Complete Primary Pathological Response Following Neoadjuvant Treatment and Radical Resection for Pancreatic Ductal Adenocarcinoma.

INTRODUCTION: Neoadjuvant treatment (NAT) for borderline (BD) or locally advanced (LA) primary pancreatic cancer (PDAC) is now a widely adopted approach. We present a case series of patients who have achieved a complete pathological response of the primary tumour on final histology following neoadjuvant chemotherapy +/- chemoradiation and radical surgery. METHODS: Patients who underwent radical pancreatic resection following neoadjuvant treatment between March 2006 and March 2023 at a single institution were identified by retrospective case note review of a prospectively maintained database. RESULTS: Ten patients were identified to have a complete primary pathological response (ypT0) on postoperative histology. Before treatment, five patients were considered BD and five were LA according to National Comprehensive Cancer Network guidelines. All patients underwent staging Computed Tomography (CT) and nine underwent 18Fluorodeoxyglucose Positron Emission Tomography (18FDG-PET/CT) imaging, with a mean maximum standardized uptake value (SUVmax) of the primary lesion at 6.14 ± 1.98 units. All patients received neoadjuvant chemotherapy, and eight received further chemoradiotherapy prior to resection. Mean pre- and post-neoadjuvant treatment serum Ca19-9 was 148.0 ± 146.3 IU/L and 18.0 ± 18.7 IU/L, respectively (p = 0.01). The mean duration of NAT was 5.6 ± 1.7 months. The mean time from completion of NAT to surgery was 13.1 ± 8.3 weeks. The mean lymph node yield was 21.1 ± 10.4 nodes, with one patient found to have 1 lymph node involved. All resections were reported to be R0. The mean length of stay was 11.8 ± 6.2 days. At the time of analysis, one death was reported at 35 months postoperatively. Two cases of recurrence were reported at 16 months (surgical bed) and 33 months (pulmonary). All other patients remain alive and under active surveillance. The current overall survival is 26.6 ± 20.7 months and counting. CONCLUSIONS: Complete primary pathological response is uncommon but possible following neoadjuvant treatment in patients with PDAC. Further work to identify the common denominator within this unique cohort may lead to advances in the therapeutic approach and offer hope for patients diagnosed with borderline or locally advanced pancreatic ductal adenocarcinoma.

Six-Month Survivorship Prediction in Spinal Metastatic Patients by Oncologists Shows Reliable Prognostication.

STUDY DESIGN: A retrospective analysis of oncologist-provided prognoses vs actual survival outcomes of patients referred with Metastatic spinal cord compression (MSCC) to a supra-regional multidisciplinary team (MDT). OBJECTIVES: Prognostic scoring systems, such as the revised Tokuhashi, are commonly used to help guide the treatment of MSCC. However, scoring systems do not accommodate for the improved outcomes of contemporary cancer therapy. Oncologist-provided prognoses play an important role in real world rapid decision making. There is a paucity of evidence assessing the accuracy of the oncologist-provided prognosis. We conducted a retrospective study to evaluate this. METHODS: Data was captured between January 2015 and December 2018. Patients were split into 2 groups: Group 1 (prognosis estimated <6 months) and Group 2 (prognosis estimated >6 months). Median overall survival (mOS) and hazard ratio for death (HR) was assessed. Receiver operating characteristic (ROC) analysis was performed to assess the accuracy of the oncologist's prognosis. RESULTS: 829 patients were included. mOS in Group 1 was 5.8 months (95% CI 4.2-7.4 m), and in Group 2 mOS was not reached. Log rank test gave a Chi2 of 131 (P < .001). Cox regression analysis revealed a HR of .30 (P < .001). Area under the ROC curve was 78%. CONCLUSIONS: Oncologist-provided prognosis is accurate in this cohort of unselected, consecutive MSCC patients. It reduced reliance on scoring systems that can become outdated. Given the rapid progress in cancer treatment, the oncologist's prognostic prediction is integral in efficient and effective MSCC management to help rapidly determine surgical candidacy.

First multicentre experience of SABR for lymph node and liver oligometastatic disease on the unity MR-Linac.

