Background
Pancreatic ductal adenocarcinoma (PDAC) is the third most frequent cause of cancer-related deaths in Western countries and is predicted to become the second leading cause within the next 10 years.1,2 Pancreatectomy and systemic therapy maximize curative potential for individuals with localized pancreatic cancer (LPC). The median overall survival (OS) of the most highly selected patients treated with both approaches 4 years.3 However, most patients who undergo pancreatectomy are not cured. As many as 25% of patients who undergo pancreatectomy de novo do not survive for 1 year, and 69% to 75% of patients experience relapse within 2 years.4–7 Improving quality of life and prolonging meaningful longevity are thus both treatment priorities in this population.
Systemic chemotherapy is increasingly being administered to patients with LPC as first-line therapy. This strategy provides opportunities to measure and optimize each patient’s physiologic status, to challenge the inherent biology of their cancer, to establish which patients are likely to benefit from subsequent local therapies, and to prolong the survival of those who are not.8–10 Previously used primarily for patients with locally advanced cancer in whom pancreatectomy was not anticipated, first-line chemotherapy is now preferred in the ASCO guidelines for patients with locally invasive tumors, those with clinical findings suggestive of advanced disease, and those with a marginal physiologic status, and is suggested as a reasonable option even for patients who may otherwise be surgical candidates at presentation.11 Recent, large “real-world” series have shown that 5% to 41% of unselected patients with LPC who are treated initially with chemotherapy undergo subsequent pancreatectomy.3,8–10
Although systemic chemotherapy represents a cornerstone of therapy for most patients with LPC, clinical indicators of response to chemotherapy—which is typically measured histopathologically in resected surgical specimens and may be used to provide prognostic information and inform the delivery of subsequent treatments—have been poorly characterized in this population. We previously reported that changes in radiographic tumor volume and serum CA 19-9 levels represent a readout of histopathologic response among patients who are treated with preoperative chemotherapy and pancreatectomy.12 We hypothesized that these same indicators may, similarly, provide clinically relevant information for patients whose primary tumors are not removed and for whom histopathologic response thus cannot be measured. Here, we evaluated the association between putative serologic and radiographic measures of therapeutic response and survival among patients with LPC who were treated with first-line chemotherapy and who did not subsequently undergo pancreatectomy.
Methods
Following Institutional Review Board (IRB) approval at The University of Texas MD Anderson Cancer Center (MDACC; IRB PA 18-1093), we queried our prospectively maintained pancreatic tumor database and identified 619 consecutive patients who we evaluated for localized, previously untreated PDAC between January 1, 2010, and December 31, 2017, and who we treated initially with chemotherapy, with or without anticipation of subsequent pancreatectomy.11 The requirement for individual informed consent was waived by the IRB due to the retrospective nature of the study. We excluded 290 patients: 24 who had metastatic progression during the first-line chemotherapy, 126 who subsequently underwent pancreatectomy, 75 who were lost to follow-up or did not have sufficient pretreatment imaging to perform volumetric analysis, 38 who received <3 doses of chemotherapy, 24 who were CA 19-9 nonproducers, and 3 who had radiographic evidence of acute pancreatitis (Figure 1).
Study flow diagram.
Abbreviations: FOLFIRINOX, 5-fluorouracil/leucovorin/oxaliplatin/irinotecan; Gem/Nab-paclitaxel, gemcitabine + nanoparticle albumin–bound paclitaxel; PDAC, pancreatic ductal adenocarcinoma.
Citation: Journal of the National Comprehensive Cancer Network 20, 8; 10.6004/jnccn.2022.7018
Study flow diagram.
Abbreviations: FOLFIRINOX, 5-fluorouracil/leucovorin/oxaliplatin/irinotecan; Gem/Nab-paclitaxel, gemcitabine + nanoparticle albumin–bound paclitaxel; PDAC, pancreatic ductal adenocarcinoma.
Citation: Journal of the National Comprehensive Cancer Network 20, 8; 10.6004/jnccn.2022.7018
Study flow diagram.
Abbreviations: FOLFIRINOX, 5-fluorouracil/leucovorin/oxaliplatin/irinotecan; Gem/Nab-paclitaxel, gemcitabine + nanoparticle albumin–bound paclitaxel; PDAC, pancreatic ductal adenocarcinoma.
