Characteristics of long-term survivors of brain metastases from lung cancer

Background and aim

Long-term survival of lung cancer patients with brain metastases (BM) is very rare. Our aim is to report the characteristics of patients who survived for at least three years after a BM diagnosis.

Materials and methods

Nineteen lung cancer patients who had survived ≥3 years after a BM diagnosis were identified in our database. Seven (37%) had undergone whole-brain radiotherapy (WBRT) only, five (26%) BM surgery + WBRT, three (16%) BM surgery + WBRT + BM radiosurgery, and four (21%) no WBRT (one, surgery; one, radiosurgery; two, BM surgery + radiosurgery). Their characteristics were compared with historical data for 322 lung cancer patients with BM (control group, CG), who had received WBRT between 1986 and 1997.

Results

Median survival from BM in long survivors group was 73 months (in CG – 4 months). Characteristics comparison: median age 55 vs. 58 (CG), p = 0.16; female sex 68% vs. 28% (CG), p = 0.003; RTOG/RPA class 1 – 75% vs. 13% (CG), p = 0.00001; adenocarcinoma histology 84% vs. 24% (CG), p < 0.00001; control of primary tumor 95% vs. 27% (CG), p < 0.00001; extracranial metastases 0 vs. 26% (CG), p = 0.01; single BM 63% vs. 9% (CG), p = 0.00001; surgery of BM 53% vs. 14% (CG), p = 0.00001.

Conclusions

Beside prognostic factors already recognized as favorable in patients with BM, the adenocarcinoma histology and female sex were prevalent in long-term survivors of BM from lung cancer.     

Fine-Needle Aspirates CYFRA 21-1 is a Useful Tumor Marker for Detecting Axillary Lymph Node Metastasis in Breast Cancer Patients

Introduction

To assess whether the value of CYFRA21-1 in the aspirates of ultrasonography-guided fine-needle aspiration biopsy (US-FNAB) can contribute to improving the performances of US-FNAB in the diagnosis of axillary lymph node (LN) metastasis in breast cancer patients.

Methods

US-FNAB was performed in 156 axillary LNs in 152 breast cancer patients (mean age: 51.4 years, range: 17–92 years). Concentrations of CYFRA21-1 were measured from washouts of the syringe used during US-FNAB. Tumor marker concentrations, US-FNAB, intraoperative sentinel node biopsy (SNB), and surgical pathology results were reviewed and analyzed. For comparison, the values of CEA and CA15-3 were also measured from washouts.

Results

Among the 156 LNs, 75 (48.1%) were benign, and 81 (51.9%) were metastases. Mean concentrations of CYFRA21-1 were significantly higher in metastasis compared to benign LNs (P<0.001). US-FNAB combined to CYFRA21-1 showed significantly higher sensitivity, NPV, and accuracy compared to US-FNAB alone (all values P<0.05). All diagnostic indices of US-FNAB combined to CYFRA21-1 were significantly higher compared to US-FNAB combined with CEA or CA15-3 (all P<0.001). Of the 28 metastatic LNs which showed metastasis on SNB, CYFRA21-1 showed higher positive rate of 75.0% (CEA or CA15-3∶60.7%, P = 0.076).

Conclusion

Measuring CYFRA 21-1 concentrations from US-FNAB aspirates improves sensitivity, NPV, and accuracy of US-FNAB alone, and may contribute to reducing up to 75.0% of unnecessary intraoperative SNB. Compared to CEA or CA15-3, CYFRA21-1 shows significantly higher performances when combined to US-FNAB in the preoperative diagnosis of LN metastasis in breast cancer patients.     

Tamoxifen in breast cancer ipse dixit in uterine malignant mixed Müllerian tumor and sarcoma—A report of 8 cases and review of the literature

Aim

Report the outcome of 8 patients (pts) with breast cancer (BC) treated with Tamoxifen (TAM) that developed malignant mixed Müllerian tumor (MMMT) and rare uterine sarcoma (RUS).

