Comprehensive treatment of malignant mesothelioma patients after the failure of systemic chemotherapy

Malignant mesothelioma (MM) is an aggressive neoplasm usually arising from the mesothelial surfaces of the pleural or peritoneal cavity. Currently, no standard therapy is available. The most commonly used therapy is cytoreductive surgery combined with systematic chemotherapy, but the median overall survival (OS) is less than 12 months; moreover, treatments are lacking for patients in whom chemotherapy has failed and/or who cannot withstand surgery. We investigated multiple minimally invasive therapies (cryosurgery, photodynamic therapy and intracavity chemotherapy) for the treatment of MM patients in whom systemic chemotherapy had failed. Twenty-seven patients were divided into comprehensive (combination of the three therapies) and palliative (intracavity chemotherapy only) treatment groups. The OS of patients who received comprehensive treatment was significantly longer than that of those who received palliative treatment (median OS: 64 vs. 9 months, P < 0.001). This interesting result was not associated with treatment timing, but was closely associated with repeated treatments.     

Percutaneous cryoablation for stage IV lung cancer: A retrospective analysis

The aim of this study was to investigate the therapeutic effect of cryoablation treatment and palliative treatment in stage IV lung cancer. Fifty-four patients were enrolled into the study. Thirty-one patients received cryoablation treatment (including intra- and extrapulmonary tumors), and 23 patients had palliative treatment (no cryoablation). Both the safety of the procedure and overall survival (OS) for stage IV lung cancer were assessed during a 6.5 year follow-up period. The OS of patients in both groups and the effects of treatment timing and frequency were compared. The OS in the cryoablation group was significantly longer than in the palliative group (median OS: 14 months vs. 7 months, P = 0.0009). The OS of those who received delayed cryoablation treatment was longer than that observed for those who received timely treatment (median OS: 18.5 months vs. 10 months, P = 0.0485), but this was not observed in those who received palliative treatment (median OS: 7 months vs. 7.5 months, P = 0.9814). Multiple treatments played an important role in improving the OS of patients who received cryoablation treatment (median OS: 18 months vs. 14 months, P = 0.0376). There was a significant difference between cryoablation and palliative treatment, in terms of OS. In addition, multiple cryoablation treatments may have an advantage over single treatments.     

Therapeutic outcomes of combining cryotherapy,chemotherapy and DC-CIK immunotherapy in the treatment of metastatic non-small cell lung cancer

Currently there are no effective therapies for the treatment of metastatic non-small cell lung cancer (NSCLC). Here, we conducted a retrospective study of 161 patients to evaluate the therapeutic effects of combining cryosurgery, chemotherapy and dendritic cell-activated cytokine-induced killer cells (DC-CIK) immunotherapy. The overall survival (OS) after diagnosis of metastatic NSCLC to patient death was assessed during a 5-years follow-up period. OS of patients who received comprehensive cryotherapy was (median OS, 20 months; n = 86) significantly longer than that of patients who did not received cryotherapy (median OS, 10 months; n = 75; P < 0.0001). Five treatment combinations were selected: chemotherapy (n = 44); chemo-immunotherapy (n = 31); cryo-chemotherapy (n = 32); cryo-immunotherapy (n = 21); and cryo-chemo-immunotherapy (n = 33). A combination of cryotherapy with either chemotherapy or immunotherapy lead to significantly longer OS (18 months and 17 months, respectively) compared to chemotherapy and chemo-immunotherapy (8.5 months and 12 months, respectively; P < 0.001); however, the median OS of patients who underwent cryo-chemo-immunotherapy was significantly longer (27 months) compared to the other treatment programs (P < 0.001). In conclusion, a combination of cryotherapy, chemotherapy and DC-CIK immunotherapy proved the best treatment option for metastatic NSCLC in this group of patients.     

