Early evaluation of neoadjuvant chemotherapy response using FDG-PET/CT predicts survival prognosis in patients with head and neck squamous cell carcinoma

Background

The purpose of this study was to investigate the possibility of early survival prediction after completion of one cycle of neoadjuvant chemotherapy (NAC) by positron emission tomography (PET)/computed tomography (CT) with ¹⁸F-fluorodeoxyglucose (FDG).

Methods

Fifty-seven patients with advanced head and neck squamous cell carcinoma (HNSCC) underwent FDG-PET/CT scans twice, before and after one cycle of NAC. We calculated the maximal standardized uptake value (SUV_max) for a primary tumor and/or metastatic lymph nodes and defined %decrease as the %difference in SUV_max between the two scans divided by that of the initial scan. Patients were classified as responders by PET (%decrease ≥55.5% or post-NAC SUV_max ≤3.5) and by RECIST (≥30% decrease in size). The local control (LC) rate and the disease-specific survival (DSS) rate were assessed between the responders and non-responders. Multivariate analysis was also performed using the Cox proportional hazards model.

Results

In univariate analysis, the PET finding of a primary site was a significant risk factor for LC and DSS rates at 2 years after completion of NAC (P = 0.03 and 0.02, respectively), but there was no difference between responders and non-responders by the RECIST criteria. In a multivariate regression analysis, the PET finding in the primary site and the definitive therapy choice were independent prognostic factors in LC, while the PET finding in the primary site was the only independent prognostic factor in DSS.

Conclusion

Our preliminary data indicate that the PET finding in the primary lesion after one cycle of NAC was an independent prognostic factor in LC and DSS in patients with HNSCC.     

Accuracy and axilla sparing potentials of sentinel lymph node biopsy with methylene blue alone performed before versus after neoadjuvant chemotherapy in breast cancer: a single institution experience

Introduction

The timing of sentinel lymph node biopsy (SLNB) of breast cancer in the neoadjuvant setting is still controversial. We retrospectively analyzed a Chinese patient cohort with neoadjuvant chemotherapy (NAC) to evaluate the accuracy and axilla sparing potentials of different SLNB timings with methylene blue alone for lymphatic mapping.

Materials and methods

Patients with NAC and axillary lymph node dissection (ALND) and either pre- or post-NAC SLNB were eligible. Clinicopathological characteristics, identification rate (IR), false-negative rate (FNR), accuracy, and positive-predictive value were calculated and compared between the pre- and post-NAC SLNB group using appropriate statistical methods. Axilla sparing potentials of different SLNB timings were evaluated and compared.

Results

One hundred and fifteen eligible cases were included, and 58 had pre-NAC SLNB while the other 57 had post-NAC SLNB. Both groups were comparable in clinicopathological characteristics, neoadjuvant treatments and pathologic complete response rate. IR, FNR, and accuracy of SLNB, as pre-NAC versus post-NAC, were 100 versus 98.2 % (P = 0.496), 0 versus 8.0 % (P = 0.181), and 100 versus 96.4 % (P = 0.239), respectively. Post-NAC SLNB had significantly higher positive-predictive value for ALNs than pre-NAC SLNB (70.0 vs. 36.4 %, P = 0.014), suggesting as high as 63.6 % of ALND performed in the pre-NAC group could have been avoided while only 30 % of ALND in the post-NAC group were theoretically unnecessary.

Conclusions

Both SLNB timings of breast cancer patients with NAC were feasible and accurate. Although pre-NAC SLNB tends to be better in accuracy, post-NAC SLNB is significantly superior in terms of axilla sparing.     

Gastric cancers with microsatellite instability exhibit high fluorodeoxyglucose uptake on positron emission tomography

Background

Gastric cancers exhibit various degrees of ¹⁸F-fluorodeoxyglucose (FDG) uptakes on positron emission tomography/computed tomography (PET/CT) imaging. The aim of this study was to evaluate whether FDG uptake in gastric cancer varies according to the microsatellite instability (MSI) status.

Methods

Consecutive gastric cancer patients who underwent PET/CT imaging and MSI analysis were included in the study. The maximum standardized uptake value (SUV_max) of gastric cancer was assessed using PET/CT imaging.

