Prognostic implication of pulmonary function at the beginning of postoperative radiotherapy in non-small cell lung cancer

PurposeThe purpose of this study was to investigate the prognostic effect of pulmonary function at the beginning of postoperative radiotherapy (PORT) in non-small cell lung cancer (NSCLC).Materials and methodsFrom January 2002 to December 2012, 115 patients with NSCLC who underwent PORT and took the forced expiratory volume in 1 second (FEV1) at the beginning of PORT were analysed. PORT began within 4–6 weeks following surgery, and the 3-dimensional conformal technique was used with conventional fractionation. The high and low FEV1 groups were divided by the median absolute value of FEV1 at the beginning of PORT, and we compared the clinical factors and survival between two groups.ResultsThe median absolute value of FEV1 at the beginning of PORT was 1.68 L (range, 0.83–3.89), and patients were divided into low and high FEV1 groups (<1.68 L versus ⩾1.68 L). Patients in the low FEV1 group showed a lower preoperative FEV1 (mean, 1.94 L versus 2.73 L, p < 0.001) and received more pneumonectomy (36.8% versus 8.6%, p < 0.001) compared to the high FEV1 group. The overall median follow-up time was 31 months (range, 3–110), and 5-year locoregional recurrence-free survival (LRRFS), distant metastasis-free survival (DMFS) and overall survival (OS) were 52.4%, 48.9%, and 45.9%, respectively. Five-year OS of the low FEV1 group was significantly lower than that of the high FEV1 group (35.4% versus 56.9%, p = 0.002), and no significant differences were found in LRRFS and DMFS. In a multivariate analysis, the difference of OS between the low and high FEV1 groups remained significant (Hazard Ratio = 2.04, CI, 1.18–3.55, p = 0.011).ConclusionsThe FEV1 at the beginning of PORT was an independent significant prognostic factor in patients with NSCLC who received PORT. Considering this analysis was limited to only patients receiving PORT, further studies are warranted to compare the survival effect of postoperative pulmonary function between groups with/without PORT.     

Radiothérapie stéréotaxique (RTST) pulmonaire des tumeurs de moins de 3 cm (stade I) et 5 cm (stade II) non opérées : 10 ans d’expérience de l’Institut du Cancer de Montpellier (ICM)

PurposeSearch for predictive factors on survival and local control for less than 3 centimeters (cm) (stage I) and 5 cm (stage II) inoperable lung tumors treated by Stereotactic Body Radiation Therapy (SBRT) in a retrospective monocentric study from Montpellier Cancer Institute (ICM)Patients and methodEvery patients treated at ICM for a stage I or II inoperable lung tumors from 2009 to 2019 were analyzed.ResultsOne hundred and seventy nine lesions were treated in 176 patients, with a major part (82,7%) in operated due to chronic obstructive pulmonary disease. Median overall survival for all patients was 71,7 months with a 35 months follow-up and the 2 years loco-regional free survival was 94,0 months. Better associated outcomes were stage I (median overall survival 71,7 versus 29,0 months P = 0,004 ; HR = 2,37 P = 0,005), BED ≥ 150 Gy (median time-to-progression not reached versus 76,7 months P = 0,025), small size of Planning Target Volume (PTV) (HR = 0,42 P = 0,032 when PTV < 15,6 cc). 7,3% of all patients developed radiation pneumonitis.ConclusionSBRT is associated with an excellent overall survival and a high rate of local control for less than 3 cm (stage I) and 5 cm (stage II) lung tumors but a low rate of toxicities. For these patients with many comorbidities, BED over 150 Gy seems to be associated with a better loco-regional free survival, while cause of death is often other than lung cancer.     

