Outcome following radiotherapy for loco-regionally recurrent non-small cell lung cancer

Local and regional recurrence of non-small cell lung cancer is reported to occur in 13–20% of treatment failures after resection. Reported post-recurrent median survival following radiotherapy ranges from 9 to 14 months. This study examines survival following radiotherapy alone for patients with loco-regionally recurring non-small cell lung cancer after initial surgery. Fifty-five patients, receiving radiotherapy at Westmead Hospital between 1979 and 1997, were eligible for study. Data were collected retrospectively by reviewing patient records. The end-point was overall survival. Symptom control was also recorded. Prognostic factors for analysis included age, sex, original presenting stage, disease-free interval (DFI), performance status, site of recurrence, treatment intent and dose. The median overall survival was 11.5 months (95% confidence interval: 8.1–13.0). Survival following treatment with radical intent was 26 months compared to 10.5 months for patients treated with palliative intent (P = 0.025). There was no significant difference in survival for short (≤2 years) or long DFI, performance status, radiation dose, age, sex, site of recurrence or stage. Most patients (55%) had partial or complete resolution of symptoms. Radiotherapy results in overall post-recurrence median survival of nearly 1 year, consistent with previous published data. Radical treatment intent predicts better prognosis as a result of patient selection and higher dose. Radiotherapy is effective at palliating symptoms of this disease.     

Factors associated with actual long-term survival following soft tissue sarcoma pulmonary metastasectomy

Aims

To identify clinicopathologic and treatment variables associated with long-term overall survival (OS) in soft tissue sarcoma (STS) patients with lung metastases undergoing pulmonary metastasectomy (PM).

Methods

Retrospective review of 94 STS PM patients with an actual follow-up ≥5 years. Data were collected on demographics, tumor features, treatment, and outcome.

Results

Most primary tumors were intermediate/high grade and the common histopathologies were evenly distributed. Half of the primary tumors were located on the extremities. The mean disease-free interval (DFI) from time of original diagnosis until metastases was 25 months (median 15 months). Eighteen patients had synchronous metastatic disease. Bilateral pulmonary metastases and >1 metastasis were common. The median number of metastases resected was 2.5. Thirty-four patients had extrapulmonary tumor at the time of PM; all extrapulmonary disease was resected. Negative margin resection (R0) PM was performed in 74 patients. Actual 5-year disease-free survival (DFS) and OS for all patients were 5% and 15%, respectively. For the R0 group, actual 5-year DFS and OS were 7% and 18%, respectively. R0 resection and a prolonged DFI were associated with improved OS. Patient characteristics, tumor features, local recurrence, and adjuvant therapy did not affect OS.

Conclusions

Less than 20% of STS PM patients will survive 5 years. Complete resection and DFI are the most predictive factors for prolonged survival.     

Disease-free survival after resection of lung metastases in patients with breast cancer.

AIMS: Metastatic breast cancer is a systemic disease. The discussion concerning the resection of lung metastases in patients with breast cancer is controversial. METHODS: Retrospective analysis of 25 patients with suspected pulmonary metastases operated between March 1989 and September 1998. Survival probabilities and disease-free survival was analysed using the Kaplan-Meier method and the log-rank test. RESULTS: The median survival rate after resection of lung metastases for the 21 patients was 96.9 months. The disease-free survival (DFS) after resection of lung metastases was 27.6 months. Survival was not influenced by the receptor status, lymph node involvement, number of lung metastases (p=0.8) or the disease-free interval (DFI) (0.59). DFS was, however, influenced by the DFI. With a DFI of <2 years survival was 8.5 months, whereas with a DFI >2 years it was 36.1 months (p=0.012). The DFS was influenced, but not statistically significant, by the number of lung metastases (n=1/n>1). The median DFS was 28.8 months with one metastasis and 13.1 months with multiple metastases (p=0.29). CONCLUSIONS: The indication to remove solitary lung metastases in patients with previous breast cancer is supported by these findings. Especially when the disease-free interval is greater than two years.     

Results and prognostic factors of surgery in the management of non-small cell lung cancer with solitary brain metastasis.