Patients and methods

Retrospective study based on data collected from the department medical records between April 1999 and September 2010 among 583 pts with endometrial cancer, 36 pts with MMMT and RUS histopathology. Among them, 8 pts underwent TAM between 4 and 10 years due to a previous diagnosis of BC; all pts were post-menopausal with regular gynecological surveillance; 6 pts (75%) with abnormal uterine bleeding. The diagnosis of 6 pts (MMMT) and 2 pts (RUS) occurred at median interval of 8 years (range 4–12) after initial BC treatment. Pts underwent surgical treatment and were staged as stage I (3pts), IIIA (3pts) and IIIC (2 pts) (FIGO 1988); followed by whole pelvis irradiation (50 Gy) and intracavitary HDR brachytherapy boost (24 Gy). Two pts underwent chemotherapy (CT). Overall and disease free survival was calculated by Kaplan Meier method.

Results

With a median follow-up of 47 months (range 17–130), 3 pts remain alive recurrence-free of BC and RUS. Four pts died with distant metastasis within the first follow-up year, without BC. One pt died from non-related cancer cause. No evidence of local recurrence was found in the whole group of pts. At two years, DFS and OS were 40% and 80%, respectively.

Conclusion

As reported in the literature, TAM administration and causal effect on MMMT and RUS in BC pts is still unknown. No reports about outcome from these specific pts were found.     

Bone Disease in Newly Diagnosed Lupus Nephritis Patients

Introduction

Bone loss in Lupus Nephritis (LN) patients is common and multifactorial. The aim of this study was to evaluate the bone status of newly diagnosed LN patients and their correlation with inflammatory factors involved in LN physiopathology.

Methods

We studied 15 pre-menopausal patients with ≤2 months of diagnosed SLE and LN. Patients with prior kidney or bone disease were excluded. In addition to biochemical evaluation (including 25-hydroxyvitamin D₃ [25(OH)D] and Monocyte Chemotactic Protein (MCP1) dosage), we performed bone biopsies followed by osteoblast culture, histomorphometric and immunohistochemistry analysis.

Results

LN patients presented a mean age of 29.5±10 years, a proteinuria of 4.7±2.9 g/day and an estimated glomerular filtration rate (GFR) of 37(31–87) ml/min/1,73 m². They were on glucocorticoid therapy for 34±12 days. All patients presented vitamin D insufficiency (9.9±4.4 ng/ml, range 4–20). Urinary MCP1 correlated negatively with 25(OH)D (r = −0.53, p = 0.003) and positively with serum deoxypyridinoline (r = 0.53, p = 0.004). Osteoblasts isolated from LN bone biopsies presented a significantly higher expression of MCP-1 when compared to controls (32.0.±9.1 vs. 22.9±5.3 mean fluorescence intensities, p = 0.01). LN patients presented a significantly reduced osteoid volume, osteoid thickness, osteoid surface, mineralization surface and bone formation rate, associated with an increased eroded surface and osteoclast surface. Patient’s bone specimens demonstrated a reduced immunostaining for osteoprotegerin (0.61±0.82 vs. 1.08±0.50%, p = 0.003), and an increased expression of Receptor Activator of NF-κB ligand (RANKL) (1.76±0.92 vs. 0.41±0.28%, p<0.001) when compared to controls.

Discussion

Newly diagnosed LN patients presented a significant disturbance in bone metabolism, characterized by an impaired bone formation and mineralization, associated with an increase in resorption parameters. Glucocorticoid use, vitamin D insufficiency and inflammation might be involved in the physiopathology of bone metabolism disturbance.     

Toxicity outcome in patients treated with modulated arc radiotherapy for localized prostate cancer

Aim

This study evaluates the acute toxicity outcome in patients treated with RapidArc for localized prostate cancer.

Background

Modern technologies allow the delivery of high doses to the prostate while lowering the dose to the neighbouring organs at risk. Whether this dosimetric advantage translates into clinical benefit is not well known.

Materials and methods

Between December 2009 and May 2012, 45 patients with primary prostate adenocarcinoma were treated using RapidArc. All patients received 1.8 Gy per fraction, the median dose to the prostate gland, seminal vesicles, pelvic lymph nodes and surgical bed was 80 Gy (range, 77.4–81 Gy), 50.4 Gy, 50.4 Gy and 77.4 Gy (range, 75.6–79.2 Gy), respectively.

