Annals of Surgical Oncology Cite Track
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Hendren, S. K.
Right arrow Articles by Fraker, D. L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Hendren, S. K.
Right arrow Articles by Fraker, D. L.
Annals of Surgical Oncology 8:65-71 (2001)
© 2001 Society of Surgical Oncology

ORIGINAL ARTICLES

Phase II Trial of Debulking Surgery and Photodynamic Therapy for Disseminated Intraperitoneal Tumors

Samantha K. Hendren, MD, Stephen M. Hahn, MD, Francis R. Spitz, MD, Todd W. Bauer, MD, Stephen C. Rubin, MD, Timothy Zhu, PhD, Eli Glatstein, MD and Douglas L. Fraker, MD

From the Departments of Surgery (SKH, FRS, TWB, DLF) , Radiation Oncology (SMH, TZ, EG), and Obstetrics and Gynecology (SCR), University of Pennsylvania, Philadelphia, Pennsylvania.

Correspondence: Address correspondence and reprint requests to Dr. Douglas L. Fraker, University of Pennsylvania Department of Surgery, 3400 Spruce Street, 4 Silverstein, Philadelphia, PA 19104; Fax: 215- 614-0765.


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 CONCLUSIONS
 REFERENCES
 
BACKGROUND: Photodynamic therapy (PDT) combines photosensitizer drug, oxygen, and laser light to kill tumor cells on surfaces. This is the initial report of our phase II trial, designed to evaluate the effectiveness of surgical debulking and PDT in carcinomatosis and sarcomatosis.

METHODS: Fifty-six patients were enrolled between April 1997 and January 2000. Patients were given Photofrin (2.5 mg/kg) intravenously 2 days before tumor-debulking surgery. Laser light was delivered to all peritoneal surfaces. Patients were followed with CT scans and laparoscopy to evaluate responses to treatment.

RESULTS: Forty-two patients were adequately debulked at surgery; these comprise the treatment group. There were 14 GI malignancies, 12 ovarian cancers and 15 sarcomas. Actuarial median survival was 21 months. Median time to recurrence was 3 months (range, 1–21 months). The most common serious toxicities were anemia (38%), liver function test (LFT) abnormalities (26%), and gastrointestinal toxicities(19%), and one patient died.

CONCLUSIONS: Photofrin PDT for carcinomatosis has been successfully administered to 42 patients, with acceptable toxicity. The median survival of 21 months exceeds our expectations; however, the relative contribution of surgical resection versus PDT is unknown. Deficiencies in photosensitizer delivery, tissue oxygenation, or laser light distribution leading to recurrences may be addressed through the future use of new photosensitizers.

Key Words: Photodynamic therapy— • Carcinomatosis— • Sarcomatosis— • Photofrin— • Ovarian cancer.


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
MATERIALS AND METHODS
 RESULTS
 CONCLUSIONS
 REFERENCES
 
Disseminated intraperitoneal tumor is a pattern of disease spread in gastrointestinal malignancies, ovarian cancers and sarcomas that often occurs in the absence of lymphatic or hematogenous metastases.1,2 This disease often affects relatively young patients, but there is no established, curative therapy available. Systemic chemotherapy has a limited effect on this disease, and radiotherapy is not a viable option, because it would be necessary to treat the entire abdominal cavity, and toxicity would be excessive. Surgical resection alone is destined to fail because all peritoneal surfaces are contaminated with tumor. Even aggressive peritonectomy procedures leave large areas of the abdominal cavity untreated, including the capsules of the spleen and liver and the bowel serosa.3 In ongoing clinical trials, aggressive surgical debulking has been combined with either intraperitoneal chemotherapy, immunotherapy, or hyperthermic peritoneal perfusion in an attempt to control this condition.

