|
|
|
|
Chemoradiotherapy Tolerability Results in Geriatric Pancreatic Cancer Patients
İrem Sarıcanbaz1, İlknur Kayalı1*, Rahşan Habiboğlu1
1Radiation Oncology Clinic, Ankara Numune Training and Research Hospital, Ankara, Turkey.
Abstract
Pancreatic cancer poses unique challenges in elderly patients, given comorbidities, performance status concerns, and the absence of clear treatment guidelines. Understanding treatment outcomes and tolerability in this age group is vital. In this retrospective study (2012-2019), 24 elderly pancreatic cancer patients (≥65 years) underwent chemoradiotherapy. Patients were categorized into adjuvant or definitive groups, with overall survival (OS) as the primary endpoint. The median follow-up was 13.57 months; the median age was 71.46±5.55 years. Of these, 9 received definitive chemoradiation, while 15 had surgery followed by chemoradiation. Median OS was 13.07 months (definitive) and 23.4 months (adjuvant) (p=0.061). No significant associations were found between OS and radiotherapy doses, pT stage, pN stage, tumor grade, or presence of invasion/microscopic disease. All completed radiotherapy; no grade 4-5 hematologic toxicity occurred. In conclusion, our findings suggest well-tolerated chemoradiotherapy in elderly patients, supporting its use in both adjuvant and definitive settings within this selected patient group.
Keywords: Pancreatic cancer, Chemoradiotherapy, Geriatrics, Aged, Pancreatic neoplasms
Pancreatic adenocarcinoma is a significant cause of cancer-related mortality, particularly in Western countries. Surgical resection offers the only potential cure, but the majority of tumors are unresectable at diagnosis. Despite advances in multimodal therapy, the five-year overall survival (OS) for pancreatic cancer remains dismal at approximately 5%.[1, 2] Standard care for resectable pancreatic cancer involves surgery followed by adjuvant chemotherapy, and the role of postoperative radiotherapy (PORT) continues to be a subject of debate.[3] While some studies demonstrate increased OS with adjuvant radiotherapy,[4-6] others show no clear benefit.[7-9]
For locally advanced unresectable pancreatic cancer, chemoradiation has become an accepted form of definitive treatment. However, this approach is associated with significant treatment-related morbidity and poor outcomes.[10-13] With an aging population globally, the majority of pancreatic cancer patients are over the age of 65. Yet, this age group is underrepresented in clinical trials, and the efficacy and tolerability of treatments in older patients remain unclear. Retrospective studies, like ours, become essential for examining outcomes and tolerability in this elderly cohort.[14] Therefore, we aimed to investigate the treatment outcomes and tolerability of full-dose chemoradiation therapy in patients aged 65 years or older with pancreatic cancer.
Materials and Methods
This retrospective study was conducted at a single radiation oncology center in Turkey, and the protocol was approved by the local ethics committee. Patients aged 65 years or older with curative or adjuvant pancreatic cancer treated with chemoradiation therapy between 2013 and 2018 were retrospectively reviewed. Exclusion criteria included M1 disease, age <65, and histopathologic diagnoses other than ductal adenocarcinomas. Adjuvant external beam radiotherapy was delivered with linear accelerators, and concurrent chemotherapy (CT) was applied with capecitabine or gemcitabine. Statistical analysis was performed using SPSS Statistics 22.0, comparing treatment groups with various tests.
We analyzed 24 patients, with 9 in the definitive group and 15 in the adjuvant group. The median follow-up was 13.57 months, and the median age was 71.46±5.55 years. In the definitive group, the median age and the dose of RT were significantly higher compared to the adjuvant group. No differences were observed in ECOG, gender, CT given with RT, and the number of CT given before RT or RT technique. Tumor characteristics varied between the groups, with the majority located in the pancreatic head for the adjuvant group and in the corpus for the definitive group. Patient characteristics are shown in Table 1 and tumor characteristics of the patients are listed in Table 2.