Results

The time between the last session and the last treatment follow up was a median of 10 months (range, 3–24 months). The incidence of grade 3 acute gastrointestinal (GI) and genitourinary (GU) toxicity was 2.2% and 15.5%, respectively. Grade 2 acute GI and GU toxicity occurred in 30% and 27% of patients, respectively. No grade 4 acute GI and GU toxicity were observed. Older patients (>median) or patients with V60 higher than 35% had significantly higher rates of grade ≥2 acute GI toxicity compared with the younger ones.

Conclusions

RapidArc in the treatment of localized prostate cancer is tolerated well with no Grade >3 GI and GU toxicities. Older patients or patients with higher V60 had significantly higher rates of grade ≥2 acute GI toxicity. Further research is necessary to assess definitive late toxicity and tumour control outcome.     

Unintended irradiation of internal mammary chain – Is that enough?

Aim

To evaluate the unintentional coverage of the internal mammary chain (IMC) with tangential fields irradiation to the breast, and its relation with the type of surgery employed.

Background

The dose distribution in regions adjacent to the treatment targets (mammary gland or chest wall), with incidental irradiation of the IMC, could translate into clinical benefit, due to the proximity of these regions.

Materials and methods

One hundred and twelve consecutive conformal radiotherapy plans were correlating the average dose to the IMC with the type of surgery employed, the extent of disease and the irradiation techniques.

Results

The mean doses to IMC after modified radical mastectomy (MRM), modified radical mastectomy with immediate reconstruction (MRM + R), and breast conservative surgery (BCS) were 30.34 Gy, 30.26 Gy, and 18.67 Gy, respectively. Significant differences were identified between patients who underwent MRM or MRM + R over BCS (p = 0.01 and 0.003, respectively), but not between MRM and MRM + R (p = 0.88). Mean doses to IMC were greater in patients with T3–T4 tumors when compared with more initial stages (≤T2) (p = 0.0096). The lymph node involvement also correlated with higher average doses to IMC (node positive: 26.1 Gy × node negative: 17.8 Gy, p = 0.0017).

Conclusions

The moderate dose level to the IMC in the unintentional irradiation scenario seems to be insufficient to treat the subclinical disease, although it could have an impact in patients undergoing mastectomy.     

Postoperative radiotherapy in prostate cancer: Analysis of prognostic factors in a series of 282 patients

Aim

To assess the outcomes of patients treated with postoperative RT in relation to the possible prognostic factors.

Background

Postoperative radiotherapy (RT) has been proved to reduce the risk of biochemical recurrence in high-risk prostate cancer patients. Baseline prostate specific antigen (PSA), pathological Gleason score (GS), positive surgical margins, nodal status and seminal vesicle invasion are independent predictors of biochemical relapse.

Materials and methods

The clinical records of 282 patients who underwent postoperative RT were retrospectively reviewed. The prognostic value of postoperative PSA, preoperative risk class, nodal status, pathological GS, margins status, and administration of hormonal therapy (HT) was analyzed.

Results

Postoperative RT was delivered with a median dose to the prostatic fossa of 66 Gy (range 50–72) in 1.8–2 Gy/fraction. Median follow-up was 23.1 months (range 6–119). Five-year actuarial biochemical disease-free survival (bDFS) and overall survival rates were 76% and 95%, respectively. Higher bDFS was found for patients with postoperative PSA <0.02 ng/ml (p = 0.03), low preoperative risk class (p = 0.01), pN0 (p = 0.003), GS 4–6 (p = 0.0006), no androgen deprivation therapy (p = 0.02), and irrespective of surgical margin status (p = 0.10). Multivariate analysis showed that postoperative PSA and Gleason score had a significant impact on bDFS (p = 0.039 and p = 0.05, respectively).

Conclusions

Postoperative RT with a dose of 66 Gy offers an acceptable toxicity and an optimal disease control after radical prostatectomy in patients with different risk features. A postoperative PSA >0.02 ng/ml could be considered as a prognostic factor and a tool to select patients at risk for progression.     

Dependence of the safe rectum dose on the CTV–PTV margin size and treatment technique

Background

Late rectal injury is a common side effect of external beam radiotherapy for prostate cancer.

Aim

The aim of this study was to evaluate what total dose may be safely delivered for prostate patients for 3DCRT and IMRT techniques and the CTV–PTV margin.