Citation: Journal of the National Comprehensive Cancer Network 20, 8; 10.6004/jnccn.2022.7018
All patients included in the analysis had available pretreatment multidetector CT (MDCT) imaging performed using a 64‐detector row scanner with a standard protocol optimized for imaging pancreatic tumors. Because radiographic and serologic changes were integral to the study design, patients for whom a sufficient pretreatment CT scan was not available and those who were CA 19-9 nonproducers were excluded.
First-Line Chemotherapy Regimens
Systemic chemotherapy consisted of 5-fluorouracil/leucovorin/oxaliplatin/irinotecan (FOLFIRINOX) administered every 2 weeks or gemcitabine + nab-paclitaxel administered in either 4-week or 2-week intervals. These were reported in terms of doses. MDACC’s preference is to administer both regimens twice each month. Nine patients had chemotherapy administered using an alternate cycle (ie, 2 doses in a 3-week cycle or 3 doses in a 4-week cycle). Baseline performance status of all patients was defined at presentation using the ECOG system.13 All tumors were restaged within 4 to 8 weeks after completion of first-line therapy. The duration of chemotherapy was individualized and based on response to and tolerance of treatment.
Radiographic Measures of Response
Before initiation of first-line chemotherapy and following its completion, anatomic cancer staging was performed using an MDCT scan.14 Multiplanar reconstruction was used as necessary to visualize vascular anatomy. Per standardized criteria, tumors were radiographically staged as potentially resectable, borderline resectable, or locally advanced.15
Retrospective volumetric analysis was performed and rereviewed by a single surgeon (G. Perri), who was blinded to treatment and outcome. The examiner measured the tumor size in its longest (L) and shortest (W) axial diameters and its craniocaudal diameter (H). The volume of each tumor was calculated according to the formula for a typical ellipsoid (volume = π/6×L×W×H).16 To characterize radiographic changes associated with first-line therapy for each patient, the volume of the primary tumor calculated on pretreatment image review was compared with the volume on posttreatment image review. The percentage change in tumor volume (%Δvol) was calculated as a percentage of the baseline volume. A positive value signified a decrease in tumor volume and a negative value signified an increase in tumor volume following chemotherapy. Changes were also described using modified RECIST version 1.1.17 Progressive disease was defined as local progression with an increase of at least 20% in the primary tumor’s largest dimension (with a minimum increase of 5 mm). A partial response was defined as a decrease of at least 30% in the primary tumor’s largest dimension. Stable disease was defined as an increase or decrease in tumor size insufficient to qualify as progressive disease or partial response. A complete response was defined as total disappearance of the primary tumor.
Serologic Measure of Response
Serum CA 19-9 levels (normal range, 0–37 U/mL) were measured before and after treatment. Patients whose posttreatment CA 19-9 level decreased from the pretreatment value were considered serologic responders. Patients whose posttreatment CA 19-9 level remained elevated or increased from the pretreatment value were considered serologic nonresponders. Patients whose CA 19-9 level was <1 U/mL both before and after treatment were defined as nonproducers and had been excluded.
Combined Response Categories
We created 3 clinical categories based on combined radiographic and serologic response metrics (1) best responders: patients who had a decrease in tumor volume on radiographic restaging within the top quartile of all patients and a CA 19-9 decrease following first-line therapy; (2) nonresponders: patients who had an increase in tumor volume on radiographic restaging and a CA 19-9 increase following first-line therapy; and (3) all other patients: patients who had a decrease in tumor volume on radiographic restaging placing them below the top quartile with or without a CA 19-9 decrease or if tumor volume increased with a CA 19-9 decrease. These groups prioritized tumor volume based on prior publications showing that %Δvol is a more sensitive measurement of radiographic response than RECIST criteria, and specified cutoffs were established using the analysis described herein.3,18
Statistical Analysis
Continuous data were expressed as medians and interquartile ranges and were compared between response groups using the Kruskal-Wallis test. Categoric data were expressed as frequencies and percentages and were compared between response groups using the chi-square test. Survival analysis was performed using the Kaplan-Meier method with univariate log-rank analysis. OS was defined as the time from the date of diagnosis to the date of death or censored at the date of last follow-up. All clinically relevant variables that were statistically significant on univariable analysis were entered into a multivariable model. A stratified Cox proportional hazard regression model was used to evaluate the ability of prognostic variables to predict OS. Clinical factors with a P value <.2 on univariable analysis and those that had potential clinical importance were included in the Cox model. All tests were 2-sided and performed at the 5% significance level. Statistical analysis was performed using the STATA, version 14.2 (StataCorp LP).