Photodynamic therapy (PDT) is a novel anticancer treatment that combines photosensitizer drug, oxygen, and laser light to kill tumor cells on surfaces.4,5 The most common photosensitizer agent currently in use is Photofrin, a purified form of hematoporphyrin derivative (HPD). Its mechanism of action is the formation of oxygen free radical compounds after activation by a particular wavelength of light, resulting in direct cytotoxicity and microvascular damage.6 The ideal photosensitizer localizes to tumor tissue in higher concentrations than in nearby normal tissues, and preclinical research with HPD and Photofrin has shown tumor localization of these compounds.7 Although the photosensitizer drug is administered systemically, the cytotoxic effect is limited to those tissues exposed to the activating light dose. The depth of penetration varies with the wavelength of light, but usually is in the range of a few millimeters. Thus, PDT theoretically is an ideal therapy for the peritoneal surface disease that characterizes carcinomatosis and sarcomatosis. This therapy has been approved by the Food and Drug Administration (FDA) for treatment of obstructing esophageal and lung cancers, and is under study in cutaneous, bladder, pleural, and head and neck cancers, all of which are surface malignancies.

In the mid-1980s, preclinical work using Photofrin PDT in a mouse ovarian teratoma model of carcinomatosis resulted in cures of the otherwise lethal cancer.8,9 Based on this preclinical work and toxicity studies in large animals, a Phase I trial at the National Cancer Institute enrolled 54 human patients with carcinomatosis and sarcomatosis.10,11 Using escalating light and drug dosing, the dose-limiting toxicities were found to be bowel perforation and fistula formation. Laser wavelength and light and drug dose modifications, particularly in treating the bowel, resulted in acceptable toxicity. Although this Phase I trial was not designed to determine effectiveness, the patient outcomes were extremely suggestive of therapeutic benefit, with over 60% survival at 3 years and at least four patients with prolonged disease-free survival. This is the initial report of our phase II trial utilizing the maximal tolerated doses of photosensitizer and light defined in the Phase I trial, designed to evaluate the effectiveness of PDT in patients with carcinomatosis or sarcomatosis.


   MATERIALS AND METHODS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
 CONCLUSIONS
 REFERENCES
 
Patient Selection
Fifty-six patients were enrolled in the trial between April 1997 and January 2000. Criteria for patient selection are outlined in Table 1. Patients with all tumor histologies and previous therapies were eligible for the trial, as long as there was no evidence of disease outside the peritoneal cavity or hematogenous liver disease. This was confirmed with clinical evaluation and CT scanning of the chest, abdomen, and pelvis or equivalent three-dimensional imaging. This trial was approved by the Institutional Review Board of the University of Pennsylvania, the Clinical Trials Scientific Review and Monitoring Committee of the University of Pennsylvania, and the United States Food and Drug Administration. All participating patients provided informed consent.


View this table:
[in this window]
[in a new window]
  		Table 1. Patient selection criteria
 
Treatment Protocol
The first step in patient treatment was intravenous administration of 2.5 mg/kg of Photofrin (QLT Phototherapeutics Ltd., Vancouver, British Columbia, Canada) 2 days before scheduled laparotomy. After drug administration, patients were instructed to avoid exposure to sunlight or non-fluorescent artificial light for 4 to 6 weeks. Before surgery, the operating room (OR) lights were covered with filters to prevent burning of exposed patient tissues, and the operating team was equipped with filtering glasses to be worn during laser light administration.

At laparotomy, tumor was debulked to a thickness of 5 mm or less. Organ resections required to achieve this debulking were performed, although nodules were resected from organ surfaces where feasible. Peritoneal stripping was performed as needed to remove gross tumor nodules but was not performed for microscopic disease. Complete lysis of adhesions was required to allow light delivery to all surfaces and to remove all gross disease wherever possible. Patients without diffuse carcinomatosis or patients whose tumors could not be debulked to 5 mm maximal tumor thickness did not receive laser light treatment and were considered to be off study.