Percutaneous comprehensive cryoablation for metastatic esophageal cancer after failure of radical surgery

Esophageal cancer is common in China. There is a lack of treatment strategies for metastatic esophageal cancer (MEC) after radical surgery on the primary tumor. Cryoablation is an attractive option because tumor necrosis can be safely induced in a minimally invasive manner. This study assessed its therapeutic effect in MEC after failure of radical surgery. One hundred and forty patients met the inclusion criteria from May, 2003 to March, 2011. Comprehensive cryotherapy of multiple metastases was performed on 105 patients; 35 received chemotherapy. No severe complications occurred during or after cryoablation. Overall survival (OS) was assessed according to therapeutic protocol, pathologic type, treatment timing and number of procedures. The OS of patients who received comprehensive cryoablation (44 ± 20 months) was significantly longer than that of those who underwent chemotherapy (23 ± 24 months; P = 0.0006). In the cryotherapy group, the OS for squamous cell carcinoma (45 ± 19 months) was longer than that for adenocarcinoma (33 ± 18 months; P = 0.0435); the OS for timely cryoablation (46 ± 19 months) was longer than that for delayed cryoablation (33 ± 20 months; P = 0.0193); the OS for multiple cryoablation (50 ± 17 months) was longer than that for single cryoablation (37 ± 20 months; P = 0.0172); and the OS for cryo-immunotherapy (56 ± 17 months) was longer than that for cryoablation alone (39 ± 19 months; P = 0.0011). Thus, comprehensive cryotherapy may have advantages over chemotherapy in the treatment of MEC and, in patients with squamous cell carcinoma, supplementary immunotherapy and timely and multiple cryoablation may be associated with a better prognosis.     

Cryotherapy protocols for metastatic breast cancer after failure of radical surgery

To retrospectively assess the effect of cryotherapy in patients with metastatic breast cancer (MBC) but without local recurrence after resection of the primary lesion, we divided 120 MBC patients into cryotherapy (91 patients) and chemotherapy (29 patients) groups. In the cryotherapy group, 37 patients with tumor recurrence received multiple cryoablations, while 54 patients received only a single cryoablation. Moreover, 62 cryotherapy-group patients underwent cryoablation immediately after the detection of metastases (timely cryotherapy); 35 patients received simultaneous immunotherapy (cryo-immunotherapy), and 29 patients underwent cryoablation in our hospital 3 months after receiving chemotherapy in other centers (chemo-cryotherapy and delayed cryotherapy). Overall survival (OS) after the diagnosis of MBC was assessed after a 10-year follow-up. The median OS was higher in the cryotherapy group (55 months) than in the chemotherapy group (27 months; P < 0.0001). In the cryotherapy group, longer median OS was associated with multiple (76 months) rather than single cryoablations (48 months; P = 0.0005) and with timely (67 months) rather than delayed cryoablation (48 months; P = 0.0012). The median OS was higher after cryo-immunotherapy (83 months) than after chemo-cryotherapy (48 months) or cryotherapy alone (43 months; P < 0.0001 for both). In conclusion, timely and multiple cryoablations, especially when combined with immunotherapy, offer significant advantages over chemotherapy in extending the OS of MBC patients.     

Adjuvant Therapy for Thymic Carcinoma – A Decade of Experience in a Taiwan National Teaching Hospital

Background

Thymic carcinomas are rare tumors for which surgical resection is the first treatment of choice. The role of adjuvant treatment after surgery is unknown because of limited available data. The present study evaluated the efficacy of post-surgery adjuvant chemotherapy or radiotherapy in patients with thymic carcinoma.

Methods

To evaluate the role of adjuvant therapy in patients with thymic carcinoma, we retrospectively reviewed the records of patients with thymic carcinoma who were diagnosed and treated between 2004 and 2014.

Results

Among 78 patients with thymic carcinoma, 30 patients received surgical resection. Progression-free survival (PFS) and overall survival (OS) were significantly longer among these patients than among patients who received other treatments (PFS: 88.4 months vs 9.1 months, p<0.001; OS: 134.9 months vs 60.9 months; p = 0.003). Patients with stage III thymic carcinoma who received surgery had a longer OS than patients who did not receive surgery (70.1 months vs 23.9 months; p = 0.017, n = 11). Among 47 patients with stage IV carcinoma, 12 patients who received an extended thymothymectomy had a longer PFS than 35 patients who did not receive surgery (18.9 months vs 8.7 months; p = 0.029). Among 30 patients (with stage I- IV carcinoma) who received primary lesion surgery, 19 patients received an R0 resection and 9 patients of the 19 patients received adjuvant radiotherapy. These patients had longer PFS (50.3 months) than 2 patients who received adjuvant chemotherapy (5.9 months) or 4 patients who received concurrent chemoradiotherapy (7.5 months) after surgery (p = 0.003).

