated with BCT or mastectomy were analyzed. Primary endpoints were cancer recurrence and death. Statistical analysis performed included Kaplan-Meier survival analysis, log-rank, independent samples t test, Cox proportional hazard model, and Chi-square. RESULTS: BCT was performed in 30% of patients. Isolated local recurrence rate for BCT and mastectomy was 0% and 10.6%, respectively (P = .02). Isolated regional recurrence rate for BCT and mastectomy was 1.6% and 1.4%, respectively (P = .61). Neither concomitant locoregional and distant recurrence rate (P = .73) nor isolated distant recurrence rate (P = .71) was significantly different between the BCT and mastectomy groups. The 5-year overall survival (OS) was better for the BCT group than the mastectomy group (89% vs 69%; P = .018); however, this was likely due to the mastectomy group having a larger neoplasm size (T3/T4: 4% BCT vs 27% mastectomy; P = .0002), advanced N-disease (N2/3: 8% BCT vs 25% mastectomy; P = .0003), and advanced stage of disease (stage 3: 8% BCT vs 35% mastectomy; P < .0001). On multivariate analysis, surgical approach had no effect on either disease-free survival (P = .60) or OS (P = .19); only t-stage was an independent predictor of disease-free survival (P = .02), while N-stage was an independent predictor for OS (P = .03). CONCLUSION: Despite TNBC's aggressive behavior, breast conservation therapy is a viable option for selected patients with TNBC.

N2 disease in patients with head and neck squamous cell cancer treated with chemoradiotherapy: is there a role for posttreatment neck dissection?

OBJECTIVES: To determine whether nodal necrosis and node size of 3 cm or larger are risk factors for recurrent neck disease and whether negative computed tomography-positron emission tomography (CT-PET) results 8 weeks or more after therapy indicate complete response in the neck in patients with N2 disease. DESIGN: Retrospective study. SETTING: State university hospital. PATIENTS: Fifty-six patients with head and neck squamous cell cancer and N2 disease treated with chemoradiotherapy were evaluated for persistent or recurrent neck disease. Tumor characteristics analyzed were primary site, T category, nodal size (<3 cm or > or =3 cm), nodal necrosis based on hypodensity of one-third or more of the node, and type of N2 disease (N2a, N2b, or N2c). Forty-eight of the 56 patients underwent CT-PET to determine treatment response after chemoradiotherapy. Clinical examination, imaging, and pathologic specimens were used to confirm disease recurrence. MAIN OUTCOME MEASURES: The number of recurrence events, disease-free interval, and positive posttreatment CT-PET result in the neck. RESULTS: Most patients had oropharyngeal tumors (n = 37; 66%), T2 tumors (n = 21; 38%), nodes 3 cm or larger (n = 43; 77%), positive necrosis (n = 40; 71%), and N2c disease (n = 28; 50%). Multivariate analysis determined that no factors were significant predictors of recurrence, except for positive posttreatment PET results (P < .001). Comparison of CT-PET with nodal recurrence demonstrated a sensitivity of 82%, a specificity of 97%, a negative predictive value of 95%, and a positive predictive value of 90%. CONCLUSION: Posttreatment neck dissections may not be indicated for patients with N2 disease and a negative CT-PET result, even in patients with nodal necrosis and nodes 3 cm or larger.

Overexpression of CXCR4 in primary tumor of patients with HER-2 negative breast cancer was predictive of a poor disease-free survival: a validation study.

BACKGROUND: Although HER-2 negative tumors are thought to be less aggressive than their counterpart, there is a subset that behaves poorly. The molecular mechanism to account for this is unknown. The chemokine receptor CXCR4 is often upregulated in a wide array of cancers. Using a training dataset, we previously reported that high CXCR4 overexpression portends a poor outcome among patients with HER-2 negative breast tumors. This study aims to validate these findings, using our validation dataset. METHODS: There were 115 patients with stages I-III, HER-2 negative breast cancers who were prospectively accrued and analyzed. CXCR4 levels from primary tumors were detected using Western blots, and results were quantified against 1 microg of HeLa cells. CXCR4 expression was defined as low (<6.6 fold) or high (> or =6.6 fold). Primary endpoint was cancer recurrence. Statistical analysis performed included Spearman correlation, Fisher exact test, Kaplan-Meier survival analysis, Cox proportional hazard ratio model, and log-rank test. RESULTS: There were 13 patients in the high (> or =6.6 fold) and 102 patients in the low CXCR4 group (<6.6 fold). Overall survival (OS) and disease-free survival (DFS) for the cohort was 84 and 71%, respectively. The 5-year OS for the high CXCR4 group was 52% and for the low CXCR4 group was 86% (P = 0.08). The 5-year DFS for the high CXCR4 and low CXCR4 group was 38 and 74%, respectively (P = 0.01). CONCLUSION: We validated that high CXCR4 overexpression in primary tumors of patients with HER-2 negative tumors portend a poor outcome. These findings should be confirmed with either a prospective clinical trial and/or an external validation study.

Return of vocal cord movement: an independent predictor of response to nonsurgical management of laryngeal cancers.