Laser light was delivered to all peritoneal surfaces by the radiation oncology and physics staff using defined doses and wavelengths from the Phase I trial. First, 532-nanometer (nm) wavelength (green) light was administered to the small bowel, bowel mesentery, and colon in segments at a dose (fluence) of 2.5 J/cm2 using a flat-cut optical fiber (Laserscope Inc., San Jose, CA) suspended over the operating table. The light dose was monitored using a mobile photodiode held over the treatment area. Then the other peritoneal surfaces were treated with 630-nm (red) laser light delivered with a fiber enclosed in an intralipid-filled, modified endotracheal tube. The peritoneum also was filled with a solution of 0.01% intralipid containing calcium and magnesium, and the endotracheal tube was submerged within the solution. Care was taken to avoid contamination of the solution with blood, because this results in absorption of the laser light and reduction in the delivered dose rate. Five temporarily implanted photodiodes and one mobile photodiode were used to measure the light dose delivered to each peritoneal region. The fluences used for each area of the peritoneum were as follows: stomach, 5 J/cm2; diaphragms, liver, and spleen, 7.5 J/cm2; and pelvis and peritoneal gutters, 10 J/cm2. Focal areas of the peritoneum with severe tumor involvement were treated with "boost" doses of 630-nm laser light. The laser equipment used consisted of a KTP/532 Laser System and a 630 x P Dye Module (Laserscope Inc., San Jose, CA).

After light treatment, the abdomen was copiously irrigated. Bowel anastomoses (if necessary) were performed at that time, and closure was completed. Postoperative care consisted of admission to the intensive care unit and close hemodynamic monitoring, with resuscitation as required. Perioperative toxicity was monitored using the National Cancer Institute (NCI) Cooperative Group Common Toxicity Criteria. Some delayed toxicities, such as small bowel obstruction and hydronephrosis, also were included in the toxicity analysis, especially if the toxicity necessitated readmission.

Patient Follow-up and Statistical Analysis
Patients were followed with clinical exams, computed tomography (CT) scans, and laparoscopy to evaluate responses to treatment. Patient follow-up visits were scheduled for 1 month and 3 months postoperatively, and every 3 months thereafter. CT scans were performed every 3 months, and laparoscopic evaluation was offered at the 6-month follow-up to every patient who was CT scan-negative for recurrence. Patients were considered "off study" at the time of radiographic or biopsy-proven recurrence, and alternative therapies were allowed thereafter. Retreatment with the PDT protocol was allowed for three patients who developed recurrences after a long disease-free interval. Only the first treatment of these retreated patients was included in this toxicity and outcome analysis. Time to recurrence and survival were analyzed using Kaplan-Meier survival curves. A Kaplan-Meier survival curve also was constructed comparing patients who had all gross disease resected versus those with residual gross disease before light therapy.


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
CONCLUSIONS
 REFERENCES
 
Patient Demographics
Fifty-six patients were entered into the trial between April 1997 and January 2000. Forty-three were able to be completely debulked and received laser light activation. Of this group, one patient’s final pathology was negative for malignancy and consisted of bulky fibrosis that was benign; this patient was excluded from the treatment group for purposes of further analysis. The thirteen patients who did not undergo the full therapy included seven women and six men with the following histologies: six gastrointestinal (GI) cancers, three sarcomas, and four ovarian cancers. The reasons for exclusion from treatment were as follows: tumor unable to be debulked (ten patients); unsuspected liver metastasis (one patient); and only locally recurrent disease found at laparotomy (two patients).

The 42 patients who made up the treatment group are the focus of the following results. The average age of the treatment group was 48.8 years (range, 21–70 years). The gender distribution was 30 women and 12 men. Ninety-five percent had previous surgical resection, and over 60% had previous chemotherapy (data not shown). The histologies of the treatment group are displayed in detail in Table 2. When available, the pathology reports from the patients’ initial surgical resection (often at another institution) were reviewed by our pathologists, and these results are shown. In several cases, the pathology report from our surgical resection was used. Fourteen patients had GI malignancies (colon [6 patients], appendiceal mucinous adenocarcinoma with malignant features [3 patients], gastric [2 patients], pseudomyxoma peritonei [1 patient], 1 poorly-differentiated carcinoma of unknown primary [1 patient], and adenocarcinoid [1 patient]), 12 patients had ovarian cancers, 15 patients had sarcomas. and 1 patient had peritoneal malignant mesothelioma.


View this table:
[in this window]
[in a new window]
  		Table 2. Tumor histologies of the treatmentgroup
 
Surgical Procedures Performed
The surgical procedures included a complete lysis of adhesions for all patients, plus a variety of organ resections to remove all gross disease. The organ resections performed are presented by percentage of patients affected in Fig.1. Peritoneal stripping was performed only where required to remove gross tumor nodules. When possible, all gross disease was resected.