Results

Of 131 gastric cancers, 16 exhibited a high incidence of MSI (MSI-H) and 3 exhibited a low incidence of MSI (MSI-L). In 29 subjects who showed no uptake on PET/CT imaging the gastric cancers were all microsatellite stable (MSS). Gastric cancers with MSI were related to age older than 60 years (p = 0.002), cancer volume larger than 10 cm³ (p = 0.015), and the presence of FDG uptake on PET/CT imaging (p = 0.001). A higher SUV_max of gastric cancer was linked to the presence of MSI (p < 0.001).

Conclusion

The presence of MSI is related to FDG uptake in gastric cancer. Care should be taken with MSS gastric cancers, because they show lower SUV_max on PET/CT imaging than MSI gastric cancers.     

Response to chemotherapy estimates by FDG PET is an important prognostic factor in patients with Ewing sarcoma

Background

Response to chemotherapy is a prognostic factor in patients with Ewing sarcoma (ES); the role of FDG PET to predict response in these patients has not been thoroughly investigated. We evaluated the diagnostic accuracy and the potential of FDG PET to predict response to chemotherapy (CHT).

Materials and methods

We analyzed data of 50 patients with ES (median age 12.6 years). All patients were treated with neoadjuvant CHT, and underwent surgery for local control. All patients had ¹⁸F-FDG PET/CT at diagnosis and after induction CHT, prior to local control. We compared response assessed by histopathology with FDG PET using standard uptake values (SUVs).

Results

Median SUV at diagnosis (SUV I) was 5 (range 1.2–17), and median SUV after neoadjuvant chemotherapy (SUV II) was 1.8 (range 0–8.4). Median SUV II/I ratio was 0.3 (range 0–1). SUV at diagnosis was significantly lower in patients with good histological response than in patients with poor histological response (median 3.8 vs. 7.2, p 0.02). We found a significant correlation between SUV II and outcome; the positive predictive value of an SUV II ≤ 2.5 for favorable response was 84.21 %, and the median SUV II was significantly higher in patients with disease progression (2.3 vs. 1.6, p = 0.04). In multivariate analysis, necrosis and SUV II were significant predictors of outcome.

Conclusions

¹⁸F-FDG PET demonstrates high diagnostic accuracy for response to initial chemotherapy in patients with ES and it correlates with outcome. The role of FDG PET in predicting response and outcome should be further investigated.

     

Impact of biomarker changes during neoadjuvant chemotherapy for clinical response in patients with residual breast cancers

Background

Residual cancer burden or Ki67 expression levels in residual tumors reportedly provided significant prognostic information for a non-pathological complete response subset after neoadjuvant chemotherapy (NAC). However, the significance of Ki67 reduction for clinical response during chemotherapy in each subtype or menopausal status is yet to be determined.

Methods

A total of 183 breast cancers surgically removed after chemotherapy were recruited for this study. Expression levels of estrogen receptor (ER), progesterone receptor (PgR), and Ki67 were determined immunohistochemically for semiquantitative measurement and these biomarkers were compared in pre- and post-NAC samples from pathological non-responders (n = 125). Responses to chemotherapy were evaluated both clinically and pathologically.

Results

Ki67 expression levels after NAC (median 5 %, range 0–70 %) were significantly reduced compared with before NAC (25, 1–80 %, P < 0.0001), but only in patients who attained clinical response. This significant suppression of Ki67 in clinical responders was consistently observed in breast cancers from the ER-positive subset, but not the ER-negative subset in the total test set (n = 120). These observations were also made in the validation set (n = 63). Among premenopausal, but not postmenopausal patients, a significant decrease in PgR expression levels was detected in breast cancers of patients who attained clinical response (pre-NAC 50, 0–100 %, post-NAC 5, 0–20 %; P = 0.0003).

Conclusion

The impact of Ki67 suppression on clinical response seems to be restricted to ER-positive breast cancers. Since PgR expression levels of premenopausal ER-positive cancers were significantly reduced in clinical responders, inhibition of estrogen signaling due to chemotherapy-induced amenorrhea may be involved in this association.

     

Role of 18F-PET/CT in Predicting Prognosis of Patients With Breast Cancer After Neoadjuvant Chemotherapy

Background

Breast cancer can be assessed preoperatively and postoperatively using ¹⁸F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT). We prospectively analyzed the maximum baseline standardized uptake value (SUVmax) derived from FDG PET/CT to predict the outcomes after neoadjuvant chemotherapy (NAC) for breast cancer.