OBJECTIVE: To determine whether return of vocal cord function after treatment of T2b/T3 laryngeal carcinoma is an independent prognostic factor for locoregional recurrence. STUDY DESIGN: A retrospective review of patients treated with radiation +/- chemotherapy between 2000 and 2005 for T2 with vocal cord paresis and T3 laryngeal carcinoma was conducted. METHODS: Only those patients obtained from the tumor registry with pre-and posttreatment video stroboscopies were included. Patients' charts were reviewed for local and regional recurrence after treatment. Fisher's exact test was used to determine significant association between recurrence and possible risk factors. RESULTS: Fourteen patients met the inclusion criterion. Six patients had T2 lesions with vocal cord paresis, and eight patients had T3 lesions. Fifty percent of patients with T2 and 75% of patients with T3 lesions had return of vocal cord function after treatment. Five of 14 patients did not have return of vocal cord function, and of these, 100% had locoregional recurrence. Of the nine patients who had return of vocal cord movement, none of the patients had recurrence. The proportion of recurrence was significantly higher for those whose vocal function did not return compared with the patients whose vocal function returned (100% vs. 0%, P < .01). CONCLUSION: The immobile vocal cord is associated with a worse prognosis and is therefore factored into the American Joint Commission on Cancer staging for laryngeal tumors. We show that vocal cord immobility is an independent prognostic factor of recurrence even after treatment and can predict treatment failure in T2 and T3 lesions of the larynx.

The role of whole-body fluorine-18-FDG positron emission tomography in the detection of recurrence in symptomatic patients with stages II and III breast cancer.

BACKGROUND: The role of whole-body fluorine-18-FDG positron emission tomography (FDG-PET) as an adjunct localize recurrence in stages II and III breast cancer patients who present with clinical suspicion for recurrence is not well established. We report our experience in such a patient population. METHODS: A retrospective review of all patients with stages II and III breast cancer who had a whole-body FDG-PET scan was performed. RESULTS: Of the 23 patients who fit the criteria, 9 had stage II and 14 had stage III breast cancer. Overall sensitivity, specificity, and accuracy were 81%, 100%, and 87%, respectively. Positive and negative predictive values for stages II and III were 100% and 83%, respectively, and 100% and 50%, respectively. FDG-PET detected two recurrences that were missed by conventional imagings, but such recurrences were local and amenable for biopsy. CONCLUSIONS: In patients with stages II and III breast cancer who present with a suspicion for recurrent disease, a whole-body FDG-PET scan may be a useful adjunct in the evaluation of recurrence. However, its added benefit over conventional imaging should be questioned.

Neoadjuvant chemotherapy in stage III breast cancer.

Neoadjuvant chemotherapy in advanced breast cancer can potentially downstage disease prior to definitive surgery. In this study, a doxorubicin-based neoadjuvant regimen was administered to stage III breast cancer patients to assess 1) primary tumor response, 2) tumor involvement of resection margins, and 3) predictive value in cancer outcome. Eighty-two patients with stage IIIA and IIIB breast cancer diagnosed between 1990 and 2003 were studied. All patients received similar chemotherapy regimens, consisting of doxorubicin, cisplatin, and 5-fluorouracil, plus surgery and radiation therapy. End points measured include primary tumor response [complete response (CR) = 100%, partial response (PR) > 50%, or no response (NR) < or = 50%], resection margins for tumor, disease-free, and overall survival. Kaplan-Meier and log-rank tests were performed. Of the 82 patients studied, 34 received neoadjuvant therapy, 48 received conventional postoperative treatment. Seventy-two per cent of the stage IIIB and 22 per cent of the stage IIIA patients received neoadjuvant therapy. In the neoadjuvant group, 29 (85%) patients demonstrated tumor response, 9 (26%) of which were CR. Tumor-free resection margins were achieved in 94 per cent of the neoadjuvant group. Survival analysis demonstrated no benefit comparing neoadjuvant versus postoperative adjuvant therapy but hints at improved disease-free survival in neoadjuvant CR patients (log-rank test, P = 0.07). Eighty-five per cent of patients with stage III breast cancer treated with neoadjuvant chemotherapy experienced clinical response, with 26 per cent CR, and 97 per cent tumor-free resection margins. CR may portend a better cancer outcome.

NS 398 radiosensitizes an HNSCC cell line by possibly inhibiting radiation-induced expression of COX-2.

PURPOSE: Cyclooxygenase-2 (COX-2) protein is frequently elevated in squamous cell carcinoma of the head and neck (HNSCC). The aim of this study was to determine if COX-2 inhibitors have radiosensitizing effects in HNSCC and understand the mechanism by which this occurs. MATERIALS AND METHODS: The radiosensitizing effects of a selective COX-2 inhibitor, NS398, on a HNSCC cell line HEp3, were determined using clonogenic survival assay. Cells were pretreated with the dose of NS398 at which 50% growth inhibition occurred (IC(50)) and then irradiated. COX-2 protein and mRNA were then determined in the presence and absence of NS398. RESULTS: NS398 significantly decreased (p < 0.0001) the calculated survival fraction (SF) for all radiation doses (0.79 to 0.41 at 2 Gy). A significant increase in COX-2 protein of 2.8 fold for 2 Gy and 3.5 fold for 6 Gy was noted 48 h after radiation. Interestingly, the upregulation of COX-2 protein with radiation was suppressed when cells were pretreated with NS398. Quantitative reverse transcriptase polymerase chain reaction showed no significant corresponding increase in COX-2 mRNA at 48 h with ionizing radiation. CONCLUSIONS: The radiosensitizing effect of NS398 could be due to inhibition of radiation-induced COX-2 upregulation by this drug. NS398, known as an inhibitor of COX-2 enzyme activity, down-regulated COX-2 protein expression, which may indicate that NS398 can act upstream of COX-2, and this change appears to be post-transcriptional.