Role Of Pet/CT In Assessment Of Ovarian Cancer Recurrence

Case Presentation

Case 1

52 years female patient with historical of treated ovary cancer went TAH with BCO and received chemotherapy. Now presented with elevation CA25 and referred for Pet/CT.

Figure (1) Axial ECT of the abdomen (A) Axial Pet image of the abdomen (B) fusion Pet/ CT (C) show peritoneum soft lesions (arrows) which shows hypermetabolism activation on Pet/CT consisting with peritoneum depositing.

The patient proving to be positive for ovary cancer recurrent on clinical and radiology following up.

Case 2

35 years female patient receiving chemotherapeutic medications for treating of metastases cancer ovarian and achieving complete response. Now patient is referring for following up by Pet/CT for suspicious recurrent.

Figure (2) Axially ECT of the abdomen (A) Axially Pet imaging of abdomen (B) and fusion axial Pet/CT image (C) whole Pet mage (D) show FDG hypodensity hepatological focality suggestive of metastatic depositing (red arrow). FDG porta hepatic lymph nodal is noted (black arrow).

Clinical and radiology following up of patient was consisting with recurrence malignancy lesions.

Case 3

29 years female patient went TAH with BCO with and received chemotherapeutic modalities for treatment of ovary cancer. Now patient presented with elevation CA25 and suspicion recurrent. Contrast CT and Pet/CT have been done.

Figure (3) Axially Contrast CT of abdominal area (A) and fusion axial Pet/CT image of abdominal area (B) show pelvis mass lesion (arrows) with metabolism activation seen within consistency with local recurrent.

Histopathology resulting in lesion consisting of local ovary cancer recurrent.

Case 4

46 years female patient went total underwent totally abdomen hysterectomy and bilaterally salpingostomyophrectomy and receiving chemotherapeutic modalities for treating of ovary cancer and the patient achieving complete remitting elevating CA 25. The patient has been referred for Pet/CT.

Figure (4) Fusion Pet/CT images show FDG right external iliac, rectal and left paraaortic FDG lymph nodal (arrows) consistency with node metastases depositions.

The patient has been proving to be positively for ovary cancer recurrent at time of the Pet/CT study by clinically, laboratory and radiology following up of node metastases depositions.

Case 5

65 years female patient had historical of ovary cancer went pan hysterectomy & BCO following by chemotherapeutic modalities and achieving complete remitting. Now patient has clavicular node. Patient referred for Pet/CT.

Figure (5) Axially ECT images of neck and upper chest (A, C) Axially fusing Pet / CT images of neck and chest (B, D) show clavicular with tiny right tracheal FDG nodes (arrows) consisting with nodal metastases depositions.

Histopathological lymph nodal biopsy was consisting with ovary cancer nodes metastases depositions.

Case 6

53 years female patient went pan hysterectomy with BCO and received chemotherapeutics for treating of ovary cancer. Now patient is presenting with elevated CA 25 and referring to Pet/CT.

Figure (6) Axially ECT and fused Pet /CT images show multiplicity of lumbar hypermetabolism peritoneum lesions (arrows) consisting with metastases depositions.

Following up of lesions confirming the diagnostic peritoneum metastases depositions.

Case 7

51 years female patient with history of treated ovary cancer went TAH with BCO and receiving chemotherapeutics. The patient achieving complete remitting. Now patient is presented with elevation CA 25 and referred for Pet/CT.

Figure (7) Whole ECT (A) whole fusion Pet/CT images (B) showing no active locally tumoral recurrent, nodes or peritoneum depositions. The Pet/CT study is consistent with sustaining complete remitting.

Following up of the patient for 6 months after the Pet/CT study was consisting with sustaining complete remitting with no evidence recurrence.

Case 8

77 years female patient with history of treating ovary cancer, went TAH with BCO and received chemotherapy. Patient referred for following up by Pet/CT.

Figure (8) Fusion Axially Pet/CT images of the abdominal area shows hypermetabolism FDG left peritoneum mass (red arrow). Hypermetabolism FDG left aortic nodal (white arrow) is also noted. Pet/CT is consisting with positively recurrent.