Materials and methods

3DCRT and IMRT plans were prepared for 12 patients. For each patient PTV was defined with CTV–PTV margins of 0.4, 0.6, …, 1.0 cm, and total doses of 70, 72, …, 80 Gy, with 2 Gy dose fraction. NTCP values for the rectum were calculated using the Lyman model. Both techniques were compared in terms of population mean DVH.

Results

Significantly smaller NTCPs for IMRT were obtained. For both techniques diminishing the margin CTV–PTV of 2 mm leads to decreasing the NTCP of about 0.03. For total dose of 80 Gy the NTCP was smaller than 10% for the 4 mm margin only. The QUANTEC dose volume constraints were more frequently fulfilled for the IMRT technique than for the 3DCRT technique.

Conclusions

The IMRT technique is safer for prostate patients than the 3DCRT. If very high total doses are applied the CTV–PTV margin of 0.4 cm and the IMRT technique should be used. If the CTV–PTV margin of 0.6 cm is applied, the NTCP is smaller than 10% for the 3DCRT and IMRT techniques for the total doses smaller than 74 Gy and 78 Gy, respectively.     

A 346 Case Analysis for Laparoscopic Spleen-Preserving No.10 Lymph Node Dissection for Proximal Gastric Cancer: A Single Center Study

Purpose

This study was designed to formulate a model that efficiently predicts splenic hilar lymph node metastasis (SHLNM) in patients with proximal gastric cancer and to assess indications for laparoscopic spleen-preserving no.10 lymph node dissection (LSPNo.10LND) based on this model.

Methods

Patients (N = 346) with proximal gastric cancer who underwent LSPNo.10LND from January 2010 to October 2013 were prospectively enrolled and retrospectively evaluated. Groups of patients with and without SHLNM were compared, and independent risk factors for SHLNM determined. An optimal predictive model of SHLNM in patients with proximal gastric cancer was well established.

Results

Of the 346 patients with proximal gastric cancer, only 35 (10.1%) were diagnosed with SHLNM. Depth of invasion, tumor location and metastases to No.7 and No.11 lymph nodes (LNs) were independent risk factors for SHLNM (p<0.0001 each). A model involving depth of invasion, tumor location and metastasis to No.7 and 11 LNs yielded a lowest Akaike’s information criterion (AIC) of −913.535 and a highest area under the ROC curve (AUC) of 0.897(95%CI:0.851–0.944). Stratification analysis showed no SHLNMs in the absence of serosal invasion of the lesser curvature and metastases at No.7 and No.11 LNs (T2-3∶0/87, 95% CI: 0.00–4.15).

Conclusions

A model including depth of invasion, tumor location and metastases at No.7 and No.11 LNs was found optimal for predicting SHLNM for proximal gastric cancers. LSPNo.10LND may be avoided when tumors on the lesser curvature did not show serosal invasion or metastases at No.7 and No.11 LNs.     

Early closure of phase II prospective study on acute and late tolerance of hypofractionated radiotherapy in low-risk prostate cancer patients

Aim

To assess acute and late toxicity of hypofractionated radiotherapy, its efficacy and impact on quality of life in patients with low-risk prostate cancer.

Materials and methods

Since August 2006 to October 2007, 15 prostate cancer patients with favorable clinical features, aged 54–74 years (mean 67 years) entered the study. Tumor stage in the majority (73%) of patients was T2a, the mean pretreatment PSA value was 7.2 ng/ml (range 5–10.9 ng/ml). The study group was treated 3 times a week with 4 Gy per fraction to the total dose of 60 Gy within 5 weeks. 3D conformal treatment planning was used with no fiducial markers. Acute and late toxicity was evaluated using modified EORTC/RTOG/LENT scoring systems. Patients regularly filled the EORTC QLQ-PR25 questionnaires.

Results

All patients completed radiotherapy according to the plan. During radiotherapy, 26% of patients had grade 1–2 rectal symptoms. The incidence of acute urinary toxicity score was 26%, 60%, and 14% for grade 0–1, 2 and 3, respectively. One year after RT, the incidence of grade 2 GI toxicity was 27%, which was the reason for an early closure of the accrual. Grade 2 late urinary toxicity was noted in 20% of patients. The mean PSA level was 0.61 ng/ml after 24 months and 0.47 ng/ml after 36 months (range: 0.06–1.54 ng/ml).