Sentinel lymph node biopsy after neoadjuvant chemotherapy predicts pathological axillary lymph node status in breast cancer patients with clinically positive axillary lymph nodes at presentation

Background

It is still controversial whether axillary lymph node (ALN) dissection (ALND) can be omitted after negative sentinel lymph node (SLN) biopsy (SLNB) in breast cancer (BC) patients with clinically positive ALNs at presentation treated with neoadjuvant chemotherapy (NAC). The study aim was to analyze whether SLNB could be useful in these patients.

Methods

In a retrospective study, eligible patients were women with invasive BC with clinically positive ALNs at presentation, treated with NAC then a total or partial mastectomy, with an intraoperative histological examination of SLNs and non-SLNs suspicious for metastasis followed by ALND. Non-SLNs suspicious for metastasis were defined as hard or large nodes located in the same level of the axilla where clinically positive ALNs had been initially identified. The results of SLNB and clinicopathological characteristics were analyzed for correlation with pathological ALN status.

Results

In a consecutive series of 105 women with 107 BC cases, 81 (75.7 %) had at least 1 SLN, and the remaining 26 (24.3 %) had at least 1 non-SLN suspicious for metastasis. The intraoperative (or final) histological examination of these nodes revealed that the false-negative (FN) rate and accuracy were 8.2 (or 6.3) % and 95.1 (or 96.3) %, respectively. Estrogen receptor status at presentation, pathological tumor response, lymphovascular invasion after NAC, and NAC regimen were correlated with pathological ALN status.

Conclusion

The histological examination of SLNs and that of non-SLNs suspicious for metastasis are useful for predicting pathological ALN status in BC patients with clinically positive ALNs at presentation who are treated with NAC.     

Integration of radiotherapy and chemotherapy for abdominal lymph node recurrence in gastric cancer

Purpose

Abdominal lymph node (ALN) recurrence in gastric cancer (GC) is rare and usually unresectable. We investigated the effects of integration of radiotherapy (RT) and chemotherapy against ALN recurrence in GC.

Methods

We retrospectively categorized GC patients with ALN recurrence treated between 2005 and 2013 into two groups: those treated with integration of RT and chemotherapy (RCT) and those who received systemic chemotherapy only (CT). The median follow-up period after ALN recurrence for all patients was 20 months.

Results

Of 53 patients, 31 and 22 were in the RCT and CT groups, respectively. Isolated distant failure (DF; 35.5%) without local progression (LP) was the dominant pattern of failure (POF) in the RCT group (median DF-free period, 26 months). LP followed by DF (31.8%) was the dominant POF in the CT group; LP (median LP-free period, 8 months) occurred 10 months earlier than DF (median DF-free period, 18 months). RCT patients had significantly longer median progression-free survival (PFS) compared to CT patients (25 vs. 8 months; P = 0.021). On multivariate analysis, treatment (CT vs. RCT) was an independent prognostic factor for PFS (hazard ratio 2.085; 95% confidence interval 1.073–4.050; P = 0.013).

Conclusions

Integration of RT and chemotherapy achieved long-term local control and prolonged PFS in GC patients with ALN recurrence. Local RT is feasible for treating isolated ALN recurrences.

     

Comparison of tumor-infiltrating lymphocytes of breast cancer in core needle biopsies and resected specimens: a retrospective analysis

Purpose

Few studies evaluated the prognostic value of the presence of lymphovascular invasion (LVI) after neoadjuvant chemotherapy (NAC) for breast cancer (BC).

Methods

The association between LVI and survival was evaluated in a cohort of BC patients treated by NAC between 2002 and 2011. Five post-NAC prognostic scores (ypAJCC, RCB, CPS, CPS + EG and Neo-Bioscore) were evaluated and compared with or without the addition of LVI.

Results

Out of 1033 tumors, LVI was present on surgical specimens in 29.2% and absent in 70.8% of the cases. Post-NAC LVI was associated with impaired disease-free survival (DFS) (HR 2.54; 95% CI 1.96–3.31; P < 0.001), and the magnitude of this effect depended on BC subtype (P_interaction = 0.003), (luminal BC: HR 1.83; P = 0.003; triple negative BC: HR 3.73; P < 0.001; HER2-positive BC: HR 6.21; P < 0.001). Post-NAC LVI was an independent predictor of local relapse, distant metastasis, and overall survival; and increased the accuracy of all five post-NAC prognostic scoring systems.

Conclusions

Post-NAC LVI is a strong independent prognostic factor that: (i) should be systematically reported in pathology reports; (ii) should be used as stratification factor after NAC to propose inclusion in second-line trials or adjuvant treatment; (iii) should be included in post-NAC scoring systems.

     

Clinicopathological correlation for the role of fluorodeoxyglucose positron emission tomography computed tomography in detection of choroidal malignant melanoma

Background

The purpose of this study was to redefine the role of whole-body 2-[¹⁸F]fluoro-2-deoxy-d-glucose (FDG) positron emission tomography fused with computed tomography (PET/CT) in the clinical diagnosis of choroidal malignant melanoma.

Methods

The study design was a retrospective case series involving 7 consecutive patients with choroidal malignant melanoma who underwent enucleation to reach the final pathological diagnosis. FDG-PET/CT was performed together with magnetic resonance imaging and ophthalmological examinations before the surgery. The area, thickness, longest diameter, and circumference of the tumor mass were measured on pathological sections, and were correlated with maximum standardized uptake values (SUVmax) of the tumors on FDG-PET/CT.

Results

Abnormally high uptake of FDG was noted in the affected eyes of 5 patients, but not in the eyes of 2 patients. The 5 patients with high uptake showed nodular tumors extruding into the vitreous cavity while the 2 patients with absence of uptake showed diffusely infiltrating tumors in the wide area of the choroid with or without a small mushroom-like protrusion. One patient with diffuse infiltration showed concurrent liver metastases with high uptake on PET/CT while another patient with a nodular tumor developed liver metastases a year later. The tumors with higher SUVmax had a tendency to have a wider area and greater thickness on pathological sections (ρ = 0.775, P = 0.0557, Spearman rank correlation test).

Conclusions

FDG-PET/CT showed correlation of the uptake with tumor sizes but was limited in detecting diffusely infiltrating tumors in the choroid without nodular formation.     

Predictive and prognostic value of early response assessment using 18FDG-PET in advanced non-small cell lung cancer patients treated with erlotinib

Background

[18F]fluorodeoxyglucose (FDG)-PET is being evaluated as a tool for the early detection of response to various targeted agents in solid tumors. The aim of this study was to evaluate the predictive value of PET response after 2 days of erlotinib in unselected pretrated patients with stage IV NSCLC.

Patients and methods

FDG-PET/CT scans were conducted at baseline and after 2 days of erlotinib, with a CT evaluation performed at baseline and after 45–60 days of therapy. PET responses were evaluated by quantitative changes on SUVmax tumor/non-tumor ratio and classified according to EORTC criteria. PET responses were compared with RECIST responses and related to progression-free (PFS) and overall (OS) survival. Erlotinib effects on glucose uptake were also studied in a panel of NSCLC cell lines.

Results

Fifty-three patients were enrolled. At 2 days of erlotinib, 20 (38 %) patients showed partial metabolic response (PMR), 25 (47 %) had stable metabolic disease (SMD) and 8 (15 %) had progressive metabolic disease (PMD). All patients with PMD had confirmed RECIST progression at 45–60 days. Patients with early PMR and SMD had significantly longer PFS (p < 0.001 and p = 0.001, respectively) and OS (p = 0.001 for both) than PMD patients.

Conclusions

FDG-PET assessment after 2 days of erlotinib could be useful to identify early resistent patients and to predict survival in unselected NSCLC pretreated population.     

Diagnostic performance of fluorodeoxyglucose-positron emission tomography/computed tomography combined with ultrasonography-guided fine needle aspiration cytology for identifying axillary lymph node status in patients with breast cancer

Aim

The aim of this study was to assess the diagnostic performance of fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) in combination with ultrasonography-guided fine needle aspiration cytology (US-guided FNAC) for the preoperative diagnosis of axillary lymph node (ALN) metastases in patients with breast cancer.

Materials and methods

A total of 318 patients with breast cancer were recruited retrospectively. Some of the cases that underwent neoadjuvant chemotherapy (NAC) were included. The sensitivity and specificity of FDG-PET/CT were calculated. We assessed the relationship between the combined results for US-guided FNAC with FDG-PET/CT and the pathological ALN status.

Results

A total of 271 patients underwent FDG-PET/CT. Of these patients, 41 underwent US-guided FNAC. The sensitivity and the specificity of FDG-PET/CT for the cases without NAC were 18.5%, 97.1%, respectively. The sensitivity in cases with NAC was 68.2%. As a whole, the sensitivity was 40.8%.ALN metastasis was detected using US-guided FNAC in a case with a negative FDG uptake in the ALN. The T stage was T2 in the case and the FDG uptake at the primary site was poor.

Conclusion

FDG-PET/CT has a good specificity for ALN metastasis, although its sensitivity is limited, especially in early-stage cases. In cases with a negative FDG uptake in the ALN, US-guided FNAC may play a role in the detection of lymph node metastasis when the primary tumor size is large and the FDG uptake in the primary tumor is low.     

Axillary Lymph Node-to-Primary Tumor Standard Uptake Value Ratio on Preoperative 18F-FDG PET/CT: A Prognostic Factor for Invasive Ductal Breast Cancer

Purpose

This study assessed the axillary lymph node (ALN)-to-primary tumor maximum standard uptake value (SUV_max) ratio (ALN/T SUV ratio) in invasive ductal breast cancer (IDC) on preoperative ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) to determine the effectiveness in predicting recurrence-free survival (RFS).

Methods

One hundred nineteen IDC patients (mean age, 50.5±10.5 years) with pathologically proven ALN involvement without distant metastasis and preoperative FDG PET/CT were enrolled in the study. SUV_max values of the ALN and primary tumor were obtained on FDG PET/CT, and ALN/T SUV ratio was calculated. Several factors were evaluated for their effectiveness in predicting RFS. These included several parameters on FDG PET/CT as well as several clinicopathological parameters: pathologic tumor/node stage; nuclear and histological grade; hormonal state; status with respect to human epidermal growth factor receptor 2, mindbomb E3 ubiquitin protein ligase 1 (MIB-1), and p53; primary tumor size; and ALN size.

Results

Among 119 patients with breast cancer, 17 patients (14.3%) experienced relapse during follow-up (mean follow-up, 28.4 months). The ALN/T SUV ratio of the group with disease recurrence was higher than that of the group without recurrence (0.97±1.60 and 0.45±0.40, respectively, p=0.005). Univariate analysis showed that the primary tumor SUV_max, ALN SUV_max, ALN/T SUV ratio, ALN status, nuclear and histological grade, estrogen receptor (ER) status, and MIB-1 status were predictors for RFS. Among these variables, ALN/T SUV ratio with hazard ratio of 4.20 (95% confidence interval [CI], 1.74-10.13) and ER status with hazard ratio of 4.33 (95% CI, 1.06-17.71) were predictors for RFS according to multivariate analysis (p=0.002 and p=0.042, respectively).

Conclusion

Our study demonstrated that ALN/T SUV ratio together with ER status was an independent factor for predicting relapse in IDC with metastatic ALN. ALN/T SUV ratio on preoperative FDG PET/CT may be a useful marker for selecting IDC patients that need adjunct treatment to prevent recurrence.     

Diffusion-weighted imaging reflects pathological therapeutic response and relapse in breast cancer

Background

Conventional imaging does not always accurately depict the pathological response to neoadjuvant chemotherapy (NAC). Diffusion-weighted imaging (DWI) may provide additional insight into the chemotherapeutic effect. This study assessed whether the apparent diffusion coefficient (ADC) correlated with pathological outcome and prognosis in breast cancer patients receiving NAC.

Methods

Fifty-six patients with locally advanced breast cancer received surgery after NAC. Dynamic contrast-enhanced (DCE) and DWI were performed before and after NAC. The pathological response was classified into five categories from no response to complete response according to amount of residual cancer. The correlation between ADC and postoperative pathologic and prognostic outcome was assessed.

Results

The distribution of the pathological response classification was as follows: no response, 3 cases; mild response, 22 cases; moderate response, 12 cases; marked response, 11 cases; complete response, 8 cases. ADC after NAC correlated with pathological response, but ADC before NAC did not. The change in ADC after chemotherapy had better correlation coefficient (r = 0.67) than change in size (r = 0.58) and ADC after NAC (r = 0.64). Although the group with larger change of tumor size showed only marginal significance compared with the smaller change group (p = 0.089), the group with higher change of ADC showed significantly better prognosis than the lower one (p = 0.038).

Conclusions

Change in ADC after chemotherapy better correlated with pathological outcome and prognosis than change in tumor size. DWI has potential in evaluating the pathological outcome of NAC in breast cancer patients.     

A phase I pharmacodynamic trial of sequential sunitinib with bevacizumab in patients with renal cell carcinoma and other advanced solid malignancies

Background

Sunitinib treatment results in a compensatory increase in plasma VEGF levels. Acute withdrawal of sunitinib results in a proliferative withdrawal flare, primarily due to elevated VEGF levels. Concurrent sunitinib plus bevacizumab is poorly tolerated with high (37 %) incidence of microangiopathic hemolytic anemia (MAHA). We evaluated a sequential design administering bevacizumab during the sunitinib treatment break to suppress the sunitinib withdrawal flare.

Methods

Patients with no prior VEGF treatment were enrolled in this study. All patients had target lesions amenable to serial FLT PET/CT imaging. Sunitinib 37.5 mg was given on days 1–28 every 6 weeks with bevacizumab 5 mg/kg on day 29. If safe and tolerable, sunitinib increased to 50 mg. FLT PET/CT scans would be obtained at baseline (D1), week 4, and week 6 to evaluate pharmacodynamics of the sequential combination. Sunitinib pharmacokinetics and total, free, and bound VEGF levels were obtained on each cycle at D1, pre-bevacizumab (D29), 4 h post-bevacizumab (D29H4), and day 42 (D42).

Results

Six patients enrolled in the safety cohort of sunitinib 37.5 mg plus bevacizumab (see Table). One patient experienced grade 1 MAHA, and after discussion with the Cancer Therapy Evaluation Program (CTEP), the trial was closed to further accrual. No imaging scans were obtained due to early closure.

The prognostic value of volume-based parameters using <Superscript>18</Superscript>F-FDG PET/CT in gastric cancer according to HER2 status

Background

We aimed to find the clinical value of metastatic tumor burden evaluated with F18-FDG PET/CT in gastric cancer patients, considering the human epidermal growth factor receptor 2 (HER2) status.

Methods

We retrospectively reviewed 124 patients with locally advanced or metastatic gastric cancer at Yonsei Cancer Center between January 2006 and December 2014 who had undergone baseline FDG PET/CT before first-line chemotherapy. We measured the maximum standardized uptake value from the primary tumor (SUV_max) and whole-body (WB) PET/CT parameters, including WB SUV_max, WB SUV_mean, WB metabolic tumor volume (WB MTV), and WB total lesion glycolysis (WB TLG), in all metabolically active metastatic lesions (SUV threshold ≥2.5 or 40% isocontour for ≤2.5), and we determined their association with patient survival outcomes.

Results

SUV_max was higher in HER2-positive gastric cancers (median 12.1, range 3.4–34.6) compared to HER-2 negative (7.4, 1.6–39.1, P < 0.001). Among all patients, WB TLG > 600, which is indicative of a high metastatic tumor burden, showed worse progression-free survival (PFS) [hazard ratio (HR), 2.003; 95% CI, 1.300–3.086; P = 0.002] and overall survival (OS) (HR, 3.001; 95% CI, 1.950–4.618; P < 0.001) than did WB TLG ≤ 600. Among HER2-positive gastric cancer patients treated with trastuzumab, higher metabolic tumor burden predicted worse OS, but not PFS.

Conclusions

HER2-positive gastric cancers had higher SUV_max compared to HER2-negative gastric cancers. In both HER2-negative patients and -positive patients receiving trastuzumab, FDG PET/CT volume-based parameters may have a role in further stratifying the prognosis of stage IV gastric cancer.

     

A phase I and pharmacokinetic study of capecitabine in combination with radiotherapy in patients with localised inoperable pancreatic cancer

Background

Antibodies targeting epidermal growth factor receptor (EGFR), such as cetuximab, may potentially improve outcome in non-small cell lung cancer (NSCLC) patients with high EGFR expression. The EGFR expression may be heterogeneously distributed within tumors, and small biopsies may thus not accurately reveal the EGFR expression. In addition, EGFR expression may also change during chemotherapy. The current study investigates the magnitude of these two issues.

Materials and methods

EGFR expression in diagnostic biopsies and resection specimen was compared in 53 NSCLC patients stage T1-4N0-1M0 treated with surgery without preceding chemotherapy (OP group), and 65 NSCLC patients stage T1-3N0-2M0 (NAC group) treated with preoperative carboplatin and paclitaxel in order to evaluate the discordance of EGFR expression between samples.