Comorbidity,age, and mortality among adults treated intensively for acute myeloid leukemia (AML)

IntroductionOur goal was to characterize comorbidities among adults receiving intensive therapy for AML, and investigate their association with outcomes.MethodsWe retrospectively analyzed 277 consecutive patients with newly diagnosed AML treated intensively at the Comprehensive Cancer Center of Wake Forest University from 2002 to 2009. Pretreatment comorbidities were identified by ICD-9 codes and chart review. Comorbidity burden (modified Charlson Comorbidity Index [CCI]) and specific conditions were analyzed individually. Outcomes were overall survival (OS), remission, and 30-day mortality. Covariates included age, gender, cytogenetic characteristics, hemoglobin, white cell count, lactate dehydrogenase, body mass index, and insurance type. Cox proportional hazards models were used to evaluate OS; logistic regression was used for remission and 30-day mortality.ResultsIn this series, 144 patients were ≥ 60 years old (median age 70 years, median survival 8.7 months) and 133 were < 60 years (median age 47 years, median survival 23.1 months). Older patients had a higher comorbidity burden (CCI ≥ 1 58% versus 26%, P < 0.001). Prevalent comorbid conditions differed by age (diabetes 19.2% versus 7.5%; cardiovascular disease 12.5% versus 4.5%, for older versus younger patients, respectively). The CCI was not independently associated with OS or 30-day mortality in either age group. Among older patients, diabetes was associated with higher 30-day mortality (33.3% vs. 12.0% in diabetic vs. non-diabetic patients, p = 0.006). Controlling for age, cytogenetic characteristics and other comorbidities, the presence of diabetes increased the odds of 30-day mortality by 4.9 (CI 1.6–15.2) times.DiscussionDiabetes is adversely associated with 30-day survival in older AML patients receiving intensive therapy.     

Lung stereotactic radiation therapy: Intercomparison of irradiation devices in terms of outcome and predictive factors

PurposeTo compare three different radiotherapy devices able to perform pulmonary stereotactic radiotherapy: CyberKnife® (CK), Helical Tomotherapy® (HT), and volumetric modulated arc therapy (VMAT). This study aims to define the patients’ outcome in terms of SBRT efficacy and toxicities depending of the device choice.Materials and methodsWe retrospectively analyzed the clinical, radiological, and dosimetric data of patients treated with lung SBRT between 2016 and 2020 at Lausanne University Hospital, using the Chi² test for proportions, the t-test for means comparisons, the Kaplan-Meier method for survival, and the Log-rank test and Cox-regression for intergroups comparisons.ResultsWe identified 111 patients treated by either CK (59.9%), VMAT (38.0%), or HT (2.1%). Compared to other techniques, CK treated comparable gross tumor volume (GTV; 2.1 vs. 1.4 cm³, P = 0.84) with smaller planning treatment volume (PTV; 12.3 vs. 21.9 cm³, P = 0.013) and lower V5 (13.5 vs. 19.9 cm³, P = 0.002). Local control rates at 2 years were not different whatever the irradiation device, respectively of 96.2% (range, 90.8–100) and 98.1% (range, 94.4–100), P = 0.68. Toxicity incidence significantly increased with V5 value > 17.2% (56.0 vs. 77.4%, P = 0.021).ConclusionCompared to other SBRT techniques, CK treatments permitted to treat comparable GTV with reduced PTV and V5. Toxicity incidence was less frequent when reducing the V5. CK is particularly attractive in case of multiple courses of lung SBRT or lung reirradiation.     

Could conventionally fractionated radiation therapy coupled with stereotactic body radiation therapy improve local control in bone oligometastases?