Ovary cancer recurrent has been confirming by clinical and radiology following up.

Case 9

43 years female patient went pan hysterectomy with BCO and received chemotherapeutics for treating of ovary cancer. Now patient has elevation CA25. ECT equivocal and patient referring for Pet/CT.

Figure (9) Axially ECT image (A) and axially fusing axially Pet/CT image (B) show FDG peritoneum lesion adhering to a small bowel loop consisting with peritoneum depositions (arrow).

Following up of the patient confirming diagnosis of peritoneum metastases depositions.

Case 10

66 years female patient with history of hysterectomy and bilateral salpingoophorectomy for managing malignancy ovary mass. Patient has history of receiving hormones therapeutics. Patient presented with painful pelvis. ECT revealing suspicion of pelvis masses and patient referring for Pet/CT.

Figure (9) Axially ECT images (A) show (arrow). Fusion Pet/CT images (B) shows physiologic up taking in the adnexa lesion (arrow) which is consisting with stimulation ovary remaining syndrome.

Histopathology result of this lesion was consistent with benign ovarian tissue.

Discussion

The ovary cancer is primary treated with reductive surgical and Chemotherapeutic modalities. Cases with stage 1 or higher usually receive chemotherapeutics. In the period of treatment patients are following with serial measuring of CA25, contrast CT and MR scans. (Charlotte et al., 2014)

Relapse following surgical and first line chemotherapeutics have been seen in 50% percentage of patients on treatment. The recurrent usually occurring in 4 main shapes which are: pelvis masses, peritoneum depositions, malignancy adenopathy and to lesser extension as distant organic metastasis (hepatic metastatic are usually common). (Sari et al., 2012)

The Tumoral marker CA 25 level usually used for screen of recurrent pathology in 85% of patients especially in patients with epithelium tumor (commonest type of ovary tumors) because CA25 can demonstrate indicative activation in tumors. However, 40%-60% of treated ovary carcinoids with normal CA 25 value have been diagnosing with recurrent. (Bast et al., 2010)

Images has a good role in screen for recurrent also in the anatomic locality of suspicious recurrent. However, SLL and histopathological correlation (despite being invasive process) usually gives most accuracy in assessing of recurrent. Using FDG-Pet instead of SLL is usually effective. (Sanli et al., 2012)

Pet/CT is of great importance for oncology. FDG may be helpful it is used in primary stage of ovary cancer, in evaluation with suspicious areas or with uncertainty of lesions and detection of far organic metastatic lesions, particularly when in combination with ECT. (Sari et al., 2012)

Our study included 25 patients who have been diagnosed with ovarian cancer, received treatment and achieved complete responsiveness. All of the 25 patients had suspicious recurrence either due to elevation tumoral markings (18 patients) or suspicious clinically. 25 patients have been referred Pet/CT scan at EL-Demerdash university hospital from August 2017 to August 2018.

In our study the mean age for the included patients was52.12 + 12.77 and there was no significant relation between age and recurrence. In a study included 45 patients by Dragosavac et al the mean age for the included patients was 59.5 ± 10.0 and they reported no significance relation between age and recurrence. (Dragosavac et al., 2013)

In another study included 34 patients by sari et al the mean age of patients with recurrence was 54,6 ± 10,7 years with no significance correlating between age and recurrence. (Sari et al., 2012)

In our study CA 25 has been reporting a sensitivity of (89.47%), specificity of (83.33%), positive prediction value of (94.44%), negative prediction value of (71.43%) and accurate of (88%).