Conclusions

Low number of patients does not allow to determine the influence of hypofractionation on unsatisfactory tolerance of this regimen. Suboptimal (from the present day''s perspective) target localization (no fiducial markers) could potentially explain higher than expected late GI reactions in our series.     

Impact of neoadjuvant chemoradiation on pathologic response and survival of patients with locally advanced rectal cancer

Background

The impact of neoadjuvant chemotherapy (CT) and radiotherapy (RT) on overall survival (OS) has been controversial. Some studies have pointed to an improvement in OS and disease-free survival (DFS) in patients with pathologic complete response (pCR).

Aim

To evaluate the therapeutic response and impact on survival of preoperative RT, alone or combined with CT, in patients with locally advanced rectal cancer (LARC).

Materials and methods

A set of 132 patients with LARC were treated preoperatively. GROUP 1: RT alone, 19 patients. GROUP 2: RT and concomitant oral CT (Capecitabine or UFT + leucovorin), 68 patients. GROUP 3: RT and concomitant CT with 5-FU in continuous infusion, 45 patients. 58.2% of patients were submitted to adjuvant CT.

Results

GROUP 1: no pCR, tumoral downstaging was 26.7%. GROUP 2: pCR in 16.9%; tumoral downstaging was 47.7%. GROUP 3: pCR in 11.9%; tumor downstaging was 52.4%. The loco-regional control (LRC) was 95%. The 5-year OS (p = 0.038) and DFS (p = 0.05) were significantly superior in patients treated with CT + RT. Patients with pCR had a significant increase on DFS (p = 0.019). Patients cT3–4 that had a tumoral downstaging to ypT0–2, showed an increase on DFS, OS and LRC.

Conclusions

CT combined with RT has increased tumoral response and survival rate. Nodal downstaging and pCR were higher in the GROUP 2. The 5-year OS and DFS were significantly superior in CT + RT arms. Patients with pathologic response showed a better DFS. Adjuvant CT had no impact on LRC, DFS nor on OS.     

Racial differences in the burden of coronary artery calcium and carotid intima media thickness between Blacks and Whites

Background

Identification of racial differences in the burden and correlates of carotid intima media thickness (CIMT) and coronary artery calcium (CAC) may provide the basis for the development of race-specific cardiovascular disease (CVD) risk prediction algorithms.

Methods

In the Heart Strategies Concentrating on Risk Evaluation (Heart SCORE) study, CIMT was measured by carotid ultrasonography in 792 individuals (35 % Black). CIMT >1 mm was considered significant. CAC was quantified by electron beam computed tomography in 776 individuals (46 % Black). CAC was considered significant if the Agatston score was >100. Cross-sectional associations between race, CIMT and CAC were assessed using logistic regression models.

Results

Blacks had greater CIMT (mean difference 0.033 mm, 95 % CI 0.005–0.06 mm; p = 0.02) and 1.5-fold (95 % CI 1.0–2.3) higher odds of having significant CIMT than Whites. Blacks had less CAC than Whites (mean Agatston score difference 66, [11–122]; p = 0.02) and 50 % lower odds of a significant CAC score compared with Whites (0.5 [0.3–0.7]). These associations were virtually unchanged after adjustment for CVD risk factors. Of the novel CVD risk markers assessed, small-dense low-density lipoprotein was independently associated with increased odds of significant CIMT, with the association being similar among Blacks and Whites (odds ratio [95 % CI]: 1.7 [1.2–2.5] and 1.4 [1.0–1.8] per 1-SD higher level, respectively). Interleukin-6 was significantly associated with CAC among Blacks (1.4 [1.0–2.0]).

Conclusion

Black race is independently associated with greater CIMT but less CAC than White race. CVD risk stratification strategies that incorporate these measures of subclinical atherosclerosis should consider race-specific algorithms.

Electronic supplementary material

The online version of this article (doi:10.1007/s12471-014-0610-4) contains supplementary material, which is available to authorized users.     

Measurement and comparison of head scatter factor for 7 MV unflattened (FFF) and 6 MV flattened photon beam using indigenously designed columnar mini phantom

Aim

To measure and compare the head scatter factor for 7 MV unflattened and 6 MV flattened photon beam using a home-made designed mini phantom.

Background

The head scatter factor (Sc) is one of the important parameters for MU calculation. There are multiple factors that influence the Sc values, like accelerator head, flattening filter, primary and secondary collimators.