Conclusions

Surgical resection should be considered for patients with thymic carcinoma, even for patients with locally advanced or stage IV carcinoma. Adjuvant radiotherapy resulted in a better PFS after R0 resection.     

Survival and prognostic factors for patients with melanoma brain metastases in the era of modern systemic therapy

Historically, the prognosis of patients with melanoma brain metastases is poor, with median overall survival (OS) of 4‐6 months. Little is known of OS in the era of modern systemic therapies and local therapy with stereotactic radiosurgery (SRS) or surgery. Patients diagnosed with melanoma brain metastases at Melanoma Institute Australia from January 2011 to December 2014 were included. OS and prognostic factors were analysed using Cox regression and Kaplan‐Meier survival analyses.355 patients were included. The median OS was 7.1 months (95% confidence interval [CI] 6.0‐8.1). Median OS differed by treatment modality: systemic therapy and SRS and/or surgery 14.9 months (95% CI 10.7‐19.0), SRS and/or surgery with or without whole brain radiotherapy (WBRT) 6.4 months (95% CI 5.4‐7.5), systemic therapy 5.4 months (95% CI 3.1‐7.7), systemic therapy and WBRT 5.2 months (95% CI 4.1‐6.4), WBRT 4.4 months (95% CI 2.4‐6.3), and best supportive care 1.8 months (95% CI 1.2‐2.3). OS for patients with melanoma brain metastases appears improved in the modern era, particularly for patients who are candidates for systemic therapy with SRS and/or surgery.     

Radioembolisation des tumeurs hépatiques par microsphères marquées à l’yttrium-90

This study is a retrospective analysis of 64 patients with a primary or secondary liver malignancy, referred for yttrium-90 radioembolisation between December 2006 and September 2010. Among these 64 patients, 54 received a total number of 69 injections (one to three treatments per patient). The mean activity injected per treatment was 3.1 ± 1.6 GBq. The liver targeted dose was 123.1 ± 39 Gy. Pulmonary shunt, detected in 55% of treatments, was 5.7% ± 7.4. The pulmonary dose was 4.7 ± 7.1 Gy. Overall, response rate per patient, evaluated at 3 months by EASL or modified RECIST criteria, was 72.9%, 70% for hepatocellular carcinoma. The complication rate was relatively low (17%) with only two serious events. ⁹⁰Y-microspheres radioembolisation of liver malignancies is an effective and well-tolerated therapy. Until now often used as a salvage therapy, the recent and ongoing studies should better define its place in the therapeutic strategy (adjuvant, neoadjuvant, first line) and possible association with chemotherapy and targeted therapies.     

Real-world effectiveness and safety of multiple myeloma treatments based on thalidomide and bortezomib: A retrospective cohort study from 2009 to 2020 in a Brazilian metropolis

BackgroundMultiple myeloma (MM) is an incurable cancer of plasma cells; the survival of which has improved over the years with the emergence of new treatments. In Brazil, the availability of treatment-regimens is different from developed countries. Real-world evidence with Brazilian patients is lacking.ObjectivesOur aim was to evaluate the effectiveness and the safety of MM treatments in a Brazilian metropolis.MethodsThis was a retrospective cohort study with MM patients, beginning MM treatment from 2009 to 2020 (i.e., before bortezomib became available in public health services). Patients’ medical records were revised to obtain clinical variables. The primary outcomes were Overall Survival (OS) and Progression Free Survival (PFS, measured as time to next treatment), and the secondary outcomes were Adverse Events (AE). Kaplan-Meier curves were obtained and the Cox proportional hazards model was performed for univariate and multivariate analyses. The incidence of AE was estimated and the chi-squared test was performed to evaluate the association between AE and MM regimens.ResultsIn total, 278 patients participated in the study with median age of 64 years; 50.4 % were females, 55.8 % attended a private clinic, 34.9 % received autologous stem cell transplantation (ASCT) and 32.4 % were on polypharmacy. Most patients from public services used thalidomide-based regimens (40.3 %) and at private clinics used bortezomib-based regimens (38.1 %) as first-line treatment. Patients had a median OS of 99 months. Patients had median PFS of 28 months in first-line treatment, which was significantly different for age (p = 0.0055), polypharmacy (p = 0.0094) and ASCT (p < 0.0001). PFS was independently associated to polypharmacy and ASCT. The incidence of peripheral neuropathy (39.6 %) was high. In contrast, the incidence of severe AE was low. We found significant difference between first-line T + B-based regimens and leukopenia (p = 0.012).ConclusionOur study showed that patients on polypharmacy and who did not receive ASCT had worse PFS. Similar to other Latin countries, most patients used thalidomide- and bortezomib-based regimens as first-line treatments having similar OS and PFS. Treatments were considered relatively safe, especially regarding serious AE.     