Results
A total of 329 patients completed at least 3 doses of FOLFIRINOX or gemcitabine + nab-paclitaxel and had radiographically localized disease at subsequent restaging.
Clinical Features of Patients Who Did Not Undergo Pancreatectomy
The clinicopathologic profile of all 329 patients is reported in Table 1. Most patients were male (54%), and the median age at diagnosis was 66 years (interquartile range [IQR], 59–72 years). Most patients (91%) had an ECOG performance status of 0 to 1. Median baseline CA 19-9 level was 331 U/mL (IQR, 74–931 U/mL). Seventy-two percent of tumors were in the pancreatic head or neck, and 28% were located in the body or tail. Thirty percent of tumors were potentially resectable, 28% were borderline resectable, and 42% were locally advanced per radiographic criteria. FOLFIRINOX was administered to 55% of patients and gemcitabine + nab-paclitaxel to 45%, with a median of 6 (IQR, 4–8) doses.
Clinical Profiles of Patients Who Did Not Undergo Pancreatectomy
Table 2 reports putative metrics of response to first-line chemotherapy. According to RECIST, 269 (82%), 39 (12%), and 21 (6%) patients experienced stable disease, partial response, and progressive disease following first-line chemotherapy, respectively. The volume of 232 (70%) patients’ tumors decreased following first-line chemotherapy, with a median reduction in tumor volume of 21% (IQR, −11% to 42%). The serum CA 19-9 level in 246 patients (75%) decreased following first-line chemotherapy, whereas that of 77 patients (25%) did not. The median posttreatment CA 19-9 level was 101 U/mL (IQR, 33–411 U/mL).
Metrics of Response to First-Line Chemotherapy in Patients Who Did Not Undergo Pancreatectomy
Radiographic Measure of Response and Association With Survival
Patients were stratified by %Δvol after therapy, as shown in supplemental eFigure 1 (available with this article at JNCCN.org), into 4 quartiles (1: tumor volume increase of >8%; 2: tumor volume increase of 8% to a tumor volume decrease of 21%; 3: tumor volume decrease of 22% to 41%; and 4: tumor volume decrease of >41%) (Figure 2A). For quartiles 1, 2, 3, and 4, the median OS durations were 12, 16, 18, and 22 months, respectively. Significant differences in median OS were found between patients in quartile 4 (greatest response) and those in all other quartiles (all P<.02; Figure 2B). In addition, median OS was significantly shorter in patients in the bottom quartile (quartile 1) than in all other quartiles (P≤.01). There was no significant difference in median OS between patients in quartiles 2 and 3.
Measures of radiographic response. Proportion of patients grouped by (A) quartile of tumor volume change versus (C) RECIST 1.1 standard categories. (B) Median overall survival of patients stratified by posttreatment radiographic tumor volume quartile was 12, 16, 18, and 22 months for quartiles 1, 2, 3, and 4, respectively. (D) Median overall survival of patients stratified by RECIST 1.1 criteria was 12, 18, and 22 months for patients with PD, SD, and PR, respectively.
Abbreviations: PD, progressive disease; PR, partial response; Q, quartile; SD, stable disease.
Citation: Journal of the National Comprehensive Cancer Network 20, 8; 10.6004/jnccn.2022.7018
Measures of radiographic response. Proportion of patients grouped by (A) quartile of tumor volume change versus (C) RECIST 1.1 standard categories. (B) Median overall survival of patients stratified by posttreatment radiographic tumor volume quartile was 12, 16, 18, and 22 months for quartiles 1, 2, 3, and 4, respectively. (D) Median overall survival of patients stratified by RECIST 1.1 criteria was 12, 18, and 22 months for patients with PD, SD, and PR, respectively.
Abbreviations: PD, progressive disease; PR, partial response; Q, quartile; SD, stable disease.
Citation: Journal of the National Comprehensive Cancer Network 20, 8; 10.6004/jnccn.2022.7018
Measures of radiographic response. Proportion of patients grouped by (A) quartile of tumor volume change versus (C) RECIST 1.1 standard categories. (B) Median overall survival of patients stratified by posttreatment radiographic tumor volume quartile was 12, 16, 18, and 22 months for quartiles 1, 2, 3, and 4, respectively. (D) Median overall survival of patients stratified by RECIST 1.1 criteria was 12, 18, and 22 months for patients with PD, SD, and PR, respectively.
Abbreviations: PD, progressive disease; PR, partial response; Q, quartile; SD, stable disease.
Citation: Journal of the National Comprehensive Cancer Network 20, 8; 10.6004/jnccn.2022.7018
The relationship between RECIST 1.1 response categories (Figure 2C) and survival is shown in Figure 2D. Patients who experienced progressive disease had significantly shorter median OS (12 months) than patients with stable disease and those with a partial response (18 and 22 months, respectively; P<.01). There was no statistically significant difference in OS between patients with stable disease and those with a partial response (P=.10).
Serologic Measure of Response and Association With Survival
Figure 3A depicts the distribution of changes in CA 19-9 levels from baseline to posttreatment for the entire cohort. Figure 3B compares the OS durations of patients who had a CA 19-9 increase or decrease. Patients who experienced a decrease in CA 19-9 level had significantly longer median OS than those who experienced an increase (19 vs 14 months; P<.01).
Serologic measure of response. (A) Distribution of changes in CA 19-9 levels from baseline to posttreatment. (B) Overall survival of patients whose posttreatment CA 19-9 level increased from baseline (median, 14 months) versus those whose posttreatment CA 19-9 level decreased from baseline (median, 19 months; P<.01).
Citation: Journal of the National Comprehensive Cancer Network 20, 8; 10.6004/jnccn.2022.7018
Serologic measure of response. (A) Distribution of changes in CA 19-9 levels from baseline to posttreatment. (B) Overall survival of patients whose posttreatment CA 19-9 level increased from baseline (median, 14 months) versus those whose posttreatment CA 19-9 level decreased from baseline (median, 19 months; P<.01).
Citation: Journal of the National Comprehensive Cancer Network 20, 8; 10.6004/jnccn.2022.7018
Serologic measure of response. (A) Distribution of changes in CA 19-9 levels from baseline to posttreatment. (B) Overall survival of patients whose posttreatment CA 19-9 level increased from baseline (median, 14 months) versus those whose posttreatment CA 19-9 level decreased from baseline (median, 19 months; P<.01).
Citation: Journal of the National Comprehensive Cancer Network 20, 8; 10.6004/jnccn.2022.7018
Clinical Features and Metrics of Response to First-Line Chemotherapy Stratified by Response Category
The clinicopathologic features of patients stratified by combined response category are reported in Table 3. A total of 73 patients (22%) were classified as best responders, 214 (65%) as others, and 42 (13%) as nonresponders.
Clinical Features and Metrics of Response to First-Line Chemotherapy Stratified by Response Category (N=329)
There were no statistical differences in sex, age, body mass index, ECOG performance status, tumor site, or clinical stage between these cohorts. There were also no differences in baseline CA 19-9 measurement between cohorts, with a median CA 19-9 level of 237 U/mL (IQR, 74–747 U/mL) for best responders, 340 U/mL (range, 82–1,001 U/mL) for others, and 429 U/mL (range, 41–834 U/mL) for nonresponders (P=.60). A greater proportion of nonresponders received FOLFIRINOX than did patients in the other 2 cohorts (71% vs 58% and 51%, respectively; P=.04). Best responders received a higher median number of chemotherapy doses (median, 8; IQR, 5–10) than other patients (median, 6; IQR, 4–8) and nonresponders (median, 4; IQR, 3–5; P<.01).
The differences in median %Δvol and RECIST 1.1 stratification between response categories are shown in Table 3. Supplemental eFigure 2 shows the distribution of changes in CA 19-9 from baseline to posttreatment stratified by response category.
Overall Survival
Figure 4B shows OS stratified by response category. Best responders experienced significantly longer median OS (24 months) than other patients (17 months; P=.02) and nonresponders (12 months; P<.01).
Relationship of response categories and receipt of RT with OS. (A) Median OS of patients stratified by combined response category. (B) Median OS of best responders and others/nonresponders stratified by receipt of RT.
Abbreviations: BR, best responders; NR, nonresponders; OP, other patients; OS, overall survival; RT, radiotherapy.
Citation: Journal of the National Comprehensive Cancer Network 20, 8; 10.6004/jnccn.2022.7018
Relationship of response categories and receipt of RT with OS. (A) Median OS of patients stratified by combined response category. (B) Median OS of best responders and others/nonresponders stratified by receipt of RT.
Abbreviations: BR, best responders; NR, nonresponders; OP, other patients; OS, overall survival; RT, radiotherapy.