View larger version (17K):
[in this window]
[in a new window]
  		FIG. 1. Organ resections performed during debulking laparotomy in our treatment group, expressed as percentage of patients affected.

 
Outcomes
The median time since treatment (follow-up) is 18.5 months, and median survival has not been established, because 57% of patients are alive to date. Kaplan-Meier curves depicting the overall survival and survival by histologic group are shown in Fig. 2. Median actuarial survival is 21 months for all groups combined, with a trend toward longest survival in ovarian cancer and shortest in gastrointestinal cancers. The difference between broad histologic groups is not statistically significant. Recurrence data are depicted in Fig. 3. As shown, most patients have early evidence of recurrence by CT scan or laparoscopy, although many remain clinically well.



View larger version (25K):
[in this window]
[in a new window]
  		FIG. 2. Kaplan-Meier curves of fractional patient survival over time in our treatment group overall (A) and in each broad histologic group (B).

 


View larger version (24K):
[in this window]
[in a new window]
  		FIG. 3. Kaplan-Meier curves of overall time to recurrence in the treatment group overall (A) and in each broad histologic group (B).

 
We qualitatively reviewed the outcome data to determine whether the pattern of disease (fewer or more numerous nodules or size of nodules), the number of organs involved, or completeness of surgical resection influenced the likelihood of a poorer outcome. Although there was no obvious association with regard to pattern of disease or organ resection, the inability to be debulked to the absence of gross disease is associated with poorer survival. In the group of patients who have died thus far, 89% were unable to be resected free of all gross disease. A Kaplan-Meier curve was used to plot the survival of the patients completely resected free of gross disease versus those with thin residual gross disease prior to light treatment. The patients who were completely resected before receiving PDT have a significantly better actuarial survival compared to patients who were incompletely resected ( Fig. 4).



View larger version (18K):
[in this window]
[in a new window]
  		FIG. 4. Kaplan-Meier curve of survival comparing patients completely resected versus patients incompletely resected. This graph depicts the fraction of surviving treatment group patients over time divided into those patients completely resected free of gross disease vs. those patients unable to be completely resected free of all gross disease.

 
Toxicity
Toxicity data are presented in Table 3. The most common serious (NCI Common Toxicity Criteria Grade 3–5) toxicities were anemia (38% of patients), transient LFT abnormalities (26%), and bowel obstruction or other GI abnormalities (19%). One patient died from a myocardial infarction early in our trial. One patient had a serious pulmonary embolism, three patients developed intra-abdominal abscesses, and two patients developed fistulae. There were no bowel perforations, although this was the primary dose-limiting toxicity in the Phase I trial. Patients required shielding from sunlight for 4 to 6 weeks due to residual photosensitizer effects; however, no serious skin toxicities occurred in follow-up. All patients developed the capillary leak syndrome perioperatively, characterized by a body weight gain of 15% to 20% and requiring intensive care management and volume resuscitation. In general, this syndrome resolved over the course of 3 to 7 days.


View this table:
[in this window]
[in a new window]
  		Table 3. Toxicities in treatment group (n = 42)
 

   CONCLUSIONS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 CONCLUSIONS
REFERENCES
 
Meaningful treatment options are extremely limited for patients with disseminated intraperitoneal cancer. The patient population presented here is characterized by advanced disease, young age, and extensive previous treatment. For example, all but one of our ovarian cancer patients were treated in this study for recurrent carcinomatosis status-post previous debulking and chemotherapy. As can be seen from the table of treatment group histologies, only one patient in our treatment group had pseudomyxoma peritonei, which often has a very prolonged natural history. The other 41 patients in our treatment group had more aggressive histologies. The median survival of 21 months exceeds our expectations for this patient population.

Although most of these patients have recurred, many are clinically well for long intervals after therapy, and several have had prolonged disease-free survival. Our aggressive approach for identifying early recurrences, i.e., CT scans every 3 months and laparoscopy at 6 months, has contributed to our large proportion of early recurrences. For example, one patient with colon cancer had peritoneal implants smaller than 5 mm at 6-month laparoscopy, but at 26 months of follow-up is still clinically well. Nonetheless, this patient is counted as a 6-month recurrence.