Materials and methods

A columnar mini phantom was designed as recommended by AAPM Task Group 74 with high and low atomic number material for measurement of head scatter factors at 10 cm and d_max dose water equivalent thickness.

Results

The Sc values measured with high-Z are higher than the low-Z mini phantoms observed for both 6MV-FB and 7MV-UFB photon energies. Sc values of 7MV-UFB photon beams were smaller than those of the 6MV-FB photon beams (0.6–2.2% (Primus), 0.2–1.4% (Artiste) and 0.6–3.7% (Clinac iX (2300CD))) for field sizes ranging from 10 cm × 10 cm to 40 cm × 40 cm. The SSD had no influence on head scatter for both flattened and unflattened beams. The presence of wedge filters influences the Sc values. The collimator exchange effects showed that the opening of the upper jaw increases Sc irrespective of FF and FFF.

Conclusions

There were significant differences in Sc values measured for 6MV-FB and unflattened 7MV-UFB photon beams over the range of field sizes from 10 cm × 10 cm to 40 cm × 04 cm. Different results were obtained for measurements performed with low-Z and high-Z mini phantoms.     

3D conformal hypofractionated radical radiotherapy in early glottic cancer

Aim

The purpose of this study was to evaluate acute and late toxicity and the locoregional control in patients treated with hypofractionated radical radiotherapy 2.25 Gy/fraction/day for early glottic carcinoma.

Materials and methods

A retrospective analysis was performed of 27 patients, stage T1–T2 N0 glottic squamous cell carcinoma, that underwent radical RT from April 2008 to October 2011. The mean age was 64.6 years (range 36–81). Seventeen patients were staged T1a, 3 patients T1b and 7 patients T2. All patients were 3D planned and treated in a 6 MV LINAC, 2.25 Gy/fraction/5 days per week, to a total dose between 63 Gy and 67.5 Gy. Biological Effective Dose (BED (α/β = 10)) ranged from 77.18 Gy to 82.69 Gy and EQD2 from 64.31 Gy to 68.91 Gy. Patients were evaluated in periodic follow-up. Toxicity was evaluated according to RTOG Toxicities Scales.

Results

With a median follow-time of 24.7 months (range 3.6–44.2 months), no evidence of locoregional recurrence was observed. The treatment was well tolerated and no unscheduled interruptions in treatments for toxicity were documented, with the median overall treatment time of 41 days (range 38–48). Only grades 1 and 2 acute toxicity were observed and no evidence of severe late toxicity.

Conclusion

The authors believe that this moderately hypofractionated scheme can provide a good locoregional control for T1–T2 glottic carcinomas with no increase of toxicity. As the limitation of this work is the reduced number of patients and the lack of long term follow-up, the authors hope to update this retrospective study in the future in order to improve the power of the results.     

Vacuum-assisted core-needle biopsy as a diagnostic and therapeutic method in lesions radiologically suspicious of breast fibroadenoma

Background

Treatment of breast fibroadenoma remains a subject of clinical discussion. Recommended methods include clinical observation or surgical excision of the lesion. The procedure involves hospitalisation and anaesthesia, leaving a scar on the breast.

Aim

The aim of this study was to present the Centre''s experience in removing lesions radiologically suspicious of fibroadenoma by means of an ultrasound-guided vacuum-assisted core-needle biopsy as an alternative to a classical surgery.

Materials and methods

Between March 2007 and April 2010, 196 ultrasound-guided vacuum-assisted biopsies were performed in the Mammotome Biopsy Laboratory of the 1st Surgical Oncology and General Surgery Department at the Greater Poland Cancer Centre in Poznań. The procedure was delivered to female patients aged 17–91 years (mean 40.8, median 39). Qualified for removal were ultrasound identified lesions described as fibroadenomas.

Results

The average size of excised lesions according to pre-biopsy ultrasound image was 13.53 ± 8.92 mm (median 11 mm, range 4–60 mm). In 184 cases (93.9%), benign lesions were found in the final histopathologic examination. Pre-cancer lesions were found in 10 cases, and invasive lesions in two cases. Overall, after follow-up ultrasound examination, four patients were qualified for subsequent surgical resection of lesions that had been left behind.