PurposeTo describe clinical outcomes of stereotactic body radiation therapy (SBRT) applied alone or as a boost after a conventionally fractionated radiation therapy (CFRT) for the treatment of bone oligometastases.Material and MethodsThis retrospective cohort study included patients treated with SBRT from January 2007 to December 2015 in the Institut de cancérologie de Lorraine in France. The inclusion criteria involved adults treated with SBRT for one to three bone metastases from a histological proven solid tumor and a primary tumor treated, an Eastern Cooperative Oncology Group (ECOG) score inferior or equal to 2. Local control (LC), overall survival (OS), progression free survival (PFS), bone progression incidence (BPI), skeletal related events free survival (SRE-FS), toxicity and pain response were evaluated.ResultsForty-six patients and 52 bone metastases were treated. Twenty-three metastases (44.2%) received SBRT alone mainly for non-spine metastases and 29 (55.8%) a combination of CFRT and SBRT mainly for spine metastases. The median follow-up time was 22 months (range: 4–89 months). Five local failures (9.6%) were observed and the cumulative incidences of local recurrence at 1 and 2 years respectively were 4.4% and 8% with a median time of local recurrence of 17 months (range: 4–36 months). The one- and two-years OS were 90.8% and 87.4%. Visceral metastasis (HR: 3.40, 95% confidence interval [1.10–10.50]) and a time from primary diagnosis (TPD) > 30 months (HR: 0.22 [0.06–0.82]) were independent prognostic factors of OS. The 1 and 2 years PFS were 66.8% and 30.9% with a median PFS time of 18 months [13–24]. The one- and two-years BPI were 27.7% and 55.3%. In multivariate analysis, unfavorable histology was associated with worse BPI (HR: 3.19 [1.32–7.76]). The SRE-FS was 93.3% and 78.5% % at 1 and 2 years. The overall response rate for pain was 75% in the evaluable patients (9/12). No grade ≥ 3 toxicity nor especially no radiation induced myelopathy (RIM), two patients developed asymptomatic vertebral compression fractures.ConclusionThe sole use of SBRT or its association with CFRT is an efficient and well-tolerated treatment that allows high LC for bone oligometastases.     

Influence of comorbidity,age and performance status on treatment efficacy and safety of cetuximab plus irinotecan in irinotecan-refractory elderly patients with metastatic colorectal cancer

BackgroundWe investigated the influence of comorbidity, Eastern Cooperative Oncology Group (ECOG) performance status and age on the efficacy and safety profile of cetuximab and irinotecan in elderly irinotecan-pretreated patients with mCRC.Methods497 patients with mCRC were entered in the database of this non-interventional study (NIS). Comorbid conditions were recorded.ResultsA total of 247 and 250 patients aged <65 and >65 years, respectively, with a median age of 66 y were documented; 78% of the patients showed a reduced ECOG status. Grade III/IV toxicities occurred in 18% of patients without any difference between age groups although older patients had more comorbidities with a higher Charlson Comorbidity Index (CCI) (p = 0.002). Skin rash was strongly related to response (p = 0.006). Age, line of therapy, ECOG, gender and CCI had no influence on response. The objective response rates were similar: 38.1% for age <65 years versus 36.4% for age >65 years (p = 0.57). Progression-free survival (PFS) did not differ between patients 18–65 years (6.0 months) and patients >65 years (6.2 months; p = 0.99). Only PS had a negative impact on PFS (hazard ratio (HR): 0,499; 95% confidence interval (CI) 0.34–0.72; p = 0.002), whereas the presence of skin toxicity (grade > 1) influenced PFS and response rate (RR) positively (HR: 2.04; 95% CI, 1.6–2.6; p < 0.001).ConclusionsOnly PS and age had a negative influence on PFS irrespective of CCI or age. There were no significant differences in response rate and safety profile for elderly patients when treated with cetuximab and irinotecan. Comorbidities and age had no influence on efficacy or toxicity.     

