Outcome after neoadjuvant chemoradiation and correlation with nutritional status in patients with locally advanced pancreatic cancer

Background

Cancer patients commonly suffer from weight loss since rapid tumor growth can cause catabolic metabolism and depletion of energy stores such as abdominal fat. In locally advanced pancreatic cancer this is even more pronounced due to abdominal pain, fatigue, nausea or malnutrition. In the present article, we quantify this frequently observed weight loss and assess its impact on outcome and survival.

Methods

Data on demographics, biometrics, toxicity and survival were collected for the last 100 patients treated with neoadjuvant chemoradiation for locally advanced pancreatic cancer at our department (45.0 Gy and boost up to 54.0 Gy plus concurrent and subsequent gemcitabine), and the subcutaneous fat area at the umbilicus level was measured by computer tomography before and after chemoradiation.

Results

After chemoradiation, patients showed a highly statistically significant weight loss and reduction of the subcutaneous fat area. We could determine a very strong correlation of subcutaneous fat area to patient BMI. By categorizing patients according to their BMI based on the WHO classification as slender, normal, overweight and obese, we found improved but not statistically significant survival among obese patients. Accordingly, patients who showed less weight loss tended to survive longer.

Conclusions

In this study, patients with pancreatic cancer lost weight during chemoradiation and their subcutaneous fat diminished. Changes in subcutaneous fat area were highly correlated with patients’ BMI. Moreover, obese patients and patients who lost less weight had an improved outcome after treatment. Although the extent of weight loss was not significantly correlated with survival, the observed trend warrants greater attention to nutritional status in the future.     

放化同步治疗局部进展期胰腺癌

目的评价放化综合治疗局部进展期胰腺癌（LAPC）的疗效.方法36例局部进展期胰腺癌采用放化同步治疗,化疗的方案分为：①5-Fu 500 mg,2次/周（13例）;②5-Fu 500 mg＋DDP30mg,1次/周（16例）;③健择（GEM）600mg,1次/周（7例）;所有病人均完成3～7周的化疗.20例采用常规放射治疗,中位照射剂量50 Gy（21～60 Gy）,16例采用三维适形放疗（3D-CRT）多野（3～5野）照射或补量,中位照射剂量60 Gy（50～70 Gy）.结果临床受益反应（CBR）：15例,占41.6%;全部患者近期疗效：CR 0,PR 4例占11.1%,SD 24例占66.6%,PD 8例占22.2%,其中3D-CRT的有效率（16.6%）高于常规放疗（5%,P=0.017）;全部病人生存率为：1年33.1%、2年11.2%.中位生存时间9.6个月（3～26个月）;1年生存率3D-CRT和常规放疗分别是41.2%和27.7%（P=0.41）;1～2度骨髓抑制41.6%（15例）,3度骨髓抑制8.3%（3例）,急性放射性胃肠炎1～2度52.8%（19例）,3度2.8%（1例）.结论对局部进展期胰腺癌采用放化综合治疗可取得一定的疗效,且毒副作用可耐受.     

The role of radiotherapy in locally advanced pancreatic cancer

At diagnosis, about 15% of patients with pancreatic cancer present with a resectable tumour, 50% have a metastatic tumour, and 35% a locally advanced tumour, non-metastatic but unresectable due to vascular invasion, or borderline resectable. Despite the technical progress made in the field of radiation therapy and the improvement of the efficacy of chemotherapy, the prognosis of these patients remains very poor. Recently, the role of radiation therapy in the management of pancreatic cancer has been much debated. This review aims to evaluate the role of radiation therapy for patients with locally advanced tumours.     

MRI evaluation of neoadjuvant low-dose fractionated radiotherapy with concurrent chemotherapy in patients with locally advanced breast cancer

Objectives

We address the diagnostic performance of breast MRI and the efficacy of neoadjuvant radiochemotherapy (NRC) treatment (NRC protocol) vs conventional neoadjuvant chemotherapy (NAC) in patients with locally advanced breast cancer.

Methods

The NRC protocol consists of six anthracycline/taxane cycles and concomitant low-dose radiotherapy on breast tumour volume. Breast MRI was performed at baseline and after the last therapy cycle in 18 and 36 patients undergoing the NRC protocol or conventional NAC (propensity matching).

Results

In both groups, we observed reduced tumour dimensions after the last cycle (p<0.001), and the response evaluation criteria in solid tumours (RECIST) class directly correlated with the tumour regression grade class after the last cycle (p<0.001). Patients in the NRC group displayed a higher frequency of complete/partial response than those in the NAC group (p=0.034). 17 out of 18 patients in the NRC group met the criteria for avoiding mastectomy based on final MRI evaluation. The RECIST classification displayed a superior diagnostic performance in the prediction of the response to treatment [area under the receiver operating characteristic curve (AUC)=0.72] than time-to-intensity curves and apparent diffusion coefficient (AUC 0.63 and 0.61). The association of the three above criteria yielded a better diagnostic performance, both in the general population (AUC=0.79) and in the NRC and the NAC group separately (AUC=0.82 and AUC=0.76).

Conclusions

The pathological response is predicted by MRI performed after the last cycle, if both conventional MRI and diffusion imaging are integrated. The NRC treatment yields oncological results superior to NAC.

Advances in knowledge

MRI could be used to establish the neoadjuvant protocol in breast cancer patients.Neoadjuvant chemotherapy is currently widely employed in patients with locally advanced breast cancer (LABC) in order to improve the rate of breast-conserving surgery (up to 98% of patients) and systemic control of the disease [1,2]. The coupling of pre-operative radiotherapy (RT) cycles with neoadjuvant chemotherapy has been proposed for other cancer types. In particular, taxanes could have a synergistic effect with RT when administered concurrently [3-5]. Nonetheless, few data are currently available on the efficacy of concurrent neoadjuvant RT in patients with LABC, although evidence exists that such a strategy is safe and feasible [6], and is supported by preliminary investigations [7,8]. Radiation doses below 0.5 Gy have been demonstrated to enhance the effectiveness of continuous-infusion taxanes. This phenomenon has been termed low-dose hyper-radiosensitivity [9,10].MRI is a reliable tool to evaluate the breast cancer response to chemotherapy by measuring tumour diameter changes and by assessing the viability of residual tumour areas [11-13]. Nevertheless, MRI may under- or overestimate the burden of residual tumour by confounding a fibrotic scar with viable tumour tissue, or vice versa. Diffusion-weighted imaging (DWI) has been shown in such contexts to improve the diagnostic performance of MRI [14]. It has not been clarified whether MRI retains its diagnostic performance even in the context of breast RT. The latter is known to trigger tissue oedema, which may potentially impair the diagnostic accuracy [15,16]. The purpose of the present work is to ascertain (1) the diagnostic performance of MRI and DWI-MRI in the context of concurrent low-dose fractionated RT (LD-FRT) and chemotherapy in the prediction of response to neoadjuvant treatment; (2) whether the adoption of concurrent neoadjuvant LD-FRT and chemotherapy yields better oncological results in LABC than neoadjuvant chemotherapy alone.     

Apparent diffusion coefficient for evaluating tumour response to neoadjuvant chemoradiation therapy for locally advanced rectal cancer

Objective  

To determine whether change in the apparent diffusion coefficient (ADC) before and after neoadjuvant chemoradiation therapy (CRT) for locally advanced rectal cancer (LARC) would more accurately predict pathological complete response (pCR) than analysing the pre- or post-CRT ADC individually.     

应用表观扩散系数评估局部晚期直肠癌对新辅助放化疗的反应

目的研究局部晚期直肠癌(LARC)进行新辅助放化疗前后表观扩散系数(ADC)的变化率是否比单纯测量放化疗前后的表观扩散系数能更准确地预测病理完全缓解(pCR)。方法76例局部晚期直肠癌的病人(≥T3期或淋巴结阳性)在新辅助放化疗前后进行1.5T扩散加权MRI。由1名放射医生     

Impact of intensity-modulated and image-guided radiotherapy on elderly patients undergoing chemoradiation for locally advanced head and neck cancer

Purpose

In this work, the treatment tolerance of elderly patients (≥70?years) undergoing intensity-modulated radiotherapy (IMRT) and image-guided radiotherapy (IGRT) and chemotherapy for locally advanced head and neck cancer was assessed.

Patients and methods

A retrospective review of 112?patients undergoing concurrent chemoradiation for locally advanced head and neck cancer was performed. Treatment toxicity, protocol violations, long-term complications, and survival were compared between 85?younger patients (Results Grade 3–4 treatment toxicity was observed in 88.2% and 88.8% for younger and older patients, respectively. Mean weight loss and treatment break were 5.9 and 3.9?kg (p?=?0.03) and 7.3 and 7.8?days (p?=?0.8) for younger and older patients, respectively. Seven patients (8.2%) did not complete treatment in the younger group compared to 1?patient (3.7%) in the older group (p?=?0.6). No significant differences in protocol violations and survival were found between the two groups.

Conclusion

Compared to younger patients, elderly patients with locally advanced head and neck cancer tolerated chemoradiation with IMRT and IGRT well, and should not be denied curative treatment based solely on age.     

Predicting response to neoadjuvant chemoradiation therapy in locally advanced rectal cancer: diffusion-weighted 3 Tesla MR imaging

Purpose:

To evaluate the efficacy of diffusion‐weighted imaging (DWI) on 3 Tesla (T) MR imaging to predict the tumor response to neoadjuvant chemoradiation therapy (CRT) in patients with locally advanced rectal cancer.

Materials and Methods:

Thirty‐five patients who underwent neoadjuvant CRT and subsequent surgical resection were included. Tumor volume was measured on T2‐weighted MR images before and after neoadjuvant CRT and the percentage of tumor volume reduction was calculated. The apparent diffusion coefficient (ADC) value was measured on the DWI before and after neoadjuvant CRT, and the change of ADC (Δ ADC) was calculated. The histopathologic response was categorized either as a responder to CRT or as a nonresponder. The relationship between the ADC parameters and the percentage of tumor volume reduction or histopathologic response was then evaluated.

Results:

There was a significant correlation between tumor volume reduction and pre‐CRT ADC and Δ ADC, respectively (r = ?0.352, r = 0.615). Pre‐CRT ADC of the histopathologic responders was significantly lower than that of the histopathologic nonresponders (P = 0.034). Δ ADC of the histopathologic responders was significantly higher than that of the histopathologic nonresponders (P < 0.005).

Conclusion:

DWI on 3T MR imaging may be a promising technique for helping to predict and monitor the treatment response to neoadjuvant CRT in patients with locally advanced rectal cancer. J. Magn. Reson. Imaging 2012;35:110‐116. © 2011 Wiley Periodicals, Inc.

     

Pathological correlation with diffusion restriction on diffusion-weighted imaging in patients with pathological complete response after neoadjuvant chemoradiation therapy for locally advanced rectal cancer: preliminary results