In a study conducted for the investigation of accuracy of CA 25 in prediction of recurrence ovary cancer, CA 25 has been reported with a sensitivity of 91.5%, a specificity of 84.6%, a positive prediction value of 93.1%, a negative prediction value of 81.5%, and accurate of 89.4%. (Song et al., 2013)

In Another retrospective study included 45 patients with suspicious ovary cancer recurrent syndrome only 34 patients from the 42 patients with confirming recurrence had elevated CA 25. FDG Pet/CT scan was positive in all 42 patients who were diagnosed with recurrent (Dragosavac et al., 2013)

Sari et al., 2012 in his retrospective study which included 34 patients with suspected ovarian cancer recurrence in patients with history of epithelial ovarian tumors he reported a sensitive of 96.1% specific of 100 % positive prediction value of 100%, negative prediction value of 88.9% and accurate of 97% with the same results for FDG-Pet / CT. The high accurate CA 25 in this study may be explained by the inclusion of patients with epithelial type of ovarian tumors only to which the CA 25 is a more sensitive indicator of activity than other types of ovarian malignancy.

FDG-Pet may be more useful in determination of the recurrence of patients with negativity in conventional images and elevation CA 25. In a study by Simcock et al included 56 ovarian carcinoid patients with increasing CA 25 values high than 35 U/ml, FDG-Pet/CT scan was positive in all patients except one. In our study, among 18 patients with elevation CA 25 level FDG-Pet/CT showing recurrent in 16 patients. One of the remaining two patients has been proved to be negative for recurrence by clinical and radiology following up. (Simcock et al 2006)

In our study ECT has been reported with sensitive of (73.68), specific of (83.33%), positive prediction value of (93.33%), negative prediction value of (50%) and accurate of (76%) in detecting of ovary cancer recurrence.

In a systematic review done by (charlotte et al) to discuss current Approaches and Challenges in Management of treatment Responsiveness in Ovary Cancer they reported conventional CT to have limited sensitive of 40-93% and specific of 50-98% for recurrence disease (charlotte et al 2014)

In a series of 66 patients have symptoms but normal CA 25 31% of patients with no evident diseases on CT had lesions present on Pet/CT (Bhosale et al 2010)

In another series of 136 studies, 97 (71%) studies had residue disease and 39 (29%) study were disease free on the basis of the latest diagnosis. FDG Pet/CT and ECT had a sensitivity, specificity, negative prediction value, positive prediction value, and accuracy of 96 versus 84%, 92 versus 59%, 90 versus 59%, 97 versus 84%, and 95 versus 76%, respectively. FDG Pet/CT was more sensitive, specific, and accurate in comparison with ECT. (Tawakol et al., 2016)

In a study included Fifteen women with ovarian cancer and suspicion peritoneum carcinomatosis went DCT, MRI, and FDG Pet/CT. the study reported detection of peritoneum carcinomatosis in 10 patients. According to this study detector CT, MR, and FDG Pet/CT had a sensitivity of 96%, 98%, and 95%, and specificity was 92%, 84%, and 96%, respectively. In our study FDG Pet /CT has reported higher sensitivity in detection of peritoneum depositions than DCT, it detected peritoneum depositions in 5 patients more than DCT. The difference may be related to small sampling size in the other study also to the type of patient who already have diagnosis with primary ovary cancer and had a large peritoneum lesion which insinuate the value of Pet/CT that is believed to have more availability in detection the smaller lesion not identified by DCT. (Schmidt et al., 2015)

In our study Pet/ CT had a sensitive of (94.74%), specific of (100%), positive prediction value of (100%), negative prediction value of (85.71%) and accuracy of (96%) in detection of ovary cancer recurrence.

Thrall et al conducted a retrospective chart review of 29 ovarian cancer patients who had in conclusion CT scans and a rising CA25 level and reported a sensitivity of 94.5%, a specificity of 100% for Pet/CT in identification of recurrence syndromes and more precise localization versus CT scan alone. (Thrall et al., 2007)

In a study has 48 patients with suspicious ovary cancer recurrent went Pet/CT and then following up for 25 months 38 out of 48 (79%) patients showed pathologic areas on Pet/CT. One FDG-Pet/CT was false positivity and one was false negativity. We reported one false negativity result of Pet/CT with no false positivity (Carolin et al., 2014)

In a study included 55 patients the prognosis value of PET/CT was compared to SLL in patients went reductive surgery and received chemotherapeutics for advance ovary cancer. The study reported no significance in difference between PET/CT and SLL. (kim et al., 2004)