Between 1975 and 1988, 37 patients with resectable non-small cell lung cancer (NSCLC) and synchronous (within 1 month, n = 10) or metachronous (n = 27) solitary brain metastasis (SBM) underwent combined excision of their lesions. Overall 5-year and median survival were 30% and 27 months (range, 3 to 125+ months), respectively. Twenty-seven patients had a relapse, and their median disease-free interval (DFI) was 17.5 months (range, 1 to 108 months). The most frequent (78%, n = 20) site of first recurrence locally was either the ipsilateral thorax (n = 14) or brain (n = 6). In univariate analysis, age, primary tumor and lymph node status; tumor histology, size, and side; type of pulmonary resection; side and location of SBM; and onset of presentation did not affect survival and DFI. By contrast, the interval (less than or equal to versus greater than 12 months) between the two operations significantly affected survival (P = 0.0096) and DFI (P = 0.046). The DFI was also affected by the administration of adjuvant chemotherapy (AC) for the primary tumor (P = 0.02). Using the Cox model, AC was the most independent predictor of DFI. These data support the inclusion of surgery in the therapeutic armamentarium for patients with NSCLC and SBM.     

Results of surgical treatment of pulmonary metastases

From 1970 to 1993, 155 thoracotomies for metastatic lung tumors were performed on 113 patients in the Department of Surgery, Kanazawa University School of Medicine. Overall 30-day mortality amounted to 0.9% (1/113). The cumulative 3- and 5-year survival rates were 39.4% and 29.1%, respectively. The overall median survival was 24 months. The 5-year survival rate for carcinoma was 37.2% and for sarcoma it was 14.5% (P < 0.01). The other significant predictors of better long-term survival with metastatic lung tumors were solitary lesions, disease-free interval (DFI) > 24 months, and tumor size ≤ 20 mm in diameter. There was no significant difference in survival based on the method of pulmonary resection. Repeat thoracotomy for recurrent metastases was performed in 27 patients, whose 5-year survival rate after the first lung resection was 35.5%. For bilateral pulmonary metastases, we recently performed simultaneous bilateral thoracotomy via median sternotomy on 25 patients and transsternal simultaneous bilateral thoracotomy on 8 patients. The latter procedure provides a wide operative field and better survival. We conclude that resection of metastatic lung tumors is safe and effective, and that repeat thoracotomy is warranted in selected patients with recurrent pulmonary metastases. © 1995 Wiley-Liss, Inc.     

Lymphatic invasion is a prognostic factor for bladder cancer treated with radical cystectomy

Background We aimed to elucidate the significance of pathological prognostic factors in patients with bladder cancer treated with radical cystectomy and pelvic lymphadenectomy focusing on the association between lymphatic invasion and disease recurrence. Methods Ninety-one patients with ladder cancer who had undergone radical cystectomy were examined retrospectively. Clinicopathological findings and clinical outcomes were analyzed. Patients who received palliative cystectomy or neoadjuvant chemotherapy and patients who did not receive lymphadenectomy owing to a poor general condition or far advanced local disease status were excluded. Results Lymphatic invasion and lymph node involvement were present in 45.1% and 23.1% of patients, respectively. Multivariate analyses, using the Cox proportional hazards model, indicated that lymphatic invasion (hazard ratio [HR], 5.30; P = 0.007) and lymph node involvement (HR = 3.05; P = 0.016) were independent prognostic factors for disease-specific survival. Of the 91 patients, 29 (31.9%) had recurrent disease during the follow-up period. The rate of recurrence in patients with lymphatic invasion and without lymph node involvement was 50% (11/22), which was not significantly different from that in patients with both lymphatic invasion and lymph node involvement (73.7%; 14/19; P = 0.121), indicating a high risk of disease recurrence in patients with bladder cancer with lymphatic invasion even in the absence of the lymph node involvement. Conclusion In patients with bladder cancer treated with radical cystectomy, lymphatic invasion is an independent prognostic factor for disease-specific and disease-free survival. Patients with lymphatic invasion have a high risk of disease recurrence after radical cystectomy even in the absence of lymph node involvement.     