The treatment of oligometastatic disease using MR guidance is an evolving field. Since August 2018 patients are treated on a 1.5 Tesla MR-Linac (MRL). We present current workflows and practice standards from seven institutions for the initial patients treated for lymph node and liver metastases.

An international Delphi consensus for pelvic stereotactic ablative radiotherapy re-irradiation.

INTRODUCTION: Stereotactic Ablative Radiotherapy (SABR) is increasingly used to treat metastatic oligorecurrence and locoregional recurrences but limited evidence/guidance exists in the setting of pelvic re-irradiation. An international Delphi study was performed to develop statements to guide practice regarding patient selection, pre-treatment investigations, treatment planning, delivery and cumulative organs at risk (OARs) constraints. MATERIALS AND METHODS: Forty-one radiation oncologists were invited to participate in three online surveys. In Round 1, information and opinion was sought regarding participants' practice. Guidance statements were developed using this information and in Round 2 participants were asked to indicate their level of agreement with each statement. Consensus was defined as ≥75% agreement. In Round 3, any statements without consensus were re-presented unmodified, alongside a summary of comments from Round 2. RESULTS: Twenty-three radiation oncologists participated in Round 1 and, of these, 21 (91%) and 22 (96%) completed Rounds 2 and 3 respectively. Twenty-nine of 44 statements (66%) achieved consensus in Round 2. The remaining 15 statements (34%) did not achieve further consensus in Round 3. Consensus was achieved for 10 of 17 statements (59%) regarding patient selection/pre-treatment investigations; 12 of 13 statements (92%) concerning treatment planning and delivery; and 7 of 14 statements (50%) relating to OARs. Lack of agreement remained regarding the minimum time interval between irradiation courses, the number/size of pelvic lesions that can be treated and the most appropriate cumulative OAR constraints. CONCLUSIONS: This study has established consensus, where possible, in areas of patient selection, pre-treatment investigations, treatment planning and delivery for pelvic SABR re-irradiation for metastatic oligorecurrence and locoregional recurrences. Further research into this technique is required, especially regarding aspects of practice where consensus was not achieved.

A multicentre retrospective review of SABR reirradiation in rectal cancer recurrence.

BACKGROUND AND PURPOSE: Locally recurrent rectal cancer (LRRC) is associated with considerable morbidity, poor quality of life and an overall survival of 9 months. The non-operative treatment of LRRC is an understudied area, there is no consensus on management in this setting. We aim to perform a retrospective, multicentre analysis of patients treated with SABR reirradiation. MATERIALS AND METHODS: All patients were identified who received SABR re-irradiation for LRRC, at 3 UK centres, between August 2015 and September 2020. Eligible patients had pelvic recurrence and were either not suitable/opted not for surgery, or margin positive after exenturative surgery. Patients were treated with 30 Gy in 5 fractions and followed up with clinical review and CT scan at 3, 6, 12, 18 and 24 months. RESULTS: 69 patients with 81 lesions were identified and median follow up was 28 months. Median progression free survival (PFS) and overall survival (OS) were 12.1 months (10.4, 17.7) and 38.7 months (28.9,-) respectively. 2-year OS was 0.77 (0.66, 0.89). 58.3% of deaths were as a result of consequences of local relapse. 42.6% of patients had local relapse at death or last follow up. CONCLUSION: Our outcomes are encouraging for a population who had R1 resections, refused or were refused surgery; as they are similar to those in surgical series. Prospective data including details of survival, local relapse and QOL; with an optimised SABR technique, is required to establish SABR as an alternative to surgery.

Magnetic Resonance Guided Radiation Therapy for Pancreatic Adenocarcinoma, Advantages, Challenges, Current Approaches, and Future Directions.