Primary cardiac sarcomas: A retrospective study of the French Sarcoma Group

IntroductionPrimary cardiac sarcomas (PCS) are rare tumours of dismal prognosis.MethodsData of 124 patients with PCS referred to institutions of the French Sarcoma Group (FSG) from 1977 and 2010 were reviewed.ResultsMedian age was 48.8 years. PCS were poorly-differentiated sarcomas (N = 45, 36.3%), angiosarcomas (N = 40, 32.3%), leiomyosarcomas (N = 16, 12.9%) and others (N = 23, 18.6%). At diagnosis, 100 patients (80.6%) were localised and 24 (19.4%) metastatic. Tumours were located in the right (N = 47, 38.8%), left atrial cavities (N = 45, 37.2%) or encompassed several locations in nine cases (7.4%). Surgery was performed in 81 cases (65.3%). Heart transplant was performed in five patients. Radiotherapy adjuvant (N = 18, 14.5%) or alone (N = 6, 4.8%) was performed in non-metastatic patients only (N = 24, 19.4%). With a median follow-up of 51.2 months, median overall survival (OS) was 17.2 months for the entire cohort, 38.8 months after complete resection versus 18.2 after incomplete resection and 11.2 months in non-resected patients. Radiotherapy was associated with improved progression-free survival (PFS) on multivariate analysis. Chemotherapy was significantly associated with better OS only in non-operated patients but not in operated patients. In non-metastatic patients, surgery (hazard ratio [HR] = 0.42, p < 0.001), male gender (HR = 0.56, p = .032) was associated with better OS and surgery (HR = 0.61; p = .076), radiotherapy (HR = 0.43; p = .004) and chemotherapy (HR = 0.30, p = .003) improved PFS.ConclusionOnly surgical resection is associated with a perspective of prolonged survival. Chemotherapy is associated with a better outcome in non-resected patients.     

Postprogression survival for first-line chemotherapy in patients with advanced gastric cancer

BackgroundWith the increasing availability of active agents, the importance of postprogression survival (PPS) has been recognised for several malignancies. However, little is known of PPS in advanced gastric cancer.Patients and methodsA literature search identified 43 randomised trials in chemotherapy-naive patients with advanced gastric cancer. We partitioned overall survival (OS) into progression-free survival (PFS) and PPS, and then examined the correlation between median OS and either median PFS or median PPS. The correlation between differences in OS (ΔOS) and those in PFS (ΔPFS) between trial arms was also investigated.ResultsThe average median OS was significantly longer in recent (2006 and later) trials than in older (2005 and earlier) trials (10.60 versus 8.64 months, P < 0.001), as was the average median PPS (5.34 versus 3.74 months, P = 0.001). Median PPS was correlated with median OS for all trials (r = 0.732), and this correlation was more pronounced in recent trials (r = 0.850). By contrast, the correlation between median PFS and median OS was less pronounced in recent trials (r = 0.282), as was that between ΔPFS and ΔOS (r = 0.365).ConclusionAn increase in median PPS was found in accordance with an increase in median OS in recent trials compared with older trials for patients with advanced gastric cancer.     

Improved overall survival after implementation of targeted therapy for patients with metastatic renal cell carcinoma: Results from the Danish Renal Cancer Group (DARENCA) study-2

AimTo evaluate the implementation of targeted therapy on overall survival (OS) in a complete national cohort of patients with metastatic renal cell carcinoma (mRCC).MethodsAll Danish patients with mRCC referred for first line treatment with immunotherapy, TKIs or mTOR-inhibitors between 2006 and 2010 were included. Baseline and outcome data were collected retrospectively. Prognostics factors were identified using log-rank tests and Cox proportional hazard model. Differences in distributions were tested with the Chi-square test.Results1049 patients were referred; 744 patients received first line treatment. From 2006 to 2010 we observed a significant increase in the number of referred patients; a significant increase in treated patients (64% versus 75%, P = 0.0188); a significant increase in first line targeted therapy (22% versus 75%, P < 0.0001); a significant increase in second line treatment (20% versus 40%, P = 0.0104), a significant increased median OS (11.5 versus 17.2 months, P = 0.0435) whereas survival for untreated patients remained unchanged. Multivariate analysis validated known prognostic factors. Moreover, treatment start years 2008 (HR 0.74, 95% CI, 0.55–0.99; P = 0.0415), 2009 (HR 0.72, 95% CI, 0.54–0.96; P = 0.0277) and 2010 (HR 0.63, 95% CI, 0.47–0.86; P = 0.0035) compared to 2006, and more than two treatment lines received for patients with performance status 0–1 (HR 0.76, 95% CI, 0.58–0.99; P = 0.0397) and performance status 2–3 (HR 0.19, 95% CI, 0.06–0.60; P = 0.0051) were significantly associated with longer OS.ConclusionThis retrospective study documents that the implementation of targeted therapy has resulted in significantly improved treatment rates and overall survival in a complete national cohort of treated mRCC patients.     

The value of C-reactive protein and comorbidity in predicting survival of patients with high grade soft tissue sarcoma

BackgroundThe aim of this study was to determine whether C-reactive protein (CRP) levels or patient’s comorbidity before treatment predicted the overall disease-specific survival and local tumour control in high grade soft tissue sarcoma patients.MethodsA total of 332 primary adult soft tissue sarcoma patients were retrospectively reviewed. CRP levels were obtained prior to treatment for all patients. The Charlson comorbidity index (CCI) was used for evaluation as a measure of comorbidity. Patients that presented with metastases at diagnosis were excluded from this study.ResultsElevated CRP levels were seen in 152 patients. CCI score varied from 0 to 4. Two-hundred and sixty-five patients had a score of 0 (no identified comorbidity), and 67 patients had a score of 1 or more. Patients with elevated CRP levels prior to initial treatment had a poorer disease-specific survival (42% at 5 years) than patients with normal CRP levels (82% at 5 years) (p < 0.0001). Patients with elevated CRP levels had a poorer local recurrence-free rate after initial treatment (75% at 5 years) than patients with normal CRP levels (89% at 5 years) (p = 0.0004). Multivariate analysis also showed the preoperative CRP level to be an independent predictor of survival and local control. Although age in patients with identified comorbidity was significantly higher than those in patients with no-identified comorbidity, CCI was not a predictive factor for either survival or local control.ConclusionPretreatment elevated CRP levels were found to be a poor prognostic factor for disease-specific survival and local control for soft tissue sarcoma patients.     

Low- and high-grade esthesioneuroblastomas display a distinct natural history and outcome

PurposeEsthesioneuroblastomas, also called olfactory neuroblastomas (ENB) represent a rare sinonasal neurectodermal tumour which prognostic factors are unsteadily described.Patients and methodsClinical and pathological characteristics were analysed in patients treated at Gustave Roussy Institute between 1979 and 2009.ResultsOut of 63 patients, 19 patients were reclassified and 44 patients were eligible for the analysis. Multivariate analysis revealed that T staging of the modified Dulguerov TNM staging and Hyams grade > III (that we termed high-grade ENB) were the only independent prognostic factors for overall survival (OS). As compared to patients with low-grade ENB (Hyams grade ? III), patients with high-grade ENB have higher T4 staging (p = 0.02), have frequent lymph node involvement (p = 0.009) and are more often unresectable (p = 0.005). Resected patients with high-grade ENB frequently displayed mainly leptomeningeal metastasis (n = 4/6) in contrast to patients with low-grade ENB who typically experience late loco-regional recurrence (n = 10/25). With a median follow-up of 9.6 years, median DFS and OS for resected low-grade ENB were 5.4 and 20.5 years, respectively. Conversely, median DFS and OS for high-grade ENB were 1.5 and 2.5 years, respectively.ConclusionLow and high-grade ENB display distinct patterns at presentation and relapse, leading to different prognosis. Therefore, they may be regarded as distinct entities.     

