Unfortunately, as is common with uterine cancer, by the time it was discovered, the disease was at Stage 4, which implies a low survival rate.  She had surgery on April 1, 2016, to remove the noticeable large and small tumors, but the surgeon estimated that he had removed about 95% of the cancer.  Following chemotherapy with paclitaxel and carboplatin was supposed to take care of the rest, but it only made Dianne very ill and seemed not to halt the growth of further metastases.  After four rounds of this treatment led to severe anemia, she had two more rounds of paclitaxel and avastin, and that combination seemed more tolerable, though it was not notably effective. In November 2016 she enrolled in a newly-opened immunotherapy trial that attacked the PD-1/PD-L1 mechanism that cancers use to hold off the immune system, and we had great hope that this new type of therapy would work, as we know similar approaches had done in the case of others we knew.  In fact, she felt well during this time, and we were able to travel to Los Angeles for a brief vacation.  Alas, some yet-unknown features of the cancer or Dianne’s genetics failed to prevent disease progression, and she “flunked out” of the trial in February 2017.  She was receiving further chemotherapy with doxyl and avastin after that, as a temporizing measure with the hope that some new experimental therapy trials would become available in time, but that was not the case.  By mid-June, her oncologist gave up and persuaded her to enter hospice care at home, which she did. She developed pulmonary congestion and died just after midnight on July 4, 2017.

She had complained of abdominal pain as early as the summer of 2015, but a gastroenterologist to whom she was referred diagnosed it as inflammatory bowel disease, and not serious.  She persuaded her internist eventually (March, 2017) to order a uterine biopsy, whose results were reported as clear-cell carcinoma, which has very poor prognosis.  Pathology follow-up at Mass General after her surgery instead concluded that her tumors were a mix of uterine carcinosarcoma and endometreoid adenocarcinoma. Although the second of these is often successfully treatable, the first is not often responsive to therapy. A Foundation Medicine analysis of mutations in her tumors identified only two mutations, in TP53 and CREBBP, but had no suggestions for treatments that could exploit these particular variants.

The tragic outcome of Dianne’s course reminds us of the dismal state of medical knowledge about the genesis of cancer, choice of optimal care, and the sources of variation in different patients’ responses to therapy.