ERCC1 expression as a prognostic and predictive factor in patients with non-small cell lung cancer: a meta-analysis

It is hypothesized that high expression of the excision repair cross-complementation group 1 (ERCC1) gene might be a positive prognostic factor, but predict decreased sensitivity to platinum-based chemotherapy. Results from the published data are inconsistent. To derive a more precise estimation of the relationship between ERCC1 and the prognosis and predictive response to chemotherapy of non-small cell lung cancer (NSCLC), a meta-analysis was performed. An electronic search of the PubMed and Embase database was performed. Hazard ratio (HR) for overall survival (OS) was pooled in early stage patients received surgery alone to analyze the prognosis of ERCC1 on NSCLC. HRs for OS in patients received surgery plus adjuvant chemotherapy and in patients received palliative chemotherapy and relative risk (RR) for overall response to chemotherapy were aggregated to analyze the prediction of ERCC1 on NSCLC. The pooled HR indicated that high ERCC1 levels were associated with longer survival in early stage patients received surgery alone (HR, 0.69; 95% confidence interval (CI), 0.58–0.83; P = 0.000). There was no difference in survival between high and low ERCC1 levels in patients received surgery plus adjuvant chemotherapy (HR, 1.41; 95% CI, 0.93–2.12; P = 0.106). However, high ERCC1 levels were associated with shorter survival and lower response to chemotherapy in advanced NSCLC patients received palliative chemotherapy (HR, 1.75; 95% CI, 1.39–2.22; P = 0.000; RR, 0.77; 95% CI, 0.64–0.93; P = 0.007; respectively). The meta-analysis indicated that high ERCC1 expression might be a favourable prognostic and a drug resistance predictive factor for NSCLC.     

Transarterial chemoembolisation (TACE) using irinotecan-loaded beads for the treatment of unresectable metastases to the liver in patients with colorectal cancer: an interim report

Background

Following failure of standard systemic chemotherapy, the role of hepatic transarterial therapy for colorectal hepatic metastasis continues to evolve as the experience with this technique matures. The aim of this study to gain a better understanding of the value of drug eluting bead therapy when administered to patients with unresectable colorectal hepatic metastasis.

Methods

This was an open-label, multi-center, single arm study, of unresectable colorectal hepatic metastasis patients who had failed standard therapy from 10/2006-10/2008. Patients received repeat embolizations with Irinotecan loaded beads(max 100 mg per embolization) per treating physician's discretion.

Results

Fifty-five patients underwent 99 treatments using Irinotecan drug eluting beads. The median number of total treatments per patient was 2(range of 1-5). Median length of hospital stay was 23 hours(range 23 hours - 10 days). There were 30(30%) sessions associated with adverse reactions during or after the treatment. The median disease free and overall survival from the time of first treatment was 247 days and 343 days. Six patients(10%) were downstaged from their original disease status. Of these, four were treated with surgery and two with RFA. Neither number of liver lesions, size of liver lesions or extent of liver replacement(<= 25% vs >25%) were predictors of overall survival. Only the presence of extrahepatic disease(p = 0,001), extent of prior chemotherapy (failed 1^st and 2^nd line vs > 2 line failure)(p = 0,007) were predictors of overall survival in multivariate analysis.

Conclusion

Chemoembolization using Irinotecan loaded beads was safe and effective in the treatment of patients as demonstrated by a minimal complication rate and acceptable tumor response.     

Effects of locoregional radiotherapy in de novo metastatic nasopharyngeal carcinoma: A real-world study

BackgroundTo evaluate the value of locoregional radiotherapy (LRRT) in de novo metastatic nasopharyngeal carcinoma (dmNPC) and identify predictive factors for additional LRRT after palliative chemotherapy (PCT).MethodsOverall survival (OS) was the primary endpoint. Patients who underwent PCT and LRRT were categorized as the PCT+LRRT group; patients who only received palliative chemotherapy were categorized as the PCT group. Oligometastatic diseases (OMD) was defined as ≤5 metastatic lesions and ≤2 metastatic organs.ResultsA total of 168 patients were included for this study. The median OS of patients in the PCT+LRRT group was significantly higher than those in the PCT group (57 months vs. 22 months, P<0.001). Multivariate analyses (MVA) showed that LRRT (HR=0.533, 95% CI: 0.319–0.889, P = 0.016) and OMD (HR=0.548, 95% CI: 0.331–0.907, P = 0.019) were independent prognostic factors for dmNPC. Furthermore, Kaplan–Meier analyses showed that the 3-year OS of patients who received LRRT was significantly better than those who did not receive LRRT in the OMD subgroup (66.3% vs. 25.2%, P<0.001). While, the 3-year OS of patients who received LRRT and without LRRT was no different in the polymetastatic disease (PMD) subgroup (38.9% vs.11.5%, P = 0.115). MVA showed that LRRT was a favorable prognosticator in the OMD subgroup (HR=0.308, 95% CI: 0.159–0.598; P<0.001), and not a favorable prognosticator in the PMD subgroup (HR=0.510, 95% CI: 0.256–1.014, P = 0.055).ConclusionsLRRT has the potential to prolong OS in NPC patients with de novo OMD. These results suggest that OMD is a potential indicator for filtering beneficiaries from LRRT.     

The Role of Non-Curative Surgery in Incurable,Asymptomatic Advanced Gastric Cancer

Background

Although general agreement exists on palliative surgery with intent of symptom palliation in advanced gastric cancer (AGC), the role of non-curative surgery for incurable, asymptomatic AGC is hotly debated. We aim to clarify the role of non-curative surgery in patients with incurable, asymptomatic AGC under the first-line chemotherapy.

Methods

A total of 737 patients with incurable, asymptomatic advanced gastric adenocarcinoma between January 2008 and May 2012 at the Sun Yat-sen University Cancer Center were retrospectively analyzed, comprising 414 patients with non-curative surgery plus first-line chemotherapy, and 323 patients with first-line chemotherapy only. The clinicopathologic data, survival, and prognosis were evaluated, with propensity score adjustment for selection bias.

Results

The median overall survival (OS) outcomes significantly favored non-curative surgery group over first-line chemotherapy only group in entire population (28.00 versus 10.37 months, P = 0.000), stage 4 patients (23.87 versus 10.37 months, P = 0.000), young patients (28.70 versus 10.37 months, P = 0.000) and elderly patients (23.07 versus 10.27 months, P = 0.031). The median OS advantages of non-curative surgery over first-line chemotherapy only were also maintained when the analyses were restricted to single organ metastasis (P = 0.001), distant lymph node metastasis (P = 0.002), peritoneal metastasis (P = 0.000), and multi-organ metastasis (P = 0.010). Significant OS advantages of non-curative surgery over chemotherapy only were confirmed solid by multivariate analyses before and after adjustment on propensity score (P = 0.000). Small subsets of patients with surgery of single metastatic lesion after previous curative gastrectomy, and with surgery of both primary and single metastatic sites showed sound median OS.

Conclusions

There is a role for non-curative surgery plus first-line chemotherapy for incurable, asymptomatic AGC, in terms of survival. Randomized controlled trials are warranted to fill a gap in knowledge about the value of metastectomy and patient selection strategies.     

The impact of local control timing in Ewing sarcoma

AimTo assess the impact of delay in local control on survival outcomes of Ewing sarcoma (ES) patients.BackgroundThe cornerstone of therapy of localized ES includes chemotherapy and local control with surgery or radiotherapy. We sought to assess the impact of delay (>15 weeks) in timing of local control on survival outcomes of ES patients.MethodsData of consecutive patients with primary non-metastatic ES of the extremities, treated at a single institution were collected. The impact of delay of timing for local control, demographics, and disease characteristics on overall survival (OS) was analyzed.ResultsA total of 43 patients with ES of the extremity were included. All patients received neoadjuvant chemotherapy. Local control was by surgery in 36 patients and definitive radiation in 7. A total of 16 patients had delay in local control. At a median follow of up of 48 months, patients with delay in local control had significantly inferior OS compared to those with optimal local control timing (5-year OS 56% vs. 80%, respectively, p = 0.044). Other factors that predicted inferior OS included definitive radiation as opposed to definitive surgery (5-year OS 25% vs. 79%, respectively, p = 0.041) and tumor necrosis <90% as opposed to ≥90% (5-year OS 55% vs. 90%, respectively, p = 0.01).ConclusionDelay in definitive therapy, local control with radiation as opposed to surgery and poor post-chemotherapy tumor necrosis predict inferior OS in ES. Adopting strategies to minimize delay in local control could improve survival outcomes.     

Advanced prostate cancer: an update

A number of therapeutic options are available or on the horizon for patients for whom initial treatment of localized prostate cancer has failed. Currently under study are time of therapy, maximum androgen blockade, and palliative and adjunctive therapies.     

Combined therapy of percutaneous cryoablation and traditional Chinese medicine can be a promising strategy for elderly or advanced lung cancer patients based on a retrospective clinical study

Presently, elderly and advanced lung cancer patients have very limited treatment options. With no promising therapy, treatment of these patients is challenging. We have reviewed 119 primary lung cancer patients who received a combined percutaneous cryoablation and traditional Chinese medicine therapy (Cryo-TCM therapy) between 2005 and 2013. Out of 119 patients, 84.1% patients were elderly or advanced lung cancer when receiving cryoablation. Overall Survival time from the time of Diagnosis (DOS) and Cryoablation (COS) was 19 and 10 months respectively, which were longer than data previously published. Patients who accepted only Cryo-TCM therapy got similar DOS as those who were treated with Cryo-TCM and other classic anticancer therapies. Thus, Cryo-TCM therapy can prolong the survival time and can be used as the main therapy for the elderly or advanced lung cancer patients in China both in quality of life and cost effectiveness.     

Simultaneous Integrated Boost Radiotherapy in Unresectable Stage IV (M0) Head and Neck Squamous Cell Cancer Patients: Daily Clinical Practice

AimTo evaluate clinical outcome in locally-advanced stage IV (M0) head and neck cancer patients treated using intensity-modulated radiotherapy (IMRT) with simultaneous integrated boost (SIB) in daily clinical practice.BackgroundDespite SIB-IMRT has been reported as a feasible and effective advanced head and neck cancer treatment, there are few data about its concurrent use with systemic therapies.Material and MethodsWe reviewed 41 staged IV (M0) head and neck cancer patients treated in two radiotherapy units in the city of Messina (Italy) during the last six years, using intensity modulated techniques-SIB. 22/41 patients had concomitant chemotherapy or cetuximab. Acute and late toxicities, objective response (OR) rate, local control (LC) and overall survival (OS) have been evaluated.Results37/41 patients received the planned doses of radiotherapy, 2 patients died during the therapy. The major acute regional toxicities were skin reaction and mucositis. A case of mandibular osteoradionecrosis was recorded. At completion of treatment, OR was evaluated in 38 patients: 32/38 patients (84.2%) had complete (55.3%) and partial (28.9%) response. The 1- and 5-year LC rates were 73.4% and 69.73%, respectively. The 1-, 3-, and 5-year OS rates were 85.93%, 51.49% and 44.14%, respectively. No statistically significant differences in outcomes have been observed in patients treated with radiotherapy alone vs. irradiation concomitant to chemo/biotherapy. The median OS was 45 months.ConclusionSIB-IMRT is safeand can be used with concomitant chemotherapy/biotherapy in real-life daily clinical practice. SIB-IMRT alone is a valid alternative in patients unfit for systemic therapies.     

Treatment and outcome of patients with metastatic NSCLC: a retrospective institution analysis of 493 patients

Background

Most patients with metastatic non-small cell lung cancer (NSCLC) will face treatment with systemic therapy. Current clinical studies are demonstrating improvements in chemotherapy and overall survival. However, it remains unclear whether these results are translated into clinical practice.

Methods

We reviewed all stage IV NSCLC patients without second malignancies that were diagnosed from 2004 to 2006 at our institution. 493 consecutive patients were included into this retrospective analysis and were followed-up until end of 2011.

Results

352 patients (71.4%) received systemic therapy for up to 7 lines. For most patients, adjustments of dosages or applications had to be made at some point of the treatment, but the total applied dose remained generally close to the intended dose. The best disease control (BDC) rate decreased with increasing therapy lines from 59.7% to about 35%. Patients with palliative local therapy but no systemic treatment demonstrated inferior survival (median 2.9 versus 8.7 months, p < 0.001). The median interval between last treatment and death was 50 days and 15 days for chemotherapy and anti-EGFR therapy, respectively. BDC to the previous therapy lines was predictive for improved BDC to third- but not second-line therapy. Performing multivariate analysis, BDC to previous therapy, never-/ former-smoking status, and age > 70 years were associated with improved survival performing third-line therapy.

Conclusions

Stage IV NSCLC patients may receive substantial systemic therapy resulting in response and median survival rates that are comparable to data from clinical studies. However, preselection factors are increasingly important to improve therapy outcome and life quality.     

Optimal Duration of Fluorouracil-Based Adjuvant Chemotherapy for Patients with Resectable Gastric Cancer

Background

Although several clinical trials have suggested that postoperative adjuvant chemotherapy can improve survival of patients with gastric cancer, the optimal treatment duration has not been studied. This retrospective analysis evaluated the outcomes of patients with gastric cancer treated with six cycles of fluorouracil-based treatment compared with a cohort treated with four or eight cycles.

Methods

We retrospectively identified 237 patients with stage IB–IIIC gastric cancer who received four, six, or eight cycles of fluorouracil-based adjuvant chemotherapy administered every 3 weeks after radical gastrectomy. The endpoint was overall survival (OS). Factors associated with prognosis were also analyzed.

Results

The estimated 3-year OS rates for the four-, six-, and eight-cycle cohorts were 54.4%, 76.1%, and 68.9%, respectively; and the estimated 5-year OS rates were 41.2%, 74.0%, and 65.8%, respectively. Patients who received six cycles were more likely to have a better OS than those who received four cycles (P = 0.002). Eight cycles failed to show an additional survival benefit (P = 0.454). In the multivariate analysis, the number of chemotherapy cycles was associated with OS independent of clinical covariates (P<0.05). Subgroup analysis suggested that among patients in all age groups examined, male patients, and subgroups of fluorouracil plus oxaliplatin combined chemotherapy, stage III, poor differentiation, and gastrectomy with D2 lymphadenectomy, six cycles of adjuvant chemotherapy were associated with a statistically significant benefit of OS compared with four cycles (P<0.05).

Conclusions

Six cycles of adjuvant chemotherapy might lead to a favorable outcome for patients with gastric cancer, and two further cycles could not provide an additional clinical benefit.     

Methylation status of IGFBP-3 as a useful clinical tool for deciding on a concomitant radiotherapy

The methylation status of the IGFBP-3 gene is strongly associated with cisplatin sensitivity in patients with non-small cell lung cancer (NSCLC). In this study, we found in vitro evidence that linked the presence of an unmethylated promoter with poor response to radiation. Our data also indicate that radiation might sensitize chemotherapy-resistant cells by reactivating IGFBP-3-expression through promoter demethylation, inactivating the PI3K/AKT pathway. We also explored the IGFBP-3 methylation effect on overall survival (OS) in a population of 40 NSCLC patients who received adjuvant therapy after R0 surgery. Our results indicate that patients harboring an unmethylated promoter could benefit more from a chemotherapy schedule alone than from a multimodality therapy involving radiotherapy and platinum-based treatments, increasing their OS by 2.5 y (p = .03). Our findings discard this epi-marker as a prognostic factor in a patient population without adjuvant therapy, indicating that radiotherapy does not improve survival for patients harboring an unmethylated IGFBP-3 promoter.