Isolated loco-regional recurrence after radical nephrectomy for renal cell carcinoma: A study of 22 patients

ObjectiveThis study aimed to assess prognosis of isolated local recurrence (ILR) of renal cell carcinoma (RCC) after radical nephrectomy (RN).Patients and MethodsThis retrospective study involved 22 cases (16 men and 6 women) of ILR from two centers with a mean age of 60.1 ± 8.5 years. All cases were managed surgically.ResultsPrimary tumors were mainly clear cell carcinoma (n = 17). Nine patients had T3 and T4 tumors. Local recurrence involved mainly the operative bed (n = 17); 4 among them had nodal recurrence as well. The median interval to local recurrence was 13.5 months (7–25 months). Stages T3 and T4 were significantly associated with shorter interval. Complete excision was possible in 9 patients (41%); 8 tumors were irresectable. It was associated with significantly higher overall and median disease-free survival (DFS). Advanced disease stage (p = 0.002) and shorter interval to recurrence (p < 0.001) were associated with higher proportion of incomplete excision. The median overall survival and DFS were 15 months (95% CI: 4.4–25.6) and 10 months (95% CI: 4.5–15.5), respectively. Overall and DF survival were significantly better in patients with nodal recurrence only, complete excision of the recurrence and interval from nephrectomy to recurrence >15 months.ConclusionILR after radical nephrectomy for RCC is more common with more advanced stages, where interval to recurrence tends to be shorter. The management should be surgical, which was possible in nearly 60% of cases. Complete excision was associated with better overall and disease free survival.     

Metastatic medulloblastoma in adults: Outcome of patients treated according to the HIT2000 protocol

BackgroundDue to the rarity of metastatic medulloblastoma in adults, knowledge about the efficacy and toxicity of intensified chemotherapy and radiotherapy is limited.Patients and methodsAdults with disseminated medulloblastoma registered in the HIT2000 trial as observational patients and treated according to one of two different treatment regimens were analysed. The sandwich strategy MET-HIT2000AB4 consists of postoperative chemotherapy, hyperfractionated craniospinal radiotherapy, and maintenance chemotherapy; while the HIT′91 maintenance strategy consists of postoperative craniospinal radiotherapy, and maintenance chemotherapy.ResultsTwenty-three patients (median age: 30.7 years), diagnosed from November 2001 to July 2009, and treated in 18 institutions in Germany and Austria, were eligible. The median follow-up of surviving patients was 3.99 years. The 4-year event-free survival (EFS) and overall survival (OS) ± standard error (SE) were 52% ± 12% and 91% ± 6%, respectively. The survival was similar in both treatment groups (HIT′91 maintenance strategy, n = 9; MET-HIT2000AB4 sandwich strategy, n = 14). Patients with large cell/anaplastic medulloblastoma relapsed and died (n = 2; 4-year EFS/OS: 0%) and OS differed compared to patients with classic (n = 11; 4-year EFS/OS: 71%/91%) and desmoplastic medulloblastoma (n = 10; 4-year EFS/OS: 48%/100%), respectively (p = 0.161 for EFS and p = 0.033 for OS).Treatment-induced toxicities consisted mainly of neurotoxicity (50% of patients, ⩾ °II), followed by haematotoxicity and nephrotoxicity/ototoxicity. The professional outcome appeared to be negatively affected in the majority of evaluable patients (9/10).ConclusionsTreatment of adults with metastatic medulloblastoma according to the intensified paediatric HIT2000 protocol was feasible with acceptable toxicities. EFS rates achieved by both chemotherapeutic protocols were favourable and appear to be inferior to those obtained in older children/adolescents with metastatic disease.     

The role of postoperative radiotherapy (PORT) in pulmonary large cell neuroendocrine carcinoma (PLCNEC)

PurposeTo assess the long-term survivals and related prognostic indicators of patients with pulmonary large cell neuroendocrine carcinoma (PLCNEC), and determine the prognostic value of post-operative radiotherapy in PLCNEC.Materials and methodsPatients diagnosed with PLCNEC between 2004 and 2015 from the Surveillance, Epidemiology, and End Results (SEER) database were included in our study. Cox proportional hazard model was used to evaluate the factors related to overall survival (OS). Propensity score matching analysis (PSM analysis) was used to balance the variables differences between postoperative radiotherapy (PORT) and non-PORT groups.ResultsA total of 701 postoperative cases were identified, with the median follow-up time of 23 months. The 3- and 5-year OS were 50.7%, and 41.2%, respectively. Multivariate analysis revealed that stage I (P < 0.001), age < 65 years old (P < 0.001), chemotherapy (P < 0.001) were independent favorable prognostic factors. There is no significant difference in survival between patients with or without postoperative radiotherapy (PORT) after PSM analysis (P = 0.489). No survival benefit in favor of PORT were displayed, even when subgroups were deeply analyzed.ConclusionsAge, stage, and chemotherapy were significantly associated with OS of patients with resected PLCNEC. However, PORT after resection did not improve long-term outcome of PLCNEC patients.     