The toxicity profile of our treated patients compares favorably with the toxicities seen from extensive debulking procedures in general and other experimental treatments for carcinomatosis in particular.2,3 The most common serious toxicities were anemia, transient LFT abnormalities, and bowel obstruction or other GI abnormalities. The one treatment death occurred in one of our earliest patients due to an acute myocardial infarction. Thereafter, with aggressive pretreatment cardiac screening, our cardiovascular morbidity has been minimal. Many of our toxicities can be related directly to the organ resections performed or to the underlying diagnosis of malignancy, such as the incidence of DVT, PE, diarrhea, and transient metabolic and hemodynamic abnormalities.

The toxicities that can be attributed specifically to the photodynamic therapy include (1) the capillary leak syndrome, with its attendant perioperative requirement for volume resuscitation and (2) the elevated frequency of hydronephrosis, which may be due to retroperitoneal scarring from the therapy. It is worth noting that there were no bowel perforations, given that this was the primary dose-limiting toxicity in the Phase I trial, although there were two fistulas. It is also worth commenting that no serious skin toxicities have occurred in follow-up, despite the long half-life of our current photosensitizer agent.

The obvious limitation in interpretation of these data is the lack of a debulking-only control group. Unfortunately, we must rely on historical data in order to determine whether our survival exceeds that expected for this population of patients. Limited data are available regarding this patient population, partly because debulking surgery is not routinely performed except in ovarian cancer, and partly because this patient population has an extremely heterogeneous natural history. Several recent studies focusing on carcinomatosis from gastrointestinal primaries have attempted to characterize the natural history of this disease.1,2 Medial survivals of 3.1 to 6.7 months were reported for patients with carcinomatosis, but some patients with hematogenous metastases were included in these analyses. Our patient population is exceedingly heterogeneous due to the open enrollment criteria for this trial, and future reports likely will focus on subgroup analysis in an effort to direct this therapy to those patients most likely to benefit. These early data reveal an association between the ability to be completely resected free of gross disease and survival, but it fails to reveal a survival advantage for any broad histologic group.

So far, our outcome analysis has focused on disease-free interval and survival; however, these may not be the most appropriate outcome measures for our patient population. Although we have not yet formally evaluated PDT as a palliative therapy, many of our patients have experienced an improved quality of life after hospital discharge, in terms of gastrointestinal function, resolution of ascites, improved energy level, and overall sense of well being. Obviously the toxicity of the procedure must be weighed against the benefits observed, and a formal evaluation of non-survival outcomes should be undertaken.

Several other trials are underway using local therapies for disseminated intraperitoneal cancer.3,12–16 Investigators conducting trials with hyperthermic peritoneal perfusion, radical peritonectomy, intraperitoneal chemotherapy, and intraperitoneal immunotherapy also are approaching carcinomatosis and sarcomatosis as a "surface problem." Loggie and colleagues recently have reported the results of mitomycin C hyperthermic peritoneal perfusion following surgical debulking in 84 patients with gastrointestinal carcinomatosis.16 Their results are remarkably similar to ours; they found an overall median survival of 14.3 months and improved survival in those patients able to be completely resected. These encouraging results validate the surgical oncology community’s ongoing efforts to aggressively treat carcinomatosis with surface modalities.

In summary, Photofrin PDT for carcinomatosis has been successfully administered to 42 patients in our phase II trial, with acceptable toxicity. The median survival of 21 months exceeds our expectations, given the aggressive diseases of our patient population; however, the relative contribution of surgical resection versus photodynamic therapy is unknown. Disease recurrences may be due to deficiencies in photosensitizer delivery or localization, tissue oxygenation, or laser light distribution. Ongoing research in the preclinical setting is addressing these issues with new, "second generation" photosensitizer agents. These agents will have a shorter half-life and better tumor localization, potentially overcoming our current limitations.


   Acknowledgments
 
We thank Debbie Smith, the clinical nurse coordinator for PDT trials at Penn. We also are indebted to the Department of Physics team, including Arjun Yodh and Teador Vulcan, as well as to Carmen Rodriguez, our technical laser expert. Finally, we thank Rosemarie Mick for sharing her statistical expertise. This trial was sponsored by the National Institutes of Health and supported in part by the Georgene S. Harmelin Endowment Fund.