INTRODUCTION: Pancreatic adenocarcinoma (PAC) has some of the worst treatment outcomes for any solid tumor. PAC creates substantial difficulty for effective treatment with traditional RT delivery strategies primarily secondary to its location and limited visualization using CT. Several of these challenges are uniquely addressed with MR-guided RT. We sought to summarize and place into context the currently available literature on MR-guided RT specifically for PAC. METHODS: A literature search was conducted to identify manuscript publications since September 2014 that specifically used MR-guided RT for the treatment of PAC. Clinical outcomes of these series are summarized, discussed, and placed into the context of the existing pancreatic literature. Multiple international experts were involved to optimally contextualize these publications. RESULTS: Over 300 manuscripts were reviewed. A total of 6 clinical outcomes publications were identified that have treated patients with PAC using MR guidance. Successes, challenges, and future directions for this technology are evident in these publications. MR-guided RT holds theoretical promise for the treatment of patients with PAC. As with any new technology, immediate or dramatic clinical improvements associated with its use will take time and experience. There remain no prospective trials, currently publications are limited to small retrospective experiences. The current level of evidence for MR guidance in PAC is low and requires significant expansion. Future directions and ongoing studies that are currently open and accruing are identified and reviewed. CONCLUSIONS: The potential promise of MR-guided RT for PAC is highlighted, the challenges associated with this novel therapeutic intervention are also reviewed. Outcomes are very early, and will require continued and long term follow up. MR-guided RT should not be viewed in the same fashion as a novel chemotherapeutic agent for which dosing, administration, and toxicity has been established in earlier phase studies. Instead, it should be viewed as a novel procedural intervention which must be robustly tested, refined and practiced before definitive conclusions on the potential benefits or detriments can be determined. The future of MR-guided RT for PAC is highly promising and the potential implications on PAC are substantial.

Considerations for the treatment of pancreatic cancer during the COVID-19 pandemic: the UK consensus position.

The coronavirus disease 2019 (COVID-19) pandemic epicentre has moved to the USA and Europe, where it is placing unprecedented demands on healthcare resources and staff availability. These service constraints, coupled with concerns relating to an increased incidence and severity of COVID-19 among patients with cancer, should lead to re-consideration of the risk-benefit balance for standard treatment pathways. This is of particular importance to pancreatic cancer, given that standard diagnostic modalities such as endoscopy may be restricted, and that disease biology precludes significant delays in treatment. In light of this, we sought consensus from UK clinicians with an interest in pancreatic cancer for management approaches that would minimise patient risk and accommodate for healthcare service restrictions. The outcomes are described here and include recommendations for treatment prioritisation, strategies to bridge to later surgical resection in resectable disease and factors that modify the risk-benefit balance for treatment in the resectable through to the metastatic settings. Priority is given to strategies that limit hospital visits, including through the use of hypofractionated precision radiotherapy and chemoradiotherapy treatment approaches.

Dose-Escalated Radiation Therapy for Pancreatic Cancer: A Simultaneous Integrated Boost Approach.

PURPOSE: To provide a detailed description of practical approaches to dose escalation in pancreatic cancer. METHODS AND MATERIALS: The current paper represents an international collaborative effort of radiation oncologists from the MR-linac consortium with expertise in pancreatic dose escalation. RESULTS: A 15-fraction hypofractionated intensity modulated radiation therapy (67.5 Gy in 15 fractions) and 5-fraction stereotactic body radiation therapy case (50 Gy in 5 fractions) are presented with information regarding patient selection, target volumes, organs at risk, dose constraints, and specific considerations regarding quality assurance. Additionally, we address barriers to dose escalation and briefly discuss future directions in dose escalation for pancreatic cancer, including particle therapy and magnetic resonance guided radiation therapy. CONCLUSIONS: This article on dose escalation for pancreatic cancer may help to guide academic and community based physicians and to serve as a reference for future therapeutic trials.

Comparison of the dose escalation potential for two hypofractionated radiotherapy regimens for locally advanced pancreatic cancer.

OBJECTIVES: To determine the potential for dose escalation to a biological equivalent dose BED10 ≅ 100 Gy in hypofractionated radiotherapy for locally advanced pancreatic cancer (LAPC). MATERIALS AND METHODS: Ten unselected LAPC patients were retrospectively included in the study. Two fractionation regimens were compared (5 and 15 fractions). The aim was to cover 95% of the Planning Target Volume (PTV) with a BED10 = 54 Gy (base dose = 33 Gy in 5 fractions, 42.5 Gy in 15 fractions) whilst respecting organs-at-risk (OAR) constraints. Once the highest PTV coverage was achieved dose escalation to a BED10 ≅ 100 Gy (escalated dose = 50 Gy in 5 fractions, 67.5 Gy in 15 fractions) was attempted, limiting the PTV maximum dose to 130% of the escalated dose. RESULTS: In 5 fractions, 95% PTV coverage by both base and escalated doses could be achieved for one patient with PTV more than 1 cm away from OAR. 95% and 90% PTV coverage by the base dose was achieved in one and two patients respectively. In all other patients, coverage even by the base dose had to be compromised to comply with OAR constraints. In 15 fractions, 95% PTV coverage by the base dose was feasible for all patients except one. Dose escalation allowed improvement in target coverage by the base dose in both fractionation regimen whilst covering a sub-volume of the PTV with a BED10 ≅ 100 Gy. Both fractionation schemes were equivalent in terms of dose escalation potential. CONCLUSION: LAPC patients with OAR close to the PTV are generally not eligible for hypofractionation with dose escalation. However, this planning study shows that it is possible to cover PTV sub-volumes with a BED10 ≅ 100 Gy in addition to delivering a BED10 = 54 Gy to 90-95% of the PTV as commonly prescribed to this population. Combined with an adaptive approach, this may maximize PTV coverage by a high BED on days with favourable anatomy.

Cisplatin Substitution with Carboplatin During Radical Chemoradiotherapy for Oesophagogastric Carcinoma: Outcomes from a Tertiary Centre.

BACKGROUND/AIM: Cisplatin-based radical chemoradiotherapy (CRT) is utilised in oesophagogastric (OG) cancer but the toxicity profile of cisplatin limits its use. This study aimed to evaluate the clinical characteristics and outcomes of patients treated with either cisplatin or carboplatin based CRT at our institution. MATERIALS AND METHODS: This is a retrospective analysis of patients with localised OG cancer undergoing CRT with cisplatin/fluoropyrimidine (CX/F) or carboplatin/fluoropyrimidine (CarboX/F) between January 2001 and December 2014. RESULTS: A total of 91 eligible patients were included. Median age was 65 years (IQR=57-75) for CX/F and 77 years (IQR=69-80) for CarboX/F. Adenocarcinoma histology and Charlson comorbidity index were higher in the CarboX/F group. Endoscopic complete response (CR) was achieved in 64% of CX/F group and 48% of CarboX/F group (p=0.19). The median PFS for CX/F was 31.0 months (95%CI=18.2-NE) vs. 18.7 months for CarboX/F (95%CI=13.5-30.4; HR=1.49, p=0.21). CONCLUSION: Despite significant differences in baseline clinical characteristics, patients treated with carboplatin CRT demonstrated no significant difference in PFS or endoscopic CR rate, compared to those treated with cisplatin.

Pancreatic gross tumor volume contouring on computed tomography (CT) compared with magnetic resonance imaging (MRI): Results of an international contouring conference.

PURPOSE: Accurate identification of the gross tumor volume (GTV) in pancreatic adenocarcinoma is challenging. We sought to understand differences in GTV delineation using pancreatic computed tomography (CT) compared with magnetic resonance imaging (MRI). METHODS AND MATERIALS: Twelve attending radiation oncologists were convened for an international contouring symposium. All participants had a clinical and research interest in pancreatic adenocarcinoma. CT and MRI scans from 3 pancreatic cases were used for contouring. CT and MRI GTVs were analyzed and compared. Interobserver variability was compared using Dice's similarity coefficient (DSC), Hausdorff distances, and Jaccard indices. Mann-Whitney tests were used to check for significant differences. Consensus contours on CT and MRI scans and constructed count maps were used to visualize the agreement. Agreement regarding the optimal method to determine GTV definition using MRI was reached. RESULTS: Six contour sets (3 from CT and 3 from MRI) were obtained and compared for each observer, totaling 72 contour sets. The mean volume of contours on CT was significantly larger at 57.48 mL compared with a mean of 45.76 mL on MRI, P = .011. The standard deviation obtained from the CT contours was significantly larger than the standard deviation from the MRI contours (P = .027). The mean DSC was 0.73 for the CT and 0.72 for the MRI (P = .889). The conformity index measurement was similar for CT and MRI (P = .58). Count maps were created to highlight differences in the contours from CT and MRI. CONCLUSIONS: Using MRI as a primary image set to define a pancreatic adenocarcinoma GTV resulted in smaller contours compared with CT. No differences in DSC or the conformity index were seen between MRI and CT. A stepwise method is recommended as an approach to contour a pancreatic GTV using MRI.

An evaluation of systematic errors on marker-based registration of computed tomography and magnetic resonance images of the liver.

We demonstrated a general method to evaluate systematic errors related to Magnetic Resonance (MR) imaging sequences in marker-based co-registration of MR and Computed Tomography (CT) images, and investigated the effect of MR image quality in the co-registration process using clinical MR and CT protocols for stereotactic ablative body radiotherapy (SABR) planning of the liver. Small systematic errors (under 1.6 mm) were detected, unlikely to be a clinical risk to liver SABR. The least favourable marker configuration was found to be a co-planar arrangement parallel to the transaxial image plane.

Survival Outcomes in Asymptomatic Patients With Normal Conventional Imaging but Raised Carcinoembryonic Antigen Levels in Colorectal Cancer Following Positron Emission Tomography-Computed Tomography Imaging.

BACKGROUND: This study had two aims: (a) to evaluate the utility of fluorine 18-fluorodeoxyglucose (FDG) positron emission tomography (PET)-computed tomography (CT) in detecting occult disease recurrence with raised carcinoembryonic antigen (CEA) and (b) to establish the prognostic effects of early detection of disease recurrence in patients with colorectal cancer (CRC). PATIENTS AND METHODS: Clinico-pathological data were obtained from all consecutive patients undergoing CRC surveillance from 2004 to 2010 who had an elevated CEA level (>3 ng/mL in nonsmokers, >5 ng/mL in smokers) but normal or equivocal conventional investigations. Histopathological confirmation or a minimum of 12 months' clinical and radiological follow-up were required to ascertain disease relapse. RESULTS: A total of 1,200 patients were screened; of those, 88 (59% men; mean age, 66 years [SD, 9.6]) eligible patients (67 with normal and 21 with equivocal results on conventional investigations) were identified. Recurrent disease was detected in 56 of 88 patients (64%). The sensitivity of FDG PET-CT to detect recurrence was 49 of 56 (88%; 95% confidence interval [CI], 76%-95%) and specificity was 28 of 32 (88%; 95% CI, 71%-97%). Twenty-seven of 49 (55%) patients with PET-CT-detected relapsed disease were deemed eligible for further curative therapy; 19 (70%) went on to receive potentially curative therapy. The median time to progression (8.8 months [interquartile range (IQR), 4.5-19.1 months] vs. 2.2 months [IQR, 0.7-5.6]), median overall survival (39.9 months [IQR, 23.6-65.4 months] vs. 15.6 months [IQR, 7.3-25.7 months]), and 5-year survival (36.8% [95% CI, 16.5%-57.5%] vs. 6.1% [95% CI, 1.1%-17.6%]; p ≤ .001) were higher in patients who received potentially curative therapy than in those who received noncurative therapy. CONCLUSION: FDG PET-CT is a highly sensitive and specific tool for the detection of occult CRC recurrence. In >50% of patients, recurrent disease may still be potentially amenable to curative therapy. Long-term survival can be achieved in such patients. IMPLICATIONS FOR PRACTICE: Colorectal cancer (CRC) patients who, on follow-up, have normal or equivocal results on clinical investigations but raised carcinoembryonic antigen (CEA) levels pose a significant challenge to treating physicians. This study supported the notion that the early use of fluorodeoxyglucose (FDG) positron emission tomography (PET)-computed tomography (CT) may have predictive and prognostic value in management of such patients. Long-term disease control and cure can be achieved in a subgroup of this patient population with low-volume disease relapse who are amenable to potentially curative treatment strategies. Reassuringly, the sensitivity and specificity for recurrence did not significantly vary as a function of the CEA level, suggesting that even with a minimal CEA rise, benefit can be attained by conducting FDG PET-CT in a timely manner.