Conclusion

Vacuum core-needle biopsy is an effective tool enabling removal of breast fibroadenomas. It combines features of a lesion resection and histopathologic material collection providing an access with minimum invasiveness.     

High levels of memory B cells are associated with response to a first tumor necrosis factor inhibitor in patients with rheumatoid arthritis in a longitudinal prospective study

Introduction

Tumor necrosis factor inhibitor (TNFi) therapy is effective for rheumatoid arthritis (RA). Some researchers have suggested that TNFi therapy affects B-cell homeostasis. We studied the effect of TNFi therapy on the distribution of peripheral B-cell subsets to elucidate B-cell–related biomarkers to predict the TNFi response.

Methods

Peripheral B cells were analyzed for expression of CD19, CD27, CD38 and immunoglobulin D in 31 healthy donors and 96 RA patients, including 21 patients who were followed 3 months after TNFi initiation.

Results

Treatment with steroids significantly altered the distribution of B-cell subsets. After we adjusted for age, sex and steroid dose, we found that patients with RA had B-cell subset proportions similar to controls. B-cell subset distributions did not differ upon use of TNFi at baseline or before or after TNFi introduction. TNFi responders (according to European League Against Rheumatism criteria) at 3 months had significantly higher proportions of CD27⁺ memory B cells at baseline, and ≥26% CD27⁺ cells at inclusion was associated with a relative risk of 4.9 (1.3 to 18.6) for response to TNFi treatment. CD27⁺ cells produced three times more TNFα than did TNFi-naïve B cells and were correlated with interferon γ produced from CD4⁺ cells in patients without TNFi treatment.

Conclusions

In patients with RA, high levels of baseline memory B cells were associated with response to TNFi, which may be related to TNFα-dependent activation of the T helper type 1 cell pathway.     

Late rectal and bladder toxicity following radiation therapy for prostate cancer: Predictive factors and treatment results

Aim

This study aimed at investigating factors associated to late rectal and bladder toxicity following radiation therapy and the effectiveness of Hyperbaric Oxygen Therapy (HBOT) when toxicity is grade ≥2.

Background

Radiation is frequently used for prostate cancer, but a 5–20% incidence of late radiation proctitis and cystitis exists. Some clinical and dosimetric factors have been defined without a full agreement. For patients diagnosed of late chronic proctitis and/or cystitis grade ≥2 treatment is not well defined. Hyperbaric Oxygen Therapy (HBOT) has been used, but its effectiveness is not well known.

Materials and methods

257 patients were treated with radiation therapy for prostate cancer. Clinical, pharmacological and dosimetric parameters were collected. Patients having a grade ≥2 toxicity were treated with HBOT. Results of the intervention were measured by monitoring toxicity by Common Toxicity Criteria v3 (CTCv3).

Results

Late rectal toxicity was related to the volume irradiated, i.e. V50 > 53.64 (p = 0.013); V60 > 38.59% (p = 0.005); V65 > 31.09% (p = 0.002) and V70 > 22.81% (p = 0.012). We could not correlate the volume for bladder. A total of 24 (9.3%) patients experienced a grade ≥2. Only the use of dicumarinic treatment was significant for late rectal toxicity (p = 0.014). A total of 14 patients needed HBOT. Final percentage of patients with a persistent toxicity grade ≥2 was 4.5%.

Conclusion

Rectal volume irradiated and dicumarinic treatment were associated to late rectal/bladder toxicity. When toxicity grade ≥2 is diagnosed, HBOT significantly ameliorate symptoms.     

Differences in synovial fluid cytokine levels but not in synovial tissue cell infiltrate between anti-citrullinated peptide/protein antibody-positive and –negative rheumatoid arthritis patients

Introduction

Comparative data on synovial cell infiltrate and cytokine levels in anti citrullinated peptide/protein antibody (ACPA)-positive and ACPA negative rheumatoid arthritis (RA) patients are scarce. Our aim was to analyze synovial cell infiltrate and synovial fluid (SF) levels of cytokines in patients with RA according to the presence or absence of ACPA in serum.