In a study included 44 female patients with suspicion of ovary cancer recurrent they investigated the accurate Pet/CT in detecting and restaging of recurrence ovary cancer. The sensitivity, specificity, accuracy, PPV and NPV of Pet/CT were reported 91%, 76%, 96%, 50% and 87% respectively. The low sensitive and specific Pet /CT in this study may be contributed to the larger number of patients than the number we investigated in our study. (Hetta et al., 2017)

In another series of 52 patients with suspicion of recurrence, 40 patients with a Pet-CT scan with suggestion of uptake went surgery. Of the 40 patients who went a secondary reductive surgical intervention., 38 had histopathological confirming of recurrent. Pet-CT detected a total of 86 lesions. The overall lesion-based sensitivity of Pet-CT was 90%, specificity 66.7%, positive prediction value being 83.7% and negative prediction value 77.7% and the overall accurate being 81.9%. Th measures are lesion based compared to histopathology not patient based, that may explain the lower accuracy of PET/CT in this study. (Batra et al., 2016)

In retrospective study included 45 patients with suspicion of recurrent Pet/CT has been reporting to have 100% sensitive and 100% specific. FDG Pet/CT scan was positive in all 42 patients who were confirming to have recurrent of disease and was negative in 3 patients, free from disease during following-up. (Dragosavac et al., 2013)

In a series of 39 patients with suspicion of ovary cancer recurrent either clinically, radiology or due to raised CA 25 (Gouhar et al) reported Pet/CT sensitivity of 97%, specificity of 75% and accuracy of 95%. (Gouhar et al., 2013)

According to our results, FDG-Pet/CT is found useful in ovarian cancer especially in the patients with elevated CA-25 level and negative conventional imaging. FDG-Pet/CT may be also useful in the patients with normal CA 25 level and suspicion of clinical findings for recurrence. Although there was no evidence for distance metastases outside the abdominal area in our study, FDG-Pet/CT is useful in the detection of distance metastases because it can provide whole scan.

Limitations of the study

There was some limitation in our study:

• It was a retrospective study.
• The study didn’t represent all the population (only included patients who referred to ElDemerdash hospital)
• The relatively smaller sample size comparing to other studies on the same topic.
• We used clinical and imaging follow-up in the majority of cases and histopathology was not available in most of cases.
• Some cases didn’t follow up for enough period of time (3 months).
• Serial measures of CA 25 for our patients were not available, we used only the latest CA 25 measure before the PET/CT scan.

Summary

Ovarian cancer is the second most common gynecology malignancy (after cervix cancer), with risk of 1.7%. Up to 75% of the treated patients with advance disease presenting with recurrent within two years.

CT and MRI are usually the commonly used imaging techniques in patients with suspicion of recurrent cancer. Pet scan opened new era in oncology imaging. Originally, Pet have no anatomy information. Integration of Pet/CT acquiring both metabolism and anatomy images data by usage a device and provides precisely anatomy localization of suspicious spots of FDG.

Our study included 25 patients who have been diagnosed with ovarian cancer, received treatment and achieving complete response. All of the 25 patients had suspected recurrence either due to elevated tumor markers or suspicious clinical findings. The 25 patients have been referred for Pet/CT scan at ELDemerdash university hospital from July 2017 to August 2018.

All patients went ECT scan as a part of the Pet/CT scan. ECT images were interpreted first, then fusion Pet/CT images. Some patients were proved to have recurrent by histopathology and the rest of the patients were followed up for a time period of 3 to 6 months. 19 patients out of the 25 patients were diagnosed with recurrence ovary cancer.

In our study Pet/CT had a higher sensitivity, specific and accuracy than ECT alone and also higher than CA25 in detection of recurrence ovary cancer.

Conclusion

According to our study results we concluded that:

FDG-Pet/CT is a useful imaging tool in patients with suspicious ovary cancer recurrence especially in patients with elevation of CA 25 level and negative conventional images.

FDG-Pet/CT may be also useful in the patients with normal CA-25 level and suspicious clinically findings for recurrence.