Resection of recurrent pulmonary metastases in patients with osteosarcoma

BACKGROUND: Surgical resection of lung metastases is widely accepted in osteosarcoma patients. Few data exist on treatment of recurrent pulmonary metastases. The authors of the current study retrospectively analyzed patients with osteosarcoma who received surgery for recurrent lung metastases. METHODS: From 1980 to 2001, 127 metastasectomies were performed on 94 patients. Criteria of eligibility were no metastases beyond the lung, no local recurrence, possibility of achieving complete resection of metastases without causing respiratory insufficiency, acceptable operative risk. Data were statistically elaborated with survival analysis according to Kaplan-Meier method of univariate analysis, life tables and Gehan statistic model, and multivariate analysis using Cox regression test. Results were considered in terms of time from first (DFI1) and second (DFI2) metastasectomy. RESULTS: Of 94 patients operated upon twice, 59 (62.7%) died. Thirty-five (37.3%) are alive; 31 (32.9%) of these are continuously disease-free. The 3- and 5-year event-free actuarial survival curve from first metastasectomy was 45%, and 38%, respectively, whereas from the second metastasectomy, it was 33% and 32%, respectively. According to a Cox regression model, DFI1 has a risk of death of 0.974 times and DFI2 of 0.972 times for every additional month of survival. In multivariate analysis, Cox regression test showed the best predictive model of local recurrence and number of metastases (P = 0.0014). CONCLUSIONS: The authors concluded that patients persistently free of the primary osteosarcoma who developed recurrent resectable metastatic disease of the lung should be considered for reoperation a second, third, or fourth time, as these patients had similar DFI curves after five-years.     

Clinical features and prognostic factors for extracranial oligometastatic breast cancer in China

Evidence of an oligometastatic state in metastatic breast cancer (MBC) is relatively limited. The aim of our study was to investigate the clinical features and prognostic factors for extracranial oligometastatic breast cancer and to identify the best treatment approaches in this select population. Fifty postoperative inpatients diagnosed with extracranial oligometastatic breast cancer at the National Cancer Center in China between 2009 and 2014 were consecutively enrolled. Oligometastatic breast cancer was defined as MBC with three or fewer metastatic lesions confined to one organ; de novo Stage IV disease and local-regional recurrence were excluded. The median progression-free survival (PFS) and overall survival (OS) times were 15.2 and 78.9 months, respectively, and the 2-year PFS and 5-year OS rates were 40% and 58%, respectively. First-line treatment approach with standard systemic treatment + surgical resection for all metastatic lesions was an independent prognostic factor for prolonged PFS (hazard ratio = 0.32; 95% confidence interval [CI], 0.14-0.73; P = .006) and OS (hazard ratio = 0.35; 95% CI, 0.14-0.86; P = .022). Subgroup analysis showed that patients with a disease-free interval (DFI) ≥24 months, one metastatic lesion or the hormone receptor (HR) + subtype were more likely to get benefit from resection. Patients with oligometastatic breast cancer have a relatively good prognosis. Surgical resection for metastatic lesions could significantly improve PFS and OS. Further prospective research is warranted to confirm the results and to develop biomarkers for better patient selection.     

Is Cure Possible After Sequential Resection of Hepatic and Pulmonary Metastases From Colorectal Cancer?

Background

Surgical resection is an established therapeutic strategy for colorectal cancer (CRC) metastasis. However, controversies exist when CRC liver and lung metastases (CLLMs) are found concomitantly or when recurrence develops after either liver or lung resection. No predictive score model is available to risk stratify these patients in preparation for surgery, and cure has not yet been reported.

Long-term evaluation of intrapleural bacillus Calmette-Guerin with or without adjuvant chemotherapy in completely resected stages II and III non-small-cell lung cancer.

Between January 1979 and December 1980, 52 patients with completely resected stages II and III non-small-cell lung cancer (NSCLC) were randomly assigned to receive either adjuvant chemotherapy (cyclophosphamide, doxorubicin, and vincristine--CAV) plus intrapleural bacillus Calmette-Guerin (BCG) (n = 26) or adjuvant CAV alone (n = 26). Careful intraoperative staging was performed in all patients, and stratification for histology (squamous versus nonsquamous) and stage (II or III) ensured a balanced randomization for these factors. With a median follow-up time of 111 months, overall 10-year and median survival were 21% and 20 months (range 2-127 + months), respectively. Thirty-four (95%) patients relapsed in extrathoracic sites, and five (5%) developed loco-regional recurrence; their overall median disease-free interval (DFI) was 10 months (range 1-73 months). There was a 9% and 2.5 month difference in survival (p = .76) and disease-free interval (p = .67), respectively, favoring the BCG arm. There were no significant differences in the sites and patterns of first recurrence comparing the two treatment arms. In conclusion, there is no suggestion of a significant therapeutic advantage from intrapleural BCG in conjunction with adjuvant chemotherapy for completely resected stages II and III NSCLC.     