Results

Discordance between tumors dichotomized according to EGFR expression (high: H-score ≥200; low: H-score <200) in diagnostic biopsies and immediate resection specimens was 25 % in the OP group and 33 % in the NAC group (p = 0.628). Five (9 %) of primary tumors in the OP group and 4 (13 %) in the NAC group had increased EGFR expression in the resection specimens as compared to the diagnostic biopsies (p = 0.583). A decrease in EGFR expression was observed in 6 (11 %) in the OP group and 7 (23 %) in the NAC group (p = 0.148).

Conclusion

EGFR expression in 25 % of diagnostic biopsies may potentially not be accurate compared to the prevailing pattern in the whole tumor based on the larger resection specimens. This may potentially be an obstacle for proper use of antibodies targeting the EGFR in NSCLC. EGFR expression does, however, not change significantly during paclitaxel and carboplatin and rebiopsies in order to decide on anti-EGFR antibody therapy following chemotherapy do not seem warranted.     

Clinical outcomes of IMRT planned with or without PET/CT simulation for patients with pharyngeal cancers

Background

Clinical results of computed tomography (CT) simulations and [¹⁸F]-fluoro-2-deoxyglucose (FDG) positron emission tomography (PET)/CT simulations were compared retrospectively.

Materials and methods

Between 2006 and 2011, [¹⁸F]-FDG PET/CT simulation was performed on 68 consecutive patients with pharyngeal cancers (PET/CT group). As an historical control, conventional CT simulation was performed on 56 consecutive patients with pharyngeal cancer between 2000 and 2006 (CT group). In the PET/CT group, the primary sites were nasopharynx (NPC), oropharynx (OPC), and hypopharynx (HPC) in 35, 20, and 13 patients, respectively; in the CT group, the primary sites were NPC, OPC, and HPC in 21, 17, and 18 patients, respectively. All but five patients in the PET/CT group were treated with intensity modulated radiation therapy (IMRT).

Results

In the PET/CT group, TNM and clinical stages changed in 11 (16 %) and eight (12 %) patients, respectively. Although the 5-year overall survival (OS) rates for the PET/CT and the CT groups were 80 and 64 %, respectively (p = 0.0420), this result may be attributable to the background difference between the two groups. Similarly, the 5-year locoregional control rates of the two groups were 82 and 70 %, respectively (p = 0.0501). Notably, marginal recurrences around the planning target volume (PTV) were only noted in four CT group patients.

Conclusion

PET/CT simulation was useful for delineating an accurate clinical target volume (CTV) of pharyngeal cancer, and its clinical results were satisfactory.

     

Radiation therapy versus surgery for patients with cervical squamous cell carcinoma who have undergone neoadjuvant chemotherapy revisited

Background

The therapeutic significance of neoadjuvant chemotherapy (NAC) followed by radiation therapy (RT) was negated during the early 1990s. Here, we compared post-NAC RT to surgery for chemo-sensitive cervical squamous cell carcinoma (SCC).

Methods

This study included 79 consecutive patients with cervical SCC who were treated by NAC followed by surgery (n = 49) or by definitive RT (n = 30). We compared characteristics and survival outcomes between the surgery and RT groups by their responses to NAC.

Results

Of the 79 patients, 70 (89%) had stage II–IV disease and 41 (52%) had radiological pelvic lymph node enlargement. The 5-year disease-specific survival (DSS) rate of the entire cohort was 66.4% (median follow-up 54 months). Fifty-five patients (70%) achieved sufficient (complete or partial) responses to NAC. Among patients with insufficient NAC responses, the 5-year DSS rate of the surgery group (55.6%) was significantly higher than the RT group (20.0%; P = 0.044). However, among patients with sufficient responses to NAC, 5-year DSS rates did not significantly differ between the surgery and RT groups (82.3 vs 78.6%; P = 0.79) even though the RT group had many more unfavorable prognostic factors and received fewer subsequent treatments than the surgery group.

Conclusions

Post-NAC survival outcomes among patients with chemo-sensitive cervical SCC who then underwent RT were not inferior to those treated with surgery, and NAC did not detract from the efficacy of subsequent RT. Among selected patients who respond favorably to NAC, RT could be a less invasive substitute for surgery without compromising treatment outcomes.