Table 1. Patient and Treatment Characteristics |
|||
|
Characteristic |
Definitive |
Adjuvan |
P |
|
|
(n=9) |
(n= 15) |
value |
|
Median age (y) |
73±7.4 |
70.53±4.1 |
0.017 |
|
Gender |
|
|
0.74 |
|
Female |
33.33%(3/9) |
40%(6/15) |
|
|
Male |
67.67%(6/9) |
60%(9/15) |
|
|
Pre-CRT ECOG |
|
|
0.643 |
|
0 |
11.11% (1/9) |
13.33% (2/15) |
|
|
1 |
56.56% (5/9) |
66.67% (10/15) |
|
|
2 |
33.33% (3/9) |
20.00% (3/15) |
|
|
CT given with RT |
|
|
0,339 |
|
gemcitabine |
77.78% (7/9) |
66.67% (10/15) |
|
|
Capacitabine |
22.22% (2/9) |
20.00% (3/15) |
|
|
none |
- |
13.33% (2/15) |
|
|
CT given before RT |
|
|
0,326 |
|
1-4 |
44.44% (4/9) |
73.33% (11/15) |
|
|
5-6 |
33.33% (3/9) |
20.00% (3/15) |
|
|
none |
22.22% (2/9) |
6.67% (1/15) |
|
|
RT dose (Gy) |
|
|
0.039 |
|
45 |
11.11% (1/9) |
53.33% (8/15) |
|
|
50.4 |
88.89% (8/9) |
46.67% (7/15) |
|
|
RT mean dose (Gy) |
49.8 |
47.52 |
0,04 |
|
RT technique |
|
|
0.57 |
|
3D conformal |
77.78% (7/9) |
86.67% (13/15) |
|
|
IMRT |
22.22% (2/9) |
13.33% (2/15) |
|
Abbreviations: CRT=chemoradiotherapy; ECOG= Eastern Cooperative Oncology Group; IMRT= intensity-modulated radiation therapy; CT= chemotherapy; RT= radiotherapy
Table 2. Tumor Characteristics of Patients |
||
|
Characteristic |
Definitive |
Adjuvan |
|
|
(n= 9 ) |
(n=15 ) |
|
Location in pancreas |
|
|
|
head |
33.33% (3/9) |
86.67% (13/15) |
|
body |
44.44% (4/9) |
00.00% (0/15) |
|
tail |
22.22% (2/9) |
13.33% (2/15) |
|
Tumor diameter (cm) |
3,95±1.097 |
3,65±1.32 |
|
Tumor grade |
|
|
|
Well differantiated |
--- |
13.33% (2/15) |
|
Modarately differantiated |
--- |
60% (9/15) |
|
Poorly differantiated |
--- |
26.67% (4/15) |
|
Stage |
|
|
|
T2 |
- |
6.67% (1/15) |
|
T3 |
44.44% (4/9) |
73.33% (11/15) |
|
T4 |
56.56% (5/9) |
|
|
Lymph nodes |
|
|
|
Positive |
--- |
86.67% (13/15) |
|
Number assessed(median) |
--- |
13 (3-25) |
|
Number positive(median) |
--- |
2(0-18) |
|
LVI |
--- |
46.67% (7/15) |
|
PNI |
--- |
80.00% (12/15) |
|
Surgical Margins |
|
|
|
Pozitive |
--- |
46.67% (7/15) |
Abbreviations: LVI = lymphovascular invasion; PNI = perineural invasion
Toxicity was generally manageable, with no grade 4-5 hematologic toxicity observed. Adverse events were mostly related to treatment, including sickness, vomiting, and lack of appetite. Oral nutritional support was initiated in 20 patients, and no patient required a feeding tube or parenteral nutritional support during treatment.
The median overall survival was 13.07 months in the definitive group and 23.4 months in the adjuvant group, although this difference did not reach statistical significance (p=0.061). Univariate analysis did not reveal significant associations between OS and various factors, including RT dose, pT stage, pN stage, tumor grade, and the presence of lymphovascular invasion (LVI), perineural invasion (PNI), and microscopic disease (Table 3).
Abbreviations: CRT=chemoradiotherapy; ECOG= Eastern Cooperative Oncology Group; LVI = lymphovascular invasion; PNI = perineural invasion; CT= chemotherapy; RT= radiotherapy
Pancreatic adenocarcinoma presents a challenging prognosis across various age groups, with prospective studies indicating a median overall survival (OS) of 17 to 20.1 months.[7, 8, 10, 15, 16] Limited literature focuses on the elderly, often relying on retrospective studies due to constrained treatment options for this demographic.
In our study, the adjuvant group, with a median age of 70.5 years, demonstrated a noteworthy median OS of 23.4 months. In the definitive group, with a median age of 73, the median OS was 13 months. Importantly, the adjuvant group's OS closely resembled values observed in non-elderly cohorts.
Miyamoto et al. investigated pancreatic cancer patients aged 75 or older (n=42) undergoing chemoradiotherapy (CRT) as adjuvant or definitive therapy. They reported a median OS of 20.6 months for those undergoing surgery followed by CRT, comparable to our findings.[17]
Horowitz et al. studied 655 patients, noting improved two-year survival with adjuvant CRT for those ≥75 (49% vs. 31.6%, p=0.013), with similar five-year survival rates.[18] Frakes et al. associated increased mortality in the elderly with specific factors, while our study did not find significant associations between OS and certain parameters in the adjuvant group.[19]
Miyamoto et al. reported adverse events during CRT, with our study showing manageable toxicity and no treatment interruptions.[17] Advanced radiotherapy techniques contribute to reduced toxicity, as suggested by Ciabatti et al.[20]
Despite its limitations – including retrospective design, a small patient cohort, and heterogeneity – our study highlights the tolerability and outcomes of CRT in elderly patients. The results underscore CRT as a viable treatment option for the elderly in both adjuvant and definitive settings within carefully selected patient groups. Ongoing research in treatment strategies aims to achieve improved survival with diminished toxicity.
Conclusion
In conclusion, our study supports the feasibility and tolerability of full-dose chemoradiation therapy for elderly patients with pancreatic cancer. While differences in median overall survival between definitive and adjuvant groups did not reach statistical significance, the comparable outcomes suggest the potential efficacy of this treatment in the elderly cohort. With manageable toxicities and a favorable safety profile, full-dose chemoradiation emerges as a valuable consideration in treatment decisions for elderly patients with pancreatic cancer. Further research in larger cohorts is warranted to validate and refine these findings, paving the way for improved and personalized therapeutic strategies in the management of pancreatic cancer in the elderly.
None.
None.
None.
The protocol was approved by the Ethics Committee of Ankara Numune Training and Research Hospital. (Approval No: E-19-2694, dated 09/05/2019).
|
||||||||