Efficacité et tolérance de la radiothérapie externe pour les patients atteints d'une récidive d'un carcinome différencié de la thyroïde

PurposeRadiation therapy is often the last resource treatment for cervical relapse in iodine refractory differentiated thyroid cancer. We present locoregional control data in patients with cervical relapse treated with curative intent radiation therapy with or without concomitant carboplatin.Material and methodsThis monocentric retrospective study gathered data on patients with differentiated thyroid carcinoma – vesicular or papillary – in relapse after thyroidectomy who received a curative intent cervical radiation therapy. Locoregional progression free survival (LRPFS), progression free survival (PFS), overall survival (OS) were gathered as well as acute and chronic adverse events assessed with the CTCAE v4.ResultsThirty-nine patients were consecutively included between 2005 and 2019. The median follow-up was 36.6 months. Fifteen patients (38%) had a locoregional relapse, locoregional control at 2 years was 66.7%. The median LRPFS was 48 months [32.9–not reached] and the median overall survival 49 months [38.8–not reached]. In multivariate analysis, initial incomplete resection was associated with poorer OS (HR: 24.39 [3.57–166.78], P = 0.00113) and LRPFS (HR: 33.91 [4.46–257.61], P = 0.00066), extra nodal spread was associated with poorer LRPFS (HR: 13.45 [1.81–99,76], P = 0.011). ECOG performance status was associated with OS (HR: 5.11 [1.57–16.66], P = 0.00688). Carboplatin association with radiation therapy was not associated with improved survivals (OS: P = 0.34, LRPFS: P = 0.84). The rate of acute grade 3 toxicities was 14%.ConclusionSalvage cervical radiation therapy was associated with a locoregional control of 66.7% at 2 years with a reasonable toxicity rate. Carboplatin association with radiation therapy did not improve locoregional control nor overall survival in comparison with radiotherapy alone.     

The prognostic significance of minimal residual disease in adult Egyptian patients with precursor acute lymphoblastic leukemia

BackgroundMinimal residual disease (MRD) studies in adult acute lymphoblastic leukemia (ALL) give highly significant prognostic information superior to other standard criteria as age, gender and total leucocytic count (TLC) in distinguishing patients at high and low risk of relapse.ObjectivesWe aimed to determine the value of MRD monitoring by flowcytometry (FCM) in predicting outcome in adult Precursor ALL patients.Patients and methodsBone marrow (BM) samples were analyzed by 4-color FCM collected at diagnosis and after induction therapy (MRD1) to correlate MRD positivity with disease free survival (DFS) and overall survival (OS).ResultsStudy included 57 adult ALL patients (44 males and 13 females) with a median age of 22 years (18–49). DFS showed no significant difference with age, gender and initial TLC (p = 0.838, 0.888 and 0.743, respectively). Cumulative DFS at 2 years was 34% for B-lineage ALL (n: 35) and 57% for T-lineage ALL (n: 18) (p = 0.057). Cumulative DFS at 2 years was 7% for MRD1 positive (high risk, HR) versus 57% for MRD1 negative patients (Low risk, LR) (p < 0.001). Cumulative DFS at 2 years was 29% for HR patients (n: 26) versus 55% for LR (n: 27) according to GMALL classification (p = 0.064). Cumulative OS did not differ according to age, gender and TLC (p = 0.526, 0.594 and 0.513, respectively). Cumulative OS at 2 years was 36% for B ALL (n: 39) versus 77% for TALL (n: 18) (p = 0.016) and was 49% for Philadelphia chromosome (Ph) negative patients versus 0% for Ph-positive patients (p < 0.001). Regarding MRD1, OS at 2 years was 18% for MRD1 HR (n: 17) versus 65% for MRD1 LR (n: 38) (p < 0.001). OS was 35% for high-risk patients (n: 30) and 62% for low-risk patients (n: 27) classified according to GMALL risk stratification (p = 0.017).ConclusionMRD by FCM is a strong independent predictor of outcome in terms of DFS and OS and is a powerful informative parameter in guiding individual treatment in ALL patients.     

The impact of phosphorylated AMP-activated protein kinase expression on lung cancer survival

BackgroundThe aim of this study is to investigate the prognostic role of phosphorylated AMP-activated protein kinase (pAMPK) in surgically resected non-small-cell lung cancer (NSCLC).MethodsImmunohistochemical staining of pAMPK was carried out on tissue microarrays containing 463 samples obtained from patients with NSCLC and correlated with clinicopathological characteristics and survival.ResultspAMPK expression levels were significantly higher in never smokers versus former smokers versus current smokers (P = 0.045). A positive pAMPK expression was associated with increased overall survival (OS) and recurrence-free survival (RFS) (P = 0.0009 and P = 0.0007, respectively). OS and RFS were statistically superior in pAMPK-positive than in pAMPK-negative patients with adenocarcinoma (ADC; median OS: 5.6 and 4.2 years, respectively, P = 0.0001; median RFS: 5.0 and 2.4 years, respectively, P = 0.001), whereas they were similar in those patients with squamous cell carcinoma. Multivariate analysis confirmed that pAMPK positivity was associated with OS [hazard ratio (HR) = 0.574, 95% confidence interval (CI) 0.418–0.789, P = 0.0006) and RFS (HR = 0.608, 95% CI 0.459–0.807, and P = 0.0006), independent of clinical covariates.ConclusionsHigh pAMPK expression levels are associated with increased survival in patients with NSCLC, especially those with ADC. Our results support further evaluation of AMP-activated protein kinase as a potential prognostic and therapeutic target for lung cancer.     

Multimodality therapy improves survival in elderly patients with locally advanced non-small cell lung cancer—A retrospective analysis

ObjectivesConcurrent combined modality therapy is optimal treatment for patients with stage III non-small cell lung cancer (NSCLC) and is given with curative intent. However, elderly patients (≥ 75) are often undertreated, despite good performance status (PS). This study evaluated the treatment, outcomes and survival in elderly patients with stage III NSCLC versus patients < 75 years old.Materials and MethodsA retrospective review of data from the Lung Cancer Registry at Mayo Clinic Arizona (MCA) was conducted. Patients with newly diagnosed stage III NSCLC from 1998 to 2006 were analyzed for type of therapy and outcomes.ResultsThree hundred and eighty-nine patients with newly diagnosed stage III NSCLC were identified from 1998 to 2006. Two hundred and forty-three (62%) patients were < 75 years old, and 146 patients (38%) were ≥ 75 years old. Among 374 eligible patients, 45% of patients < 75 years old received combined chemoradiation therapy vs. only 21% of patients ≥ 75 years old (p < 0.0001). The median survival in the < 75 age group was 14.5 months vs. 10.1 months in the ≥ 75 age group (p = 0.0014). In the < 75 age group, median survival was 15.0 months in patients who received combined modality treatment vs. 14.1 months in the other treatments group (p = 0.02). In the elderly group, median survival was 19.9 months in the combined modality group vs. 7.8 months in the other treatments group (p = 0.0048).ConclusionOur results confirm that older patients are less likely to receive optimal therapy, regardless of functional status. Prospective studies are desperately needed to help improve management of the burgeoning geriatric oncology population.