Objective The objective of this study was to assess causative pathological factors associated with diffusion restriction on diffusion-weighted imaging (DWI) in patients who achieved pathological complete response (pCR) after treatment with neoadjuvant chemoradiation therapy (CRT) for locally advanced rectal cancer. Methods In total, 43 patients with locally advanced rectal cancer (≥T3 or lymph node positive) who underwent neoadjuvant CRT, subsequent surgery and ultimately achieved pCR were enrolled. All patients underwent pre- and post-CRT 3.0 T rectal MRI with DWI. Two radiologists blinded to pathological staging reviewed pre- and post-CRT 3.0 T rectal MRI for the presence of diffusion restriction in the corresponding tumour areas on post-CRT DWI, with a third radiologist arbitrating any disagreement. The consensus of these findings was then correlated with pathological data such as intramural mucin and the degree of proctitis and mural fibrosis seen on surgical specimen. Additionally, the pre-CRT tumour volume was measured to define the effect of this variable on the degree of radiation proctitis and fibrosis, as well as the presence of intramural mucin. Results Diffusion restriction occurred in 18 subjects (41.9%), while 25 subjects remained diffusion restriction-free (58.1%). The diffusion restriction group tended to have more severe proctitis and mural fibrosis when compared with non-diffusion restriction group (p<0.001). Intramural mucin was also more common in the diffusion restriction group (p=0.052). Higher pre-CRT tumour volumes were significantly predictive of the degree of proctitis (p=0.0247) and fibrosis (p=0.0445), but not the presence of intramural mucin (p=0.0944). Proctitis and mural fibrosis severity were also identified as independent pathological risk factors for diffusion restriction on multivariate analysis (p=0.0073 and 0.0011, respectively). Conclusion Both radiation-induced proctitis and fibrosis were significant and independent predictors of diffusion restriction in patients achieving pCR after treatment with neoadjuvant CRT for locally advanced rectal cancer, and pre-CRT tumour volume significantly affects both variables.     

Systematic review of minimally invasive ablation treatment for locally advanced pancreatic cancer

Unresectable locally advanced pancreatic cancer with or without metastatic disease is associated with a very poor prognosis. Ablation techniques are based on direct application of chemical, thermal, or electrical energy to a tumor, which leads to cellular necrosis. Initial studies about ablation therapies of the pancreas were associated with significant morbidity and mortality, which limited widespread adoption. Modifications to the various applications, in particular combining the techniques with high-quality imaging and intra-operative approach has enabled real-time treatment monitoring and significant improvements in safety. Inoperable cases of pancreatic cancer have been treated by various ablation techniques in the last few years with promising results. The purpose of this review is to present the current status of local ablative therapies in the treatment of pancreatic advanced tumor.     

局部晚期宫颈癌术前新辅助化疗疗效观察

目的探讨新辅助化疗(NACT)对局部晚期宫颈癌的治疗疗效。方法选取2012年6月至2014年12月乐山市人民医院收治的74例ⅠB2~ⅡA期宫颈癌患者为研究对象。所有患者按自愿原则分为观察组(新辅助化疗+手术组)49例,对照组25例。观察组患者给予紫杉醇/多西他赛+顺铂/卡铂方案,化疗1~3个疗程后再行手术。对照组患者直接进行手术治疗。比较两组患者的手术时间、术中出血量以及术后病理情况。结果观察组患者新辅助化疗后的肿瘤消退情况,完全缓解率为14.3%,部分缓解率为61.2%,总有效率达75.5%。观察组患者的宫颈深层间质浸润、淋巴结转移、脉管癌栓、宫旁浸润、切缘阳性率均低于对照组(P<0.05);而两组患者的手术时间及术中出血量比较,差异均无统计学意义(P>0.05)。结论术前新辅助化疗对多数局部晚期宫颈癌患者具有较好的疗效,是治疗该类疾病的一种有效的辅助治疗手段。     

Simultaneous neoadjuvant radiochemotherapy with capecitabine and oxaliplatin for locally advanced rectal cancer

Background

Phase II trials of neoadjuvant treatment in UICC-TNM stage?II and III rectal cancer with capecitabine and oxaliplatin demonstrated favourable rates on tumour regression with acceptable toxicity.

Patients and methods

Retrospective evaluation of 34 patients treated from 2005–2008 outside clinical trials (CTR) with neoadjuvant irradiation (45–50.4?Gy) and simultaneous capecitabine 825?mg/m² b.i.d. on days 1–14 and 22–35 and oxaliplatin 50?mg/m² on days 1, 8, 22 and 29 (CAPOX). Twenty-six (77%) patients received one or two courses of capecitabine 1,000?mg/m² b.i.d. on days 1–14 and oxaliplatin 130?mg/m² on day 1 (XELOX) prior to simultaneous chemoradiotherapy.

Results

UICC-TNM stage regression was observed in 60% (n?=?20). Dworak’s regression grades 3 and 4 were achieved in 18.2% (n?=?6) and 15.1% (n?=?5) of the patients. Sphincter-preserving surgery was performed in 53% (n?=?8) of patients with a tumour of the lower rectum. Within the mean observation of 24 months, none of the patients relapsed locally, 1?patient had progressive disease and 5?patients (15%) relapsed distantly. Toxicity of grade 3 and 4 was mainly diarrhoea 18% (n?=?6) and perianal pain 9% (n?=?3). Nevertheless, severe cardiac events (n?=?2), severe electrolyte disturbances (n?=?2), and syncopes (n?=?2) were observed as well.

Conclusion

Treatment efficacy and common toxicity are similar to the reports of phase?I/II trials. However, several severe adverse events were observed in our cohort study. The predisposing factors for these events have yet to be studied and may have implications for the selection of patients outside CTR.     

尼妥珠单抗同步调强放射治疗对老年局部晚期子宫颈癌的安全性和有效性研究

目的 探讨尼妥珠单抗联合放疗对老年局部晚期子宫颈癌患者的安全性和有效性。方法 回顾性分析福建医科大学附属漳州市医院2020年6月至2021年12月共34例尼妥珠单抗联合调强放疗或同步放化疗治疗老年局部晚期子宫颈癌患者。评价治疗后1年和2年疗效及不良反应。结果 中位随访时间13.3个月(6.1~24.3个月)。全组完全缓解(CR)24例,部分缓解(PR)8例,客观缓解率(ORR)为94.1%(32/34)。放疗前肿瘤直径(49.56±19.22) mm,尼妥珠单抗联合外照射后,肿瘤直径(19.61±14.59) mm,肿瘤退缩率(TRR)59.22%。1、2年无进展生存率(PFS)分别为84.9%、84.9%,1、2年总生存率(OS)分别为91.8%、87.2%。1、2年无病生存率(DFS)分别为91.8%、87.2%,肿瘤特异性生存率(CSS)分别为95.7%、90.9%。主要不良事件为放射性肠炎、白细胞减少、低蛋白血症、贫血。结论 尼妥珠单抗联合放疗/同步放化疗治疗老年局部晚期子宫颈癌安全有效。     

Intensity-modulated radiotherapy for neoadjuvant treatment of gastric cancer

Radiation therapy plays an integral role in the treatment of gastric cancer in the postsurgery setting, the inoperable/palliative setting, and, as in the case of the current report, in the setting of neoadjuvant therapy prior to surgery. Typically, anterior-posterior/posterior-anterior (AP/PA) or 3-field techniques are used. In this report, we explore the use of intensity-modulated radiotherapy (IMRT) treatment in a patient whose care was transferred to our institution after 3-field radiotherapy (RT) was given to a dose of 30 Gy at an outside institution. If the 3-field plan were continued to 50 Gy, the volume of irradiated liver receiving greater than 30 Gy would have been unacceptably high. To deliver the final 20 Gy, an opposed parallel AP/PA plan and an IMRT plan were compared to the initial 3-field technique for coverage of the target volume as well as dose to the kidneys, liver, small bowel, and spinal cord. Comparison of the 3 treatment techniques to deliver the final 20 Gy revealed reduced median and maximum dose to the whole kidney with the IMRT plan. For this 20-Gy boost, the volume of irradiated liver was lower for both the IMRT plan and the AP/PA plan vs. the 3-field plan. Comparing the IMRT boost plan to the AP/PA boost-dose range (<10 Gy) in comparison to the AP/PA plan; however, the IMRT plan irradiated a smaller liver volume within the higher dose region (>10 Gy) in comparison to the AP/PA plan. The IMRT boost plan also irradiated a smaller volume of the small bowel compared to both the 3-field plan and the AP/PA plan, and also delivered lower dose to the spinal cord in comparison to the AP/PA plan. Comparison of the composite plans revealed reduced dose to the whole kidney using IMRT. The V20 for the whole kidney volume for the composite IMRT plan was 30% compared to approximately 60% for the composite AP/PA plan. Overall, the dose to the liver receiving greater than 30 Gy was lower for the composite IMRT plan and was well below acceptable limits. In conclusion, our study suggests a dosimetric benefit of IMRT over conventional planning, and suggests an important role for IMRT in the neoadjuvant treatment of gastric cancer.     

Intensity-modulated radiotherapy for neoadjuvant treatment of gastric cancer

Radiation therapy plays an integral role in the treatment of gastric cancer in the postsurgery setting, the inoperable/palliative setting, and, as in the case of the current report, in the setting of neoadjuvant therapy prior to surgery. Typically, anterior-posterior/posterior-anterior (AP/PA) or 3-field techniques are used. In this report, we explore the use of intensity-modulated radiotherapy (IMRT) treatment in a patient whose care was transferred to our institution after 3-field radiotherapy (RT) was given to a dose of 30 Gy at an outside institution. If the 3-field plan were continued to 50 Gy, the volume of irradiated liver receiving greater than 30 Gy would have been unacceptably high. To deliver the final 20 Gy, an opposed parallel AP/PA plan and an IMRT plan were compared to the initial 3-field technique for coverage of the target volume as well as dose to the kidneys, liver, small bowel, and spinal cord. Comparison of the 3 treatment techniques to deliver the final 20 Gy revealed reduced median and maximum dose to the whole kidney with the IMRT plan. For this 20-Gy boost, the volume of irradiated liver was lower for both the IMRT plan and the AP/PA plan vs. the 3-field plan. Comparing the IMRT boost plan to the AP/PA boost-dose range (<10 Gy) in comparison to the AP/PA plan; however, the IMRT plan irradiated a smaller liver volume within the higher dose region (>10 Gy) in comparison to the AP/PA plan. The IMRT boost plan also irradiated a smaller volume of the small bowel compared to both the 3-field plan and the AP/PA plan, and also delivered lower dose to the spinal cord in comparison to the AP/PA plan. Comparison of the composite plans revealed reduced dose to the whole kidney using IMRT. The V20 for the whole kidney volume for the composite IMRT plan was 30% compared to approximately 60% for the composite AP/PA plan. Overall, the dose to the liver receiving greater than 30 Gy was lower for the composite IMRT plan and was well below acceptable limits. In conclusion, our study suggests a dosimetric benefit of IMRT over conventional planning, and suggests an important role for IMRT in the neoadjuvant treatment of gastric cancer.     

Contrast enhanced ultrasound quantitative parameters for assessing neoadjuvant chemotherapy response in patients with locally advanced breast cancer

Objectives:To evaluate the role of contrast-enhanced ultrasound (CEUS) quantitative parameters in predicting neoadjuvant chemotherapy (NACT) response in patients with locally advanced breast cancer (LABC).Methods:30 patients with histologically proven LABC scheduled for NACT were recruited. CEUS was performed using a contrast bolus of 4.8 ml and time intensity curves (TICs) were obtained by contrast dynamics software. CEUS quantitative parameters assessed were peak enhancement (PE), time-to-peak (TTP), area under the curve (AUC) and mean transit time (MTT). The parameters were documented on four consecutive instances: before NACT and 3 weeks after each of the three cycles. The gold-standard was pathological response using Miller Payne Score obtained pre NACT and post-surgery.Results:A decrease in mean values of PE and an increase in mean values of TTP and MTT was observed with each cycle of NACT among responders. Post each cycle of NACT (compared with baseline pre-NACT), there was a statistically significant difference in % change of mean values of PE, TTP and MTT between good responders and poor responders (p-value < 0.05). The diagnostic accuracy of TTP post-third cycle was 87.2% (p = 0.03), and MTT post--second and third cycle was 76.7% (p = 0.004) and 86.7% (p = 0.006) respectively.Conclusion:In responders, a decrease in the tumor vascularity was reflected in the CEUS quantitative parameters as a reduction in PE, and a prolongation in TTP, MTT.Advances in knowledge:Prediction of NACT response by CEUS has the potential to serve as a diagnostic modality for modification of chemotherapy regimens during ongoing NACT among patients with LABC, thus affecting patient prognosis.     