Prognostic factors for recurrent breast cancer patients with an isolated,limited number of lung metastases and implications for pulmonary metastasectomy

BACKGROUND:

The aim of this study was to evaluate the clinical treatment outcomes of recurrent breast cancer with a limited number of isolated lung metastases, and to evaluate the role of pulmonary metastasectomy.

METHODS:

The authors consecutively enrolled 140 recurrent breast cancer patients with isolated lung metastasis from 1997 to 2007 in Seoul National University Hospital and retrospectively analyzed 45 patients who had <4 metastatic lesions.

RESULTS:

Fifteen patients had pulmonary metastasectomy followed by systemic treatment (pulmonary metastasectomy group), and 30 received systemic treatment alone (nonpulmonary metastasectomy group). The 3‐year progression‐free survival (PFS) and 4‐year overall survival (OS) was significantly longer in the pulmonary metastasectomy group than in the nonpulmonary metastasectomy group (3‐year PFS, 55.0% vs 4.5%, P < .001; 4‐year OS, 82.1% vs 31.6%, P = .001). In multivariate analysis, a disease‐free interval (DFI) of <24 months (hazard ratio [HR], 4.53; 95% CI, 1.72‐11.90), no pulmonary metastasectomy (HR, 9.52; 95% CI, 3.34‐27.18) and biologic subtypes such as human epithelial growth factor receptor‐2 positive (HR, 3.00; 95% CI, 1.04‐8.64) and triple negative (HR, 3.92; 95% CI, 1.32‐11.59) were independent prognostic factors for shorter PFS.

CONCLUSIONS:

The authors' results demonstrated that DFI and biologic subtypes of tumor are firm, independent, prognostic factors for survival, and pulmonary metastasectomy can be a reasonable treatment option in this population. Further prospective studies are warranted to evaluate the role of pulmonary metastasectomy. Cancer 2010. © 2010 American Cancer Society.     

Secondary cytoreductive surgery for recurrent epithelial ovarian carcinoma: proposal for patients selection

The value of secondary cytoreductive surgery (SCS) for recurrent ovarian cancer is still controversial. The aim of this study was to clarify candidates for SCS. Between January 1987 and September 2000, we performed SCS in 44 patients with recurrent ovarian cancer, according to our selection criteria, disease-free interval (DFI) >6 months, performance status <3, no apparent multiple diseases, age <75 years and no progressive disease during preoperative chemotherapy, if undertaken. The variables were investigated by univariate and multivariate analyses. Of 44 patients, 26 (59.1%) achieved complete removal of all visible tumours at SCS. Secondary cytoreductive surgery outcome, complete or incomplete resection, was significantly related to overall survival (P=0.0019). As for variables determined before SCS, DFI >12 months, no liver metastasis, solitary tumour and tumour size <6 cm were independently associated with favourable overall survival after recurrence in the multivariate analysis. Patients with three or all four variables (n=31) had significantly better survival compared with the other patients (n=13) (47 vs 20 months in median survival, P<0.0001). In these patients, fairly good median survival (40 months) was obtained even in patients with incomplete resection. Secondary cytoreductive surgery had a large impact on survival of patients with recurrent ovarian cancer when they had three or all of the above-mentioned four factors at recurrence. These patients should be considered as ideal candidates for SCS.     

Carcinoma of the lung: Immunotherapy with intradermal BCG and allogeneic tumor cells

After lobectomy or pneumonectomy 45 patients with stage I and 6 with stage II non-small cell carcinoma of the lung were randomized to receive: no further therapy; intradermal BCG; or BCG plus allogeneic irradiated tumor cells intra-dermally twice monthly for 24 months. Patients were observed for 2–51 months at this writing. The homogeneity of the disease free interval (DFI) (i.e., differences in the pattern of relapses) was tested for the three groups. Analysis indicated signifance at the p?0.062 level comparing DFI from control to BCG treated patients to BCG + cells treated patients; a difference also was found when the control group was compared with the combined immunotherapy treated groups (p = 0.061). When only patients with stage I disease were analyzed by trend analysis this difference was magnified in favor of the immunotherapy treated patients (p = 0.027); analysis of the T₁NoMo only groups revealed a similar result (p = 0.042). No significant differences were seen when data were analyzed for survival. Moderately severe local inflammatory reactions occurred in 43% of patients who received BCG immunotherapy, requiring reduction in frequency of its administration. There were no adverse effects from the administration of allogeneic tumor cells. Pasteur BCC may prolong DFI in resectable lung cancer and warrants further investigation in clinical trials.     

MUC4 expression correlates with poor prognosis in small-sized lung adenocarcinoma

The mortality of lung cancer remains high, despite improved diagnostic techniques that allow small lung tumors to be detected. In this study, we evaluated the prognostic significance of the tracheal mucin MUC4 by immunohistochemical investigation of the expression profiles of MUC4, ErbB2, p27 and MUC1 in lung adenocarcinoma specimens (non-bronchiolo-alveolar type, < or =3cm) from 185 patients. MUC4 is a membrane mucin, similarly to MUC1, and in addition MUC4 functions as an intra-membrane ligand for receptor tyrosine kinase ErbB2 and is associated with regulation of p27. However, MUC4 expression was found to be unrelated to expression of MUC1, ErbB2 and p27 in small-sized lung adenocarcinomas. The disease-free interval (DFI) and survival rate of 25 patients with high MUC4 expression (> or =25% of neoplastic cells stained) were significantly lower than those of 160 patients with low MUC4 expression (<25% of neoplastic cells stained) (P<0.05), whereas ErbB2 and p27 expression showed no significant correlation with DFI and survival. Univariate analysis showed that high MUC4 and p27 expression correlated with blood vessel invasion (P=0.0004), and MUC4 expression was frequently detected in regions of stromal invasion. In addition, the survival rate of stage IA patients with high MUC4 expression was significantly lower than that of stage IA patients with low MUC4 expression (P<0.05). In conclusion, high MUC4 expression in small-sized lung adenocarcinomas correlates with a short DFI and a poor survival rate. Therefore, MUC4 expression might be a new independent factor for prediction of outcome and indication of poor prognosis in lung adenocarcinoma.     

Platinum/taxane‐based chemotherapy with or without radiation therapy favorably impacts survival outcomes in stage I uterine papillary serous carcinoma

BACKGROUND:

A study was undertaken to determine recurrence patterns and survival outcomes of stage I uterine papillary serous carcinoma (UPSC) patients.

METHODS:

A retrospective, multi‐institutional study of stage I UPSC patients diagnosed from 1993 to 2006 was performed. Patients underwent comprehensive surgical staging; postoperative treatment included observation (OBS); radiotherapy alone (RT); or platinum/taxane–based chemotherapy (CT) ± RT.

RESULTS:

The authors identified 142 patients with a median follow‐up of 37 months (range, 7‐144 months). Thirty‐three patients were observed, 20 received RT alone, and 89 received CT ± RT. Twenty‐five recurrences (17.6%) were diagnosed, and 60% were extrapelvic. Chemotherapy‐treated patients experienced significantly fewer recurrences than those treated without chemotherapy (P = .013). Specifically, CT ± RT patients had a lower risk of recurrence (11.2%) compared with patients who received RT alone (25%, P = .146) or OBS (30.3%, P = .016). This effect was most pronounced in stage IB/IC (P = .007). CT‐ and CT + RT–treated patients experienced similar recurrence. After multivariate analysis, treatment with chemotherapy was associated with a decreased risk of recurrence (P = .047). The majority of recurrences (88%) were not salvageable. Progression‐free survival (PFS) and cause‐specific survival (CSS) for chemotherapy‐treated patients were more favorable than for those who did not receive chemotherapy (P = .013 and .081). Five‐year PFS and CSS rates were 81.5% and 87.6% in CT ± RT, 64.1% and 59.5% in RT alone, and 64.7% and 70.2% for OBS.

CONCLUSIONS:

Stage I UPSC patients have significant risk for extrapelvic recurrence and poor survival. Recurrence and survival outcomes are improved in well‐staged patients treated with platinum/taxane–based chemotherapy. This multi‐institutional study is the largest to support systemic therapy for early stage UPSC patients. Cancer 2009. © 2009 American Cancer Society.     

Survival outcomes with the use of surgery in limited‐stage small cell lung cancer

BACKGROUND:

Although chemotherapy and radiation therapy currently are recommended in limited‐stage small cell lung cancer (L‐SCLC), several small series have reported favorable survival outcomes in patients who underwent surgical resection. The authors of this report used a US population‐based database to determine survival outcomes of patients who underwent surgery.

METHODS:

The Surveillance, Epidemiology, and End Results (SEER) registry was used to identify patients who were diagnosed with L‐SCLC between 1988 and 2002 coded by SEER as localized disease (T1‐T2Nx‐N0) or regional disease (T3‐T4Nx‐N0). Kaplan‐Meier and Cox regression analyses were used to compare overall survival (OS) for all patients.

RESULTS:

In total, 14,179 patients were identified, including 863 patients who underwent surgical resection. Surgery was associated more commonly with T1/T2 disease (P < .001). Surgery was associated with improved survival for both localized disease and regional disease with improvements in median survival from 15 months to 42 months (P < .001) and from 12 months to 22 months (P < .001), respectively. Lobectomy was associated with the best outcome (P < .001). Patients with localized disease who underwent lobectomy with had a median survival of 65 months and a 5‐year OS rate of 52.6%; whereas patients who had regional disease had a median survival of 25 months and a 5‐year OS rate of 31.8%. On multivariate analysis, the benefit of surgery varied in a time‐dependant fashion. However, the benefit of lobectomy remained across all time intervals (P = .002).

CONCLUSIONS:

The use of surgery, and particularly lobectomy, in selected patients with L‐SCLC was associated with improved survival outcomes. Future prospective studies should consider the role of surgery as part of the multimodality management of this disease. Cancer 2010. © 2010 American Cancer Society.     

Recurrent esophageal carcinoma after esophagectomy with three-field lymph node dissection

To evaluate the effect of the extended lymphadenectomy for thoracic esophageal carcinoma, the pattern of recurrence in the 50 patients with pT3 tumors who underwent esophagectomy with cervical, mediastinal, and abdominal lymph node dissection (3-F) (group A) was compared with that of 100 patients at pT3 who underwent esophagectomy without upper mediastinal and cervical lymphadenectomy (2-F) (group B). The cumulative 5-year survival rate for 115 patients who underwent 3-F was 50.9%. Cumulative 5-year survival rates for patients in groups A and B were 36.8% and 22.0%, respectively. The survival curve for group A was significantly better than group B (P = 0.02332). Lymphatic recurrence was noted less frequently in group A (8/23) than in group B (31/49) (χ² = 5.1149), whereas the rate of hematogenous recurrence was similar. Extension of the field of lymph node dissection reduced the lymph node recurrence in patients with thoracic esophageal carcinoma, which may have positively affected patient survival. © 1996 Wiley-Liss, Inc.     

Smoking negatively impacts renal cell carcinoma overall and cancer-specific survival

BACKGROUND:

Tobacco use is a leading cause of premature death, yet few studies have investigated the effect of tobacco exposure on the outcome of patients with renal cell carcinoma (RCC). The authors of this report retrospectively studied the impact of smoking on clinicopathologic factors, survival outcomes, and p53 expression status in a large cohort of patients with RCC.

METHODS:

Eight hundred‐two patients (457 nonsmokers and 345 smokers) who had up to 232 months of follow‐up were compared for differences in their clinicopathologic features and survival outcomes. Immunohistochemical differences in p53 expression were correlated with smoking status.

RESULTS:

Smokers presented more commonly with pulmonary comorbidities (P < .0001) and cardiac comorbidities (P = .014) and with a worse performance status (P = .031) than nonsmokers. Smoking was associated significantly with tumor multifocality (P = .022), higher pathologic tumor classification (P = .037), an increased risk of bulky lymph node metastases (P = .031), and the presence of distant metastases (P < .0001), especially lung metastases (P < .0001). Both overall survival (OS) (62.37 months vs 43.64 months; P = .001) and cancer‐specific survival (CSS) (87.43 months vs 56.57 months; P = .005) were significantly worse in patients who smoked. The number of pack‐years was retained as an independent predictor of CSS and OS in patients with nonmetastatic disease. Mean expression levels of p53 were significantly higher in current smokers compared with former smokers and nonsmokers (P = .012).

CONCLUSIONS:

In patients with RCC, a history of smoking was associated with worse pathologic features and survival outcomes and with an increased risk of having mutated p53. Further investigation of the genetic and molecular mechanisms associated with decreased CSS in patients with RCC who have a history of smoking is indicated. Cancer 2012;. © 2011 American Cancer Society.     

Prediction of response to repeat utilization of anthracycline in recurrent breast cancer patients previously administered anthracycline-containing chemotherapeutic regimens as neoadjuvant or adjuvant chemotherapy

Summary Purpose: The aim of this study was to identify the predictors of the response to doxorubicin plus cyclophosphamide in patients with recurrent breast cancer (RBC) previously treated with anthracycline-containing regimens in a neoadjuvant or adjuvant setting. Method: Between December 1993 and October 2005, 664 patients had received combined doxorubicin plus cyclophosphamide chemotherapy (doxorubicin, 40 mg/m², iv on day 1; cyclophosphamide, 500 mg/m², iv on day 1, every 21 days) for RBC at our institution. In this study, we retrospectively analyzed the efficacy of doxorubicin plus cyclophosphamide in 99 of these 664 RBC patients who had also previously been administered an anthracycline-based chemotherapy in a neoadjuvant or adjuvant setting. Results: The median cumulative dose of the previously administered anthracycline was 156 mg/m². The median disease-free interval (DFI) and median anthracycline-free interval were 33.8 and 43.7 months, respectively. The overall response rate to doxorubicin plus cyclophosphamide therapy was 38.4% (95% CI; range, 28.8–48.0%). The median time to progression and overall survival were 6.2 and 17.5 months, respectively. The results of a multivariate logistic regression analysis revealed a significant association of the response to doxorubicin plus cyclophosphamide therapy with the DFI (P = 0.02); human epidermal receptor type 2 (HER2) status also tended to affect the response rate, however the association was not statistically significant (P = 0.06). Conclusion: DFI and HER2 status may be associated with the response to repeat utilization of anthracycline-containing regimens in RBC patients also treated previously with anthracycline-containing chemotherapeutic regimens in a neoadjuvant or adjuvant setting.     

Prognostic model to predict outcomes in nonsmall cell lung cancer patients treated with gefitinib as a salvage treatment

BACKGROUND:

A prognostic model based on clinical parameters for nonsmall cell lung cancer (NSCLC) patients treated with gefitinib (250 mg/day) as a salvage therapy was devised.

METHODS:

Clinical data regarding a total of 316 metastatic or recurrent NSCLC patients who were treated with gefitinib were analyzed.

RESULTS:

Poor prognostic factors for overall survival (OS) by multivariate analysis were an Eastern Cooperative Oncology Group (ECOG) performance status of 2 to 3 (hazards ratio [HR] of 2.07; 95% confidence interval [CI], 1.57‐2.73 [P < .001]), the presence of intra‐abdominal metastasis (HR of 1.76; 95% CI, 1.33‐2.34 [P < .001]), elevated serum alkaline phosphatase (HR of 1.50; 95% CI, 1.13‐2.00 [P = .005]), time interval from diagnosis to gefitinib therapy of ≤12 months (HR of 1.48; 95% CI, 1.12‐1.95 [P = .005]), low serum albumin (HR of 1.45; 95% CI, 1.09‐1.92 [P = .009]), progression‐free interval for previous chemotherapy of ≤12 weeks (HR of 1.40; 95% CI, 1.0‐1.84 [P = .015]), white blood cell >10,000/μL (HR of 1.38; 95% CI, 1.02‐1.85 [P = .032]), and ever‐smoker (HR of 1.33; 95% CI, 1.02‐1.75 [P = .033]). Of the 272 patients applicable to this prognostic model, 41 patients (15%) were categorized as a good prognosis group (0‐1 risk factors), 100 patients (37%) as an intermediate prognosis group (2‐3 risk factors), 81 patients (30%) as a poor prognosis group (4‐5 risk factors), and 50 patients (16%) as a very poor prognosis group (≥6 risk factors). The median OS from the time of gefitinib treatment for the good, intermediate, poor, and very poor prognosis groups were 18.0 months, 11.2 months, 4.0 months, and 1.3 months, respectively (P < .001).

CONCLUSIONS:

This prognostic model based on easily available clinical variables would be useful to identify patients who might derive more benefit from gefitinib treatment and to make decisions in clinical practice. Cancer 2009. © 2009 American Cancer Society.