Methods

A cross-sectional study in a single center including consecutive RA patients was performed. Patients were defined as ''ACPA negative'' if serum was negative to two different ACPAs [second generation commercial anti-cyclic citrullinated peptide antibodies (CCP2) and chimeric fibrin/filaggrin citrullinated antibodies]. Parallel synovial tissue (ST) biopsies and SF were obtained by knee arthroscopy. Synovial cell infiltrate and endothelial cells were analyzed by immunohistochemistry and SF levels of Th1, Th2, Th17 and pro-inflammatory cytokines by Quantibody(R) Human Array.

Results

A total of 83 patients underwent arthroscopy, with a mean age of 55.9 ± 12 years, and mean disease duration of 45 months (interquartile range, IQR 10.8 to 122). 62% were female and 77% were ACPA positive. No significant differences were found in clinical variables, acute phase reactants, synovial cell infiltrate or lymphoid neogenesis (LN) between ACPA positive and negative patients. However ACPA positive patients had significantly higher levels of IL-1β, IL-10, IL-17 F and CC chemokine ligand 20 (CCL-20) than ACPA negative patients.

Conclusions

In our cohort of patients with RA no significant differences were found in synovial cell infiltrate or synovial LN according to ACPA status. However, ACPA positive patients had higher levels of T-cell derived and pro-inflammatory cytokines than ACPA negative patients. As systemic and local inflammation was similar in the two groups, these findings support a distinct synovial physiopathology.     

Radio-chemotherapy in anal cancer: Institutional experience at a large radiation oncology center in Chile

Aim

In this article the aim is to provide a concise narrative review and inform the institutional experience at a referral center in Chile with the use of radio-chemotherapy in anal cancer.

Background

Cancer of the anus and anal canal is mainly a loco-regional disease. For years the standard of care has been concomitant radio-chemotherapy, which permits organ preservation and better local control than alternative surgical procedures.

Materials and methods

A retrospective analysis of 44 patients treated between 2002 and 2010 was performed. Local recurrence, distant recurrence and overall survival were analyzed with the Kaplan–Meier method. Relevant groups where compared with the log-rank test and univariate analysis were done with the Cox proportional hazards model.

Results

Median follow-up of the cohort was 56 months, with a minimum follow-up of at least 24 months. There was a significant difference between clinical stages in disease free survival (log-rank trend p < 0.001), and a significant difference in overall survival (OS) when comparing clinical stages that were grouped in stage I–IIIa and IIIB (log-rank p = 0.001). On univariate analysis, age older than 60, having received full treatment and dose above 45 Gy were all significantly related to OS (p < 0.05). An overall survival of 45% and disease free survival of 45% at 5 years were found in our series.

Conclusions

Our findings show that results at the Instituto de Radiomedicina in Chile are comparable to published literature. Dismal results in stage IIIb cases indicate much work remains in therapies to achieve loco-regional control in locally advanced cases.     

Neoadjuvant oral vs. infusional chemoradiotherapy on locally advanced rectal cancer: Prognostic factors

Aim

To evaluate the prognostic factors and impact on survival of neoadjuvant oral and infusional chemoradiotherapy in patients with locally advanced rectal cancer.

Background

There is still no definitive consensus about the prognostic factors and the impact of neoadjuvant chemoradiotherapy on survival. Some studies have pointed to an improvement in overall survival (OS) and progression-free survival (PFS) in patients with tumor downstaging (TD) and nodal downstaging (ND).

Materials and methods

A set of 159 patients with LARC were treated preoperatively. Group A – 112 patients underwent concomitant oral chemoradiotherapy: capecitabine or UFT + folinic acid. Group B – 47 patients submitted to concomitant chemoradiation with 5-FU in continuous infusion. 63.6% of patients were submitted to adjuvant chemotherapy.

Results

Group A: pathologic complete response (pCR) – 18.7%; TD – 55.1%; ND – 76%; loco-regional response – 74.8%. Group B: pCR – 11.4%; TD – 50%; ND – 55.8%; LRR – 54.5%. The loco-regional control was 95.6%. There was no difference in survival between both groups. Those with loco-regional response had better PFS.

Conclusions

Tumor and nodal downstaging, loco-regional response and a normal CEA level turned out to be important prognostic factors in locally advanced rectal cancer. Nodal downstaging and loco-regional response were higher in Group A. Those with tumor downstaging and loco-regional response from Group A had better OS. Adjuvant chemotherapy had no impact on survival except in those patients with loco-regional response who achieved a higher PFS.