Oxaliplatin and capecitabine concomitant with neoadjuvant radiotherapy and extended to the resting period in high risk locally advanced rectal cancer

Background

Conventional neoadjuvant chemoradiotherapy (CRT) is suboptimal for systemic control in locally advanced rectal cancer (LARC). To improve systemic control, we developed an alternative approach in which an intensified oxaliplatin and capecitabine (XELOX) chemotherapy regimen was administered concomitantly with radiation and extended to the resting period (consolidation chemotherapy) for high-risk LARC. The aim of the current study was to evaluate the short-term efficacy and toxicity of this strategy.

Methods

Patients with high-risk LARC were treated with CRT. Two cycles of XELOX were administered concomitantly with radiation. Thereafter, an additional cycle of the same regimen was administered during the resting period after completion of CRT. Tumor response, toxicities and surgical complications were recorded.

Results

This study includes 36 patients treated with the above strategy. All patients completed the planned concurrent CRT. Because of grade 3 toxicities, 2 patients were unable to complete the additional chemotherapy. Grade 3 toxicities were leucopenia (2.8?%), diarrhea (2.8?%) and radiodermatitis (2.8?%). All patients underwent optimal surgery with total mesorectal excision (TME) and a sphincter-saving procedure was performed in 27 patients (75?%). There was no perioperative mortality. Postoperative complications developed in 7 patients (19.4?%). Pathologic complete regression (pCR),“nearly pCR” (major regression), and moderate or minimal regression were achieved in 13 (36.1?%), 16 (44.4?%), and 7 patients (19.5?%), respectively.

Conclusion

The preliminary results suggest that a XELOX regimen initially administered concomitantly with radiotherapy and then extended to the resting period in high-risk LARC patients is well tolerated. The strategy is highly effective in terms of pCR and nearly pCR rates, and thus warrants further investigation.     

Changes in multimodality functional imaging parameters early during chemoradiation predict treatment response in patients with locally advanced head and neck cancer

Objective

To assess the optimal timing and predictive value of early intra-treatment changes in multimodality functional and molecular imaging (FMI) parameters as biomarkers for clinical remission in patients receiving chemoradiation for head and neck squamous cell carcinoma (HNSCC).

Methods

Thirty-five patients with stage III-IVb (AJCC 7th edition) HNSCC prospectively underwent ¹⁸F–FDG-PET/CT, and diffusion-weighted (DW), dynamic contrast-enhanced (DCE) and susceptibility-weighted MRI at baseline, week 1 and week 2 of chemoradiation. Patients with evidence of persistent or recurrent disease during follow-up were classed as non-responders. Changes in FMI parameters at week 1 and week 2 were compared between responders and non-responders with the Mann–Whitney U test. The significance threshold was set at a p value of <0.05.

Results

There were 27 responders and 8 non-responders. Responders showed a greater reduction in PET-derived tumor total lesion glycolysis (TLG_40%; p?=?0.007) and maximum standardized uptake value (SUV_max; p?=?0.034) after week 1 than non-responders but these differences were absent by week 2. In contrast, it was not until week 2 that MRI-derived parameters were able to discriminate between the two groups: larger fractional increases in primary tumor apparent diffusion coefficient (ADC; p?<?0.001), volume transfer constant (K^trans; p?=?0.012) and interstitial space volume fraction (V_e; p?=?0.047) were observed in responders versus non-responders. ADC was the most powerful predictor (? >17%, AUC 0.937).

Conclusion

Early intra-treatment changes in FDG-PET, DW and DCE MRI-derived parameters are predictive of ultimate response to chemoradiation in HNSCC. However, the optimal timing for assessment with FDG-PET parameters (week 1) differed from MRI parameters (week 2). This highlighted the importance of scanning time points for the design of FMI risk-stratified interventional studies.