Citation: Journal of the National Comprehensive Cancer Network 20, 8; 10.6004/jnccn.2022.7018
Relationship of response categories and receipt of RT with OS. (A) Median OS of patients stratified by combined response category. (B) Median OS of best responders and others/nonresponders stratified by receipt of RT.
Abbreviations: BR, best responders; NR, nonresponders; OP, other patients; OS, overall survival; RT, radiotherapy.
Citation: Journal of the National Comprehensive Cancer Network 20, 8; 10.6004/jnccn.2022.7018
A Cox regression model was developed to evaluate potential predictors of OS (Table 4). The number of chemotherapy doses and combined response category were each independently associated with survival. A higher number of chemotherapy doses was associated with longer survival (hazard ratio [HR], 0.94; 95% CI, 0.89–0.98). Best responders (HR, 0.35; 95% CI, 0.21–0.58) and other patients (HR, 0.55; 95% CI, 0.37–0.83) had longer survival than nonresponders. The cumulative effect of the combined response cohort did show an additive effect on survival that was stronger than that contributed by either CA 19-9 reduction (HR, 0.65; 95% CI, 0.47–0.91) or tumor volume decrease (HR, 0.63; 95% CI, 0.44–0.88) in a multivariable regression model (supplemental eTable 1).
Univariable and Multivariable Cox Proportional Hazards Regression Analysis of Overall Survival for Patients With Unresected Localized PDAC (N=329)
Local Therapy Following First-Line Chemotherapy
There was no statistically significant difference in the rates at which radiation therapy was subsequently delivered to any cohort (34% for best responders, 37% for other patients, and 19% for nonresponders; P=.07). Additionally, there was no significant difference in median OS between best responders who were not treated with radiation (22 months) compared with those who were (26 months; P=.62) or between other patients and nonresponders who were not treated with radiation (16 months) and those who were (17 months; P=.37) (Figure 4B).
Discussion
We previously showed that changes in radiographic tumor volume and serum CA 19-9 level represent clinical signals of chemotherapeutic effect that correspond to those measured histopathologically in resected specimens.12 In this study, we present additional evidence that these indicators provide clinically relevant information in patients with LPC who were initially treated with systemic chemotherapy but did not undergo pancreatectomy and for whom no histopathologic specimens exist. Among these patients, best responders (those whose tumors had a reduction in volume within the top quartile and who had a decline in CA 19-9 following induction chemotherapy) lived for a median of 24 months—significantly longer than patients who had less robust changes in their metrics in our study and comparable to all-stage OS durations of resected PDAC nationally.19–22 Thus, longitudinal analysis of dynamic changes in radiographic tumor volume and serum CA 19-9 level appear to provide a surrogate for posttreatment staging when pathologic specimens are not available, helping to stratify patients’ expected outcomes by their tumors’ inherent biology, guide selection of additional therapies, support trial decisions, and provide real-world expectations to patients and families.
The differences in response to first-line chemotherapy identified in this study illustrate the heterogeneity and complexity of the LPC phenotypic landscape. Survival following treatment varies widely for patients with LPC, and many efforts are focused on characterizing and describing the prognostic implications of this variability and the genetic profiles that underlie it.23,24 Unfortunately, few readily accessible, objective clinical indicators can be used to inform assessments of underlying tumor biology or response to therapy. The absence of such markers makes decisions regarding treatment type and duration difficult and, in many cases, leads to the use of local therapies that may cause morbidity in individuals who are unlikely to benefit from them.8,25 The lack of easily interpretable clinical markers of response also reduces providers’ ability to have data-driven discussions with patients regarding expectations of survival and goals of care. Such discussions, as well as those regarding changes in treatment regimen, implementation of aggressive local therapies, and shifting goals of treatment altogether require accurate measurements of treatment response. Although clinical staging provides a starting point for initiation of first-line chemotherapy, it is the dynamic nature of response to first-line chemotherapy that gives the true representation of “tumor biology” and prognosis. Thus, the findings of this study could help orient patients and providers to anticipated outcomes.