   Footnotes
 
Presented at the 53rd Annual Meeting of the Society of Surgical Oncology, New Orleans, Louisiana, March 16-19, 2000.

Received for publication May 23, 2000. Accepted for publication August 18, 2000.


   REFERENCES
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 CONCLUSIONS
 REFERENCES
 

  1. Sadeghi B, Arvieux C, Glehen O, et al. Peritoneal carcinomatosis from non-gynecologic malignancies. Cancer 2000; 88: 358–63.[CrossRef][Medline]
  2. Rosen SA, Buell JF, Yoshida A, et al. Initial presentation with stage IV colorectal cancer: how aggressive should we be? Arch Surg 2000; 135: 530–4.[Abstract/Free Full Text]
  3. Sugarbaker PH, Jablonski KA. Prognostic features of 51 colorectal and 130 appendiceal cancer patients with peritoneal carcinomatosis treated by cytoreductive surgery and intraperitoneal chemotherapy. Ann Surg 1995; 221: 124–32.[Medline]
  4. Dougherty TJ, Gomer DJ, Henderson BW, et al. Photodynamic therapy. J Natl Cancer Inst 1998; 90: 889–905.[Abstract/Free Full Text]
  5. Fisher AMR, Murphree AL, Gomer CJ. Clinical and preclinical photodynamic therapy. Lasers Surg Med 1995; 17: 2–31.[Medline]
  6. Weishaupt KR, Gomer CJ, Dougherty TJ. Identification of singlet oxygen as the cytotoxic agent in photo-inactivation of a murine tumor. Cancer Res 1976; 36: 2326–9.[Medline]
  7. Gomer CJ, Dougherty TJ. Determination of [3H] and [14C] hematoporphyrin derivative distribution in malignant and normal tissue. Cancer Res 1979; 39: 146–51.[Abstract/Free Full Text]
  8. Tochner Z, Mitchell JB, Harrington FS, Smith P, Russo DT, Russo A. Treatment of murine intraperitoneal ovarian ascitic tumor with hematoporphyrin derivative and laser light. Cancer Res 1985; 45: 2983–7.[Abstract/Free Full Text]
  9. Tochner Z, Mitchell JB, Smith P, Harrington FS, Glatstein E, Russo DT, Russo A. Photodynamic therapy of ascites tumours within the peritoneal cavity. Br J Cancer 1986; 53: 733–6.[Medline]
  10. Tochner Z, Mitchell JB, Hoekstra HJ, et al. Photodynamic therapy of the canine peritoneum: normal tissue response to intraperitoneal and intravenous Photofrin followed by 630 nm light. Lasers Surg Med 1991; 11: 158–64.[Medline]
  11. DeLaney TF, Sindelar WF, Tochner Z, et al. Phase I study of debulking surgery and photodynamic therapy for disseminated intraperitoneal tumors. Int J Radiat Oncol Biol Phys 1993; 25: 445–57.[Medline]
  12. VanderMeer TJ, Callery MP, Meyers WC. The approach to the patient with single and multiple liver metastases, pulmonary metastases, and intra-abdominal metastases from colorectal carcinoma. Hematol Oncol Clin North Am 1997; 11: 759–75.[Medline]
  13. Freedman RS, Lenzi R, Kudelka AP, Lawrence DD, Rosenblum M, Platsoucas CD. Intraperitoneal immunotherapy of peritoneal carcinomatosis. Cytokines Cell Mol Ther 1998; 4: 121–40.[Medline]
  14. Hirose K, Katayama K, Iida A, Yamaguchi A, Nakagawara G, Umeda S, Kusaka Y. Efficacy of continuous hyperthermic peritoneal perfusion for the prophylaxis and treatment of peritoneal metastasis of advanced gastric cancer: evaluation by multivariate regression analysis. Oncology 1999; 57: 106–14.[CrossRef][Medline]
  15. Loggie BW, Perini M, Fleming RA, Russell GB, Geisinger KR. Treatment and prevention of malignant ascites associated with disseminated intraperitoneal malignancies by aggressive combined-modality therapy. Am Surg 1997; 63: 137–43.[Medline]
  16. Loggie BW, Fleming RA, McQuellon RP, Russell GB, Geisinger KR. Cytoreductive surgery with intraperitoneal hyperthermic chemotherapy for disseminated peritoneal cancer of gastrointestinal origin. Am Surg 2000; 66: 561–8.[Medline]



This article has been cited by other articles:


Home page
 The OncologistHome page
M. Triesscheijn, P. Baas, J. H. M. Schellens, and F. A. Stewart
Photodynamic Therapy in Oncology
Oncologist, October 1, 2006; 11(9): 1034 - 1044.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
S. M. Hahn, M. E. Putt, J. Metz, D. B. Shin, E. Rickter, C. Menon, D. Smith, E. Glatstein, D. L. Fraker, and T. M. Busch
Photofrin uptake in the tumor and normal tissues of patients receiving intraperitoneal photodynamic therapy.
Clin. Cancer Res., September 15, 2006; 12(18): 5464 - 5470.
[Abstract] [Full Text] [PDF]

Home page
 JNCI J Natl Cancer InstHome page
K. A. Cengel, S. M. Hahn, and E. Glatstein
C225 and PDT Combination Therapy for Ovarian Cancer: The Play's the Thing
J Natl Cancer Inst, October 19, 2005; 97(20): 1488 - 1489.
[Full Text] [PDF]

Home page
 JNCI J Natl Cancer InstHome page
M. G. del Carmen, I. Rizvi, Y. Chang, A. C. E. Moor, E. Oliva, M. Sherwood, B. Pogue, and T. Hasan
Synergism of Epidermal Growth Factor Receptor-Targeted Immunotherapy With Photodynamic Treatment of Ovarian Cancer In Vivo
J Natl Cancer Inst, October 19, 2005; 97(20): 1516 - 1524.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
T. M. Busch, S. M. Hahn, E. P. Wileyto, C. J. Koch, D. L. Fraker, P. Zhang, M. Putt, K. Gleason, D. B. Shin, M. J. Emanuele, et al.
Hypoxia and Photofrin Uptake in the Intraperitoneal Carcinomatosis and Sarcomatosis of Photodynamic Therapy Patients
Clin. Cancer Res., July 15, 2004; 10(14): 4630 - 4638.
[Abstract] [Full Text] [PDF]

Home page
 Ann. Thorac. Surg.Home page
V. R. Litle, N. A. Christie, H. C. Fernando, P. O. Buenaventura, P. F. Ferson, and J. D. Luketich
Photodynamic therapy for endobronchial metastases from nonbronchogenic primaries
Ann. Thorac. Surg., August 1, 2003; 76(2): 370 - 375.
[Abstract] [Full Text] [PDF]

Home page
 Ann. Surg. Oncol.Home page
R. J. Canter, R. Mick, S. B. Kesmodel, D. J. Raz, F. R. Spitz, J. M. Metz, E. J. Glatstein, S. M. Hahn, and D. L. Fraker
Intraperitoneal Photodynamic Therapy Causes a Capillary-Leak Syndrome
Ann. Surg. Oncol., June 1, 2003; 10(5): 514 - 524.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
O. Glehen, F. Mithieux, D. Osinsky, A.C. Beaujard, G. Freyer, Ph. Guertsch, Y. Francois, P. Peyrat, G. Panteix, J. Vignal, et al.
Surgery Combined With Peritonectomy Procedures and Intraperitoneal Chemohyperthermia in Abdominal Cancers With Peritoneal Carcinomatosis: A Phase II Study
J. Clin. Oncol., March 1, 2003; 21(5): 799 - 806.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
C. Menon, S. N. Kutney, S. C. Lehr, S. K. Hendren, T. M. Busch, S. M. Hahn, and D. L. Fraker
Vascularity and Uptake of Photosensitizer in Small Human Tumor Nodules: Implications for Intraperitoneal Photodynamic Therapy
Clin. Cancer Res., December 1, 2001; 7(12): 3904 - 3911.
[Abstract] [Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Hendren, S. K.
Right arrow Articles by Fraker, D. L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Hendren, S. K.
Right arrow Articles by Fraker, D. L.

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS