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Highly proliferative neuroendocrine carcinoma - influence of radiotherapy fractionation on tumor response.

Ree AH - Radiat Oncol (2008)

Bottom Line: The accelerated hyperfractionated radiotherapy appeared to limit the rate of tumor growth to a greater degree than the conventional fractionation schedule.Given the proliferative capacity of poorly differentiated neuroendocrine carcinomas of the gastrointestinal tract, radiotherapy may be a therapeutic supplement to chemotherapy, which represents the main treatment option in this tumor entity.Importantly, tumors with a capacity for rapid proliferation and regeneration may be particularly sensitive to the use of intensified fractionation protocols in clinical radiotherapy.

View Article: PubMed Central - HTML - PubMed

Affiliation: Division of Cancer Medicine and Radiotherapy, The Norwegian Radium Hospital, Rikshospitalet University Hospital, 0310 Oslo, Norway. a.h.ree@medisin.uio.no

ABSTRACT
A 45-year-old white male presented to our department with postoperative recurrence of gastrointestinal poorly differentiated neuroendocrine carcinoma manifesting as lymph node dissemination and a solitary implantation metastasis in the rectovesical pouch. Following disease progression on chemotherapy, the patient was treated with radiotherapy using either a conventional daily treatment or an accelerated hyperfractionated protocol to separate sites of disease progression. Using serial CT scan assessment, changes in cross-sectional area of the separately treated metastatic lesions were evaluated for determination of therapy response. The accelerated hyperfractionated radiotherapy appeared to limit the rate of tumor growth to a greater degree than the conventional fractionation schedule. Of uttermost importance, in this palliative setting, the patient completed the intensified radiotherapy regimens with acceptable acute toxicity. Given the proliferative capacity of poorly differentiated neuroendocrine carcinomas of the gastrointestinal tract, radiotherapy may be a therapeutic supplement to chemotherapy, which represents the main treatment option in this tumor entity. Importantly, tumors with a capacity for rapid proliferation and regeneration may be particularly sensitive to the use of intensified fractionation protocols in clinical radiotherapy.

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Poorly differentiated neuroendocrine carcinoma – progression and therapy response of disease manifestations. Repeated helical CT scannings were accomplished in the course of the disease relapse (when the patient was referred to our institution), which was defined as day 1. On the basis of the diagnostic description of contrast-enhancing lesions in the transverse view, cross-sectional area (the maximum diameter multiplied by perpendicular bisector) of each lesion was calculated, according to the established World Health Organization criteria for evaluation of tumor response to cytotoxic therapy. Filled circles: lesion size at each CT record, determined relative to the cross-sectional area at first appearance (set to the value of 1). Stars: the radiological review at day 492, done by MRI. Thick lines: duration of the therapy regimens. Arrowheads: time for start of chemotherapy cycles. EP: chemotherapy consisting of etoposide and cisplatin. tem: chemotherapy consisting of temozolomide. RT: radiotherapy. TV1: target volume 1 (pathologic retroperitoneal lymph nodes). TV2: target volume 2 (macroscopic pelvic tumor). TV3: target volume 3 (pathologic supraclavicular lymph nodes).
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Figure 1: Poorly differentiated neuroendocrine carcinoma – progression and therapy response of disease manifestations. Repeated helical CT scannings were accomplished in the course of the disease relapse (when the patient was referred to our institution), which was defined as day 1. On the basis of the diagnostic description of contrast-enhancing lesions in the transverse view, cross-sectional area (the maximum diameter multiplied by perpendicular bisector) of each lesion was calculated, according to the established World Health Organization criteria for evaluation of tumor response to cytotoxic therapy. Filled circles: lesion size at each CT record, determined relative to the cross-sectional area at first appearance (set to the value of 1). Stars: the radiological review at day 492, done by MRI. Thick lines: duration of the therapy regimens. Arrowheads: time for start of chemotherapy cycles. EP: chemotherapy consisting of etoposide and cisplatin. tem: chemotherapy consisting of temozolomide. RT: radiotherapy. TV1: target volume 1 (pathologic retroperitoneal lymph nodes). TV2: target volume 2 (macroscopic pelvic tumor). TV3: target volume 3 (pathologic supraclavicular lymph nodes).

Mentions: The patient was referred to our department four months after the abdominal surgery when abdominal-pelvic CT scanning had revealed an enlarged, retroperitoneal lymph node (16 mm × 18 mm in the transverse view) located between the abdominal aorta and inferior vena cava and a lesion with peripheral contrast enhancement and decreased central density (19 mm × 32 mm in the transverse view) located in the rectovesical pouch. Because of waiting time until admittance, a new CT scan was performed (51 days after the previous, which was defined as the day of disease relapse), confirming an additional ≥ 2-fold increases of cross-sectional lesion area (Figure 1). The patient proceeded to ultrasound-guided biopsy confirmation of the retroperitoneal nodal relapse prior to commencing chemotherapy consisting of etoposide (100 mg/m2 daily, on days 1–3) and cisplatin (45 mg/m2 daily, on days 2–3) in 4-week cycles (Figure 1; EP: etoposide/cisplatin). CT evaluation of tumor response was initially performed after every two treatment cycles. Both pathologic lesions showed significant initial responses; however, disease progression was noted at the retroperitoneal region after the sixth cycle (Figure 1), resulting in discontinuation of the etoposide/cisplatin chemotherapy. Following additional CT evidence of disease progression (266 days after the diagnosis of disease relapse), the patient proceeded to second-line temozolomide chemotherapy, according to clinical experience from Uppsala University Hospital in Sweden [8]; however, both the retroperitoneal and the pelvic lesions progressed on this treatment (Figure 1; tem: temozolomide).


Highly proliferative neuroendocrine carcinoma - influence of radiotherapy fractionation on tumor response.

Ree AH - Radiat Oncol (2008)

Poorly differentiated neuroendocrine carcinoma – progression and therapy response of disease manifestations. Repeated helical CT scannings were accomplished in the course of the disease relapse (when the patient was referred to our institution), which was defined as day 1. On the basis of the diagnostic description of contrast-enhancing lesions in the transverse view, cross-sectional area (the maximum diameter multiplied by perpendicular bisector) of each lesion was calculated, according to the established World Health Organization criteria for evaluation of tumor response to cytotoxic therapy. Filled circles: lesion size at each CT record, determined relative to the cross-sectional area at first appearance (set to the value of 1). Stars: the radiological review at day 492, done by MRI. Thick lines: duration of the therapy regimens. Arrowheads: time for start of chemotherapy cycles. EP: chemotherapy consisting of etoposide and cisplatin. tem: chemotherapy consisting of temozolomide. RT: radiotherapy. TV1: target volume 1 (pathologic retroperitoneal lymph nodes). TV2: target volume 2 (macroscopic pelvic tumor). TV3: target volume 3 (pathologic supraclavicular lymph nodes).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2397422&req=5

Figure 1: Poorly differentiated neuroendocrine carcinoma – progression and therapy response of disease manifestations. Repeated helical CT scannings were accomplished in the course of the disease relapse (when the patient was referred to our institution), which was defined as day 1. On the basis of the diagnostic description of contrast-enhancing lesions in the transverse view, cross-sectional area (the maximum diameter multiplied by perpendicular bisector) of each lesion was calculated, according to the established World Health Organization criteria for evaluation of tumor response to cytotoxic therapy. Filled circles: lesion size at each CT record, determined relative to the cross-sectional area at first appearance (set to the value of 1). Stars: the radiological review at day 492, done by MRI. Thick lines: duration of the therapy regimens. Arrowheads: time for start of chemotherapy cycles. EP: chemotherapy consisting of etoposide and cisplatin. tem: chemotherapy consisting of temozolomide. RT: radiotherapy. TV1: target volume 1 (pathologic retroperitoneal lymph nodes). TV2: target volume 2 (macroscopic pelvic tumor). TV3: target volume 3 (pathologic supraclavicular lymph nodes).
Mentions: The patient was referred to our department four months after the abdominal surgery when abdominal-pelvic CT scanning had revealed an enlarged, retroperitoneal lymph node (16 mm × 18 mm in the transverse view) located between the abdominal aorta and inferior vena cava and a lesion with peripheral contrast enhancement and decreased central density (19 mm × 32 mm in the transverse view) located in the rectovesical pouch. Because of waiting time until admittance, a new CT scan was performed (51 days after the previous, which was defined as the day of disease relapse), confirming an additional ≥ 2-fold increases of cross-sectional lesion area (Figure 1). The patient proceeded to ultrasound-guided biopsy confirmation of the retroperitoneal nodal relapse prior to commencing chemotherapy consisting of etoposide (100 mg/m2 daily, on days 1–3) and cisplatin (45 mg/m2 daily, on days 2–3) in 4-week cycles (Figure 1; EP: etoposide/cisplatin). CT evaluation of tumor response was initially performed after every two treatment cycles. Both pathologic lesions showed significant initial responses; however, disease progression was noted at the retroperitoneal region after the sixth cycle (Figure 1), resulting in discontinuation of the etoposide/cisplatin chemotherapy. Following additional CT evidence of disease progression (266 days after the diagnosis of disease relapse), the patient proceeded to second-line temozolomide chemotherapy, according to clinical experience from Uppsala University Hospital in Sweden [8]; however, both the retroperitoneal and the pelvic lesions progressed on this treatment (Figure 1; tem: temozolomide).

Bottom Line: The accelerated hyperfractionated radiotherapy appeared to limit the rate of tumor growth to a greater degree than the conventional fractionation schedule.Given the proliferative capacity of poorly differentiated neuroendocrine carcinomas of the gastrointestinal tract, radiotherapy may be a therapeutic supplement to chemotherapy, which represents the main treatment option in this tumor entity.Importantly, tumors with a capacity for rapid proliferation and regeneration may be particularly sensitive to the use of intensified fractionation protocols in clinical radiotherapy.

View Article: PubMed Central - HTML - PubMed

Affiliation: Division of Cancer Medicine and Radiotherapy, The Norwegian Radium Hospital, Rikshospitalet University Hospital, 0310 Oslo, Norway. a.h.ree@medisin.uio.no

ABSTRACT
A 45-year-old white male presented to our department with postoperative recurrence of gastrointestinal poorly differentiated neuroendocrine carcinoma manifesting as lymph node dissemination and a solitary implantation metastasis in the rectovesical pouch. Following disease progression on chemotherapy, the patient was treated with radiotherapy using either a conventional daily treatment or an accelerated hyperfractionated protocol to separate sites of disease progression. Using serial CT scan assessment, changes in cross-sectional area of the separately treated metastatic lesions were evaluated for determination of therapy response. The accelerated hyperfractionated radiotherapy appeared to limit the rate of tumor growth to a greater degree than the conventional fractionation schedule. Of uttermost importance, in this palliative setting, the patient completed the intensified radiotherapy regimens with acceptable acute toxicity. Given the proliferative capacity of poorly differentiated neuroendocrine carcinomas of the gastrointestinal tract, radiotherapy may be a therapeutic supplement to chemotherapy, which represents the main treatment option in this tumor entity. Importantly, tumors with a capacity for rapid proliferation and regeneration may be particularly sensitive to the use of intensified fractionation protocols in clinical radiotherapy.

Show MeSH
Related in: MedlinePlus