Historically, treatment response has been assumed in patients whose tumors exhibit absence of radiographic progression (instead of, for example, presence of regression) following treatment with preoperative therapy, and prior studies have focused on the apparent failure of radiographic changes to predict surgical resectability.26,27 We previously demonstrated that RECIST response is not a robust indicator of resectability among patients with borderline resectable pancreatic cancer, and demonstrated that a higher degree of volumetric response, rather than the presence of any volumetric decrease, was most predictive of major pathologic response.18 It is this prior work that led us to stratify volumetric response in an effort to create a more reproducible system with greater correlative potential. Here we provide further evidence to show that tumor volume (but not RECIST) does provide a readout of tumor chemosensitivity and response in patients with LPC receiving first-line chemotherapy.12 Tumor volume is likely superior to RECIST because it is calculated using 3, instead of 2, measured dimensions and may therefore better reflect subtle morphologic changes within the tumor. Further, RECIST classifies responders into somewhat arbitrary groups using cutoff values, whereas tumor volume is a continuous variable.
We also evaluated CA 19-9 level, which is one of the best available measures of tumor control or progression during induction chemotherapy in this setting.28–35 One prior study reported that a CA 19-9 value that decreases by 40% from its pretreatment value is associated with increased long-term survival following resection. In contrast, patients who undergo surgery without a decrease in CA 19-9 have a median survival duration no different from that of patients treated with chemotherapy alone.28 Here, we found that among patients with unresected LPC a decrease in CA 19-9 level after chemotherapy was associated with longer survival than were stable or increased CA 19-9 levels. The most important limitation of CA 19-9 in this setting is that it is not reliably produced by all patients, and evaluating response may be particularly difficult among nonproducers. More sensitive biomarkers are thus needed. There is growing optimism about the potential for measurements of circulating tumor DNA (ctDNA) in the peripheral and portal venous blood to better quantify systemic disease burden in PDAC.25,36–44 It is reasonable to anticipate a wider integration of these tests into clinical practice in the future, and when combined with radiographic response, they may enable a more reliable assessment of tumor biology.
Overall, fewer than half of patients with LPC who are treated with systemic chemotherapy undergo pancreatectomy.3,19,45,46 Nonetheless, the focus of most available analyses is on identification of factors that predict survival among LPC patients who have undergone surgery. Few, if any, studies have focused on the predictors of longevity in the majority of patients who are treated nonoperatively. We feel this reflects a bias within the medical literature that inappropriately asserts surgical resection as the “goal” of therapy for all patients with PDAC, irrespective of their clinical profile. The lack of reported outcomes stratified by response to chemotherapy in patients with LPC fails to acknowledge the “successes” that can be achieved with chemotherapy or the heterogeneity that exists among patients with LPC. Indeed, best responders in the unselected population reported here had a median OS duration (24 months) that compares favorably to those reported among surgical patients in historic series and trials, even though our cohort consisted of patients who were generally felt to be poor candidates for surgery.19–22
This study has limitations, including those inherent in its retrospective, single-institution design. Two separate chemotherapy regimens were used, which could have introduced heterogeneity into the cohort, but the 2 regimens were associated with similar survival outcomes in a randomized trial.47 We evaluated objective radiographic and serologic metrics that members of our team had previously found to be clinically significant. However, as discussed earlier, there is increasing evidence that other biomarkers such as ctDNA may have greater sensitivity for staging and measuring response to therapy in PDAC, but we did not have ctDNA data for the patients in this study. Other radiographic modalities, such as radiomics, have been described as clinically and biologically relevant tools that could be used in treatment response; however, such analysis was outside the scope of this study.48 We also did not consider the extent to which other factors, such as genomics, may have affected the response to first-line chemotherapy and long-term outcomes. Additionally, this study was not intended to provide data to guide the choice of the next course of treatment or consideration of additional therapies, but rather to show that patients with unresected LPC represent a heterogeneous group and that further investigations are warranted to determine additional therapies stratified by response group. Despite these limitations, this study represents the OS outcomes of a large contemporary cohort of unresected patients treated up-front with modern chemotherapy, providing data on realistic expectations for providers, patients, and families.
Conclusions
Evaluating response to first-line chemotherapy in the setting of LPC is essential to understanding tumor biology and assessing patients’ likely survival outcomes. Changes in tumor volume and serum CA 19-9 levels—but not RECIST 1.1 response status—represent reliable metrics of response to systemic chemotherapy, and here we establish that they can be used as putative predictors of survival in patients with LPC who do not undergo pancreatectomy. Longitudinal, dynamic data analysis could identify surrogates for pathologic staging in the absence of specimen review, stratify patients by their tumor biology, provide realistic prognostic information to patients, and guide additional therapies and trial decisions.
Acknowledgments
We thank Amy Ninetto, Scientific Editor, Research Medical Library, The University of Texas MD Anderson Cancer Center, for